Patent Publication Number: US-11041207-B2

Title: Method for predicting a subject&#39;s response to valproic acid therapy

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application is a continuation in part of PCT international application No. PCT/US2016/061654, filed Nov. 11, 2016, which claims priority to U.S. Provisional Patent Application No. 62/255,145 filed on Nov. 13, 2015. The entire contents of the aforementioned application is incorporated by reference as if recited in full herein. 
    
    
     GOVERNMENT FUNDING 
     This invention was made with government support under grants R21MH0706019, R21MH082331, R01MH100219, UL1TR000038, and KL2RR024157 from the National Institutes of Health. The government has certain rights in the invention. 
    
    
     FIELD OF THE INVENTION 
     The present invention provides, inter alia, methods for treating or ameliorating the effects of a disorder, such as schizophrenia or bipolar disorder, in a subject. Methods and diagnostic systems for identifying subjects with such a disorder, and for predicting clinical response to treatments of such disorders, are also provided herein. 
     BACKGROUND OF THE INVENTION 
     Negative symptoms, including avolition, blunted affect and social withdrawal, are amongst the most persistent and debilitating in schizophrenia, and are largely unaddressed by current medications (Blanchard et al., 2011). Negative symptoms, which are present across psychiatric disorders (Lindenmayer et al., 2008; Fernandez-Garcimartin et al., 2014), contribute significantly to the huge personal and economic costs of severe psychiatric illness and other disorders. 
     Proline is a precursor of the neurotransmitter glutamate and may function as a central nervous system (CNS) neuromodulator (Phang et al., 2001; and references therein). Peripheral hyperprolinemia, which reflects CNS proline elevation (Dingman and Sporn, 1959; Efrom, 1965; Baxter et al., 1985; Gogos et al., 1999; Paterlini et al., 2005; Luykx et al., 2015), has been associated with psychiatric disorders including schizophrenia (Tomiya et al., 2007; Clelland et al., 2011; Orešič et al., 2011). The proline dehydrogenase gene (PRODH) encodes proline oxidase (PDX), the enzyme that catalyzes the first step in proline catabolism. The direct consequences of elevated proline for neurotransmission have been demonstrated by work on the hyperprolinemic Prodh null model (Gogos et al., 1999; Paterlini et al., 2005). In the presence of PDX deficiency and elevated proline (peripheral and CNS), the mouse exhibits altered glutamate and dopamine (DA) signaling, including an enhancement of glutamatergic synaptic transmission, prefrontal DA transmission, and functional hyper-DA responses (Paterlini et al., 2005). 
     PRODH maps to chromosome 22q11, a region associated with the highest known genetic risk for schizophrenia, aside from that shared by monozygotic twins. In addition, this location is also associated with the hemizygous microdeletion found in 22q11 deletion syndrome (22q11DS), and there is an increased risk of schizophrenia as well as other psychotic, mood-, obsessive compulsive-, and autism spectrum disorders in 22q11DS patients (Karayiorgou et al., 2010; Baker and Skuse, 2005; Fine et al., 2005; Gothelf et al., 2004). Approximately 37-50% of 22q11DS patients have significant elevation of fasting plasma proline, and proline levels inversely correlate with intelligence quotient in 22q11DS (Raux et al., 2007). 
     The catechol-O-methyltransferase gene (COMT) encodes the eponymous enzyme that methylates and inactivates catecholamines including DA, and also maps to 22q11, distal to PRODH. The COMTVal 158 Met functional polymorphism (substitution of valine (Val) to methionine (Met) at residue 158), has been studied with regards to DA neurotransmission because Val/Val homozygotes have pre-frontal cortex (PFC) enzyme activity approximately 40% higher than Met/Met homozygotes and are considered to have concomitant lower PFC DA levels (Lachman et al., 1996; Chen et al., 2004). It has thus been suggested that the Val 158 Met polymorphism modulates cognitive functioning (Bilder et al., 2004; and references therein). Whilst COMT has been associated with psychotic and mood disorders including schizophrenia and bipolar disorder (Shifman et al., 2002; Shifman et al., 2004), results have been inconsistent (Allen et al., 2008). 
     A CNS functional interaction between COMT and PRODH has been proposed by Paterlini et al. (2005), who suggested that significant cortical Comt upregulation in the Prodh null mouse represents a compensatory response to increased PFC DA transmission, arising as a consequence of PRODH deficiency enhancing glutamatergic synaptic transmission. In addition, high levels of plasma proline in 22q11DS with the low activity Met allele have been associated with psychosis with positive symptoms (Raux et al., 2007), and significantly decreased smooth pursuit eye movement (SPEM) (Vorstman et al., 2009). 
     Recent reports have shown significantly elevated fasting peripheral proline in schizophrenia patients versus healthy controls (Clelland et al., 2011). Given the finding of increased COMT expression in the Prodh null mouse (Paterlini et al., 2005), and the significant interaction between proline and COMT genotype on psychosis risk in 22q11DS patients (Raux et al., 2007), this data suggests that COMT genotype and proline levels could be employed for treatment decisions for schizophrenia and other psychiatric disorders. 
     SUMMARY OF THE INVENTION 
     The present invention provides a method for predicting the clinical response of a subject with a disorder to a proline modulator comprising:
         a) obtaining a biological sample from the subject;   b) determining the identity of the allele(s) of the Val 158 Met locus associated with the COMT gene in the sample;   wherein the presence of Val/Val is indicative of a subject who will benefit from an agent that increases proline levels, and wherein the presence of at least one Met allele is indicative of a subject who will benefit from an agent that decreases proline levels; and   c) administering, if appropriate based on the results of step b), an effective amount of a proline modulator to the subject to achieve an appropriate clinical response.       

     The present invention also provides a method for monitoring the treatment of a subject in need thereof, the method comprising:
         a) obtaining a biological sample from the subject;   b) determining the genotype for the allele(s) of the COMT gene at amino acid position 158 in the biological sample;   c) determining the subject&#39;s proline level; and   d) modifying the course of treatment, if necessary, including administering a different proline modulator to the subject, or stopping or omitting treatment with a proline modulator, based upon the presence or absence of a Val 158 Met polymorphism in the COMT gene, and/or an increase or decrease in the subject&#39;s proline level.       

     The present invention also provides a diagnostic system for identifying a subject with a disorder who will benefit from an agent that increases or decreases proline levels comprising:
         a) obtaining a biological sample from the subject; and   b) determining the identity of alleles of the Val 158 Met locus associated with the COMT gene in the sample;   wherein the presence of ValNal is indicative of a subject who will benefit from an agent that increases proline levels and wherein the presence of at least one Met allele is indicative of a subject who will benefit from an agent that decreases proline levels. Kits comprising the diagnostic systems of the present invention packaged together with instructions for use are also provided.       

     The present invention also provides a method for predicting the clinical response of a subject with a disorder to a proline modulator comprising:
         a) determining the identity of the allele(s) of the Val 158 Met locus associated with the COMT gene using a biological sample of the subject;   wherein the presence of ValNal at the locus is indicative of a subject who will benefit from an agent that increases proline levels, and wherein the presence of at least one Met allele at the locus is indicative of a subject who will benefit from an agent that decreases proline levels; and   b) administering, if appropriate based on the results of step (a), an effective amount of a proline modulator to the subject to achieve a clinically appropriate response.       

     The present invention also provides a method for monitoring the treatment of a subject with a disorder, the method comprising:
         a) determining the genotype for the allele(s) of the COMT gene at amino acid position 158 in a biological sample of the subject;   b) determining the proline level of the subject; and   c) modifying the course of treatment of the subject, if necessary, including administering a different proline modulator to the subject or stopping or omitting treatment with a proline modulator, based upon the presence or absence of a Val 158 Met polymorphism in the COMT gene.       

     The present invention also provides a diagnostic system for identifying a subject with a disorder who will benefit from treatment with an agent that increases or decreases proline levels comprising:
         determining the identity of the allele(s) of the Val 158 Met locus associated with the COMT gene using a biological sample from the subject;   wherein the presence of Val/Val at the locus is indicative of a subject who will benefit from an agent that increases proline levels and wherein the presence of at least one Met allele at the locus is indicative of a subject who will benefit from an agent that decreases proline levels.       

     The present invention also provides a method for treating or ameliorating the effects of a disorder in a subject in need thereof comprising:
         a) obtaining a biological sample from the subject;   b) determining, in the biological sample, the presence or absence of a Val 158 Met polymorphism in the COMT gene; and   c) administering to the subject, if appropriate based on the results of step (b), an effective amount of an agent that increases proline levels if the subject is determined from step (b) to have a Val/Val genotype at codon 158; or   d) administering to the subject, if appropriate based on the results of step (b), an effective amount of an agent that decreases proline levels if the subject is determined from step (b) to have a Val/Met or Met/Met genotype at codon 158.       

     The present invention also provides a method for treating or ameliorating the effects of a disorder in a subject in need thereof comprising:
         a) determining, using a biological sample of the subject, the presence or absence of a Val 158 Met polymorphism in the COMT gene of the subject; and   b) administering to the subject, if clinically appropriate, an effective amount of an agent that increases proline levels if the subject is determined from step (a) to have a Val/Val genotype at codon 158; or   c) administering to the subject, if clinically appropriate, an effective amount of an agent that decreases proline levels if the subject is determined from step (a) to have a Val/Met or Met/Met genotype at codon 158.       

     The present invention also provides a method for eradicating or reducing a negative symptom experienced by a subject who suffers from a disorder comprising:
         d) obtaining a biological sample from the subject;   e) determining, in the biological sample, the presence or absence of a Val 158 Met polymorphism in the COMT gene; and   f) administering to the subject, if clinically appropriate, an effective amount of an agent that increases proline levels if the subject is determined from step (b) to have a Val/Val genotype at codon 158; or   g) administering to the subject, if clinically appropriate, an effective amount of an agent that decreases proline levels if the subject is determined from step (b) to have at least one Met allele at codon 158; or   h) modifying the course of treatment of the subject, if clinically appropriate, including stopping or omitting treatment with a proline modulator, based upon the presence or absence of a Val 158 Met polymorphism in the COMT gene.       

    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. 
       The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. 
         FIG. 1  shows a boxplot of fasting plasma proline levels plotted for controls (174.28±55.97, n=90), bipolar disorder patients (168.75±45.50, n=40) and schizophrenia patients (215.84±63.00, n=64). Red jittered points represent individual data. The horizontal line within each box represents the group mean (mean±SD reported). The box indicates the interquartile range (IQR). The whiskers extend to the most extreme data point which is 1.5 times the IQR. While hyperprolinemia was present in 26.6% of schizophrenia (SZ) patients (17/64), the proportion of bipolar disorder (BPD) patients exhibiting peripheral hyperprolinemia (3/37; 7.5%) was not significantly different to controls (5/85; 5.6%) (Fisher&#39;s exact p=0.70). 
         FIG. 2A  shows a scatterplot graph of the relationship between proline and negative symptoms as measured using the Scale for the Assessment of Negative Symptoms (SANS), plotted for patients with the Met/Met (n=21, red diamonds), Val/Met (n=32, blue triangles) and Val/Val (n=42, green squares) COMT genotypes. Lines represent the predicted values from the regression model for each genotype, with 95% confidence intervals. There was a significant positive relationship between proline and SANS score in Met/Met and Val/Met patients, with high proline levels being associated with high SANS scores. Conversely there existed a significant negative relationship in Val/Val patients, with high proline associated with lower levels of negative symptoms. 
         FIG. 2B  shows scatterplot graphs of the relationship between proline and total negative symptoms, as assessed using the SANS, by COMT genotype (Met allele (left panel) or Val/Val (right panel)). There was a significant positive relationship between total SANS score and proline in schizophrenia patients with the Met allele (spearman&#39;s rho=0.36, p=0.009, n=53), while conversely there was a significant negative relationship between total SANS score and proline in Val/Val schizophrenia patients (spearman&#39;s rho=−0.47, p=0.0019, n=42). 
         FIG. 3  shows a boxplot illustrating that negative symptoms, as assessed by the total SANS score, were significantly lower in VPA treated patients with the COMT Val/Val genotype (mean=14.6±12.67, n=15, green), as compared to pooled Met/Met (mean=30.67±17.1, n=3, red) and Val/Met (mean=25.6±17.93, n=10, blue) genotypes (F(1,26)=4.63, p=0.0408). Subjects were included if they had received 48 hours or more of VPA treatment, within 48 hours of the study visit (n=28, three subjects were dropped because they had less than 48 hours of VPA treatment). Black jittered points represent individual data. The horizontal line within each box represents the group median. The box indicates the IQR. The whiskers extend to the most extreme data point which is 1.5 times the IQR. 
         FIG. 4  is a graph showing the relationship between proline and percent change in negative symptoms, plotted for patients with the COMT Met allele (n=27, purple diamonds) and Val/Val genotype (n=16, green triangles). Lines represent the predicted values from the regression model. As proline rose, Val/Val patients exhibited a greater negative percent change in symptoms, thus their symptoms decreased. Conversely, there existed a positive relationship between change in symptoms and proline in Met allele carriers: those with high proline had less of a decrease of negative symptoms. Negative symptoms were evaluated using the following items from the Brief Rating Psychiatric Scale (BPRS): item 3 (emotional withdrawal), 13 (motor retardation), 14 (uncooperativeness), 16 (blunted affect) and 18 (disorientation). Percent change in symptoms was calculated using the following formula: ((negative symptoms at visit 2−negative symptoms at visit 1)/negative symptoms at visit 1)×100%. 
         FIG. 5  is a graph showing the percent change in negative symptoms in bipolar disorder patients treated with VPA, by COMT genotype. Val/Val VPA treated bipolar patients had a greater overall percent reduction in negative symptoms (mean=−0.156±0.10, n=8) as compared to Met carrier patients (mean=−0.056±0.28, n=13). However, this result did not reach statistical significance (Mann-Whitney z=0.95, p=0.34), likely due to the variability observed in the Met patients as well as the small sample size. Black jittered points represent individual data. The horizontal line within each box represents the group median. The box indicates the IQR. The whiskers extend to the most extreme data point which is 1.5 times the IQR. The percent change in symptoms was calculated as: ((total negative symptoms subscale at visit 2−total negative subscale at visit 1)/(total negative subscale at visit 1))×100%. 
         FIG. 6  shows scatterplot graphs of the direct relationship between the change in proline level (pre- to post-medication) and the change in negative symptoms. The top panel shows ten bipolar disorder Met allele carriers (Met/Met or Val/Met) that had a strong positive relationship between the change in proline and the percent change in negative symptoms: as proline increased, a positive change was observed in negative symptoms, suggesting a worsening of symptoms over time, although this result did not reach significance (p=0.19), likely due to the small sample size. The bottom panel shows that Val/Val patients treated with valproate (n=8) had a negative relationship between the change in proline and symptoms (spearman&#39;s rho=−0.4), although this result again did not reach significance likely due to the small sample size (p=0.3). 
         FIG. 7  is a scatterplot graph showing the relationship between blood VPA level (in μg/ml) and percent change in negative symptoms. The left panel shows nine Met allele carriers, only two of whom showed improvement in negative symptoms after treatment onset. The right panel shows seven ValNal patients, five of whom improved after VPA treatment. The difference between genotypes did not reach significance (p=0.07), likely due to the small sample size. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     One embodiment of the present invention is a method for predicting the clinical response of a subject with a disorder to a proline modulator comprising:
         a) obtaining a biological sample from the subject;   b) determining the identity of the allele(s) of the Val 158 Met locus associated with the COMT gene in the sample;   wherein the presence of ValNal is indicative of a subject who will benefit from an agent that increases proline levels, and wherein the presence of at least one Met allele is indicative of a subject who will benefit from an agent that decreases proline levels; and   c) administering, if appropriate based on the results of step b), an effective amount of a proline modulator to the subject to achieve an appropriate clinical response.       

     As used herein, the term “disorder” broadly refers to a syndrome, condition, chronic illness or a particular disease. For example, the disorder may be a psychiatric disorder. In the present invention, a “psychiatric disorder” is one of a number of disorders that affect mood, thinking, and behavior. Thus, as used herein, “psychiatric disorder” includes but is not limited to: schizophrenia, bipolar disorder, schizoaffective disorders, schizophreniform disorders, schizotypal and schizoid personality disorders, delusional disorders, 22q11.2 deletion syndrome, mood disorders, anxiety disorders, substance use disorders, and personality disorders. 
     Other non-limiting examples of disorders according to the present invention include: schizophrenia, bipolar disorder, schizophrenia spectrum and other psychotic disorders, 22q11.2 deletion syndrome, depressive disorders, mood disorders, Alzheimer&#39;s disease, substance use disorders, addictive disorders, alcohol use disorder (AUD), anxiety disorders, obsessive-compulsive disorders, traumatic brain injury (TBI), and trauma and stressor-related disorders. In a preferred embodiment, the disorder is e.g., schizophrenia, bipolar disorder, alcohol use disorder (AUD) or traumatic brain injury (TBI). 
     As used herein, the terms “treat,” “treating,” “treatment” and grammatical variations thereof mean subjecting an individual subject to a protocol, regimen, process or remedy, in which it is desired to obtain a physiologic response or outcome in that subject, e.g., a patient. However, because every treated subject may not respond to a particular treatment protocol, regimen, process or remedy, treating does not require that the desired physiologic response or outcome be achieved in each and every subject or subject population, e.g., patient population. Accordingly, a given subject or subject population, e.g., patient population may fail to respond or respond inadequately to treatment. The term “clinical response” as used herein means a reduction of the severity or number of symptoms or characteristics of a disorder, during or following treatment. 
     In some aspects of this and other embodiments, the subject is a mammal. Preferably, the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals. More preferably, the mammal is a human. 
     As used herein, a “biological sample” means a biological specimen, which may be a bodily fluid or a tissue. Biological samples include, for example, whole blood, serum, plasma, cerebro-spinal fluid, leukocytes or leukocyte subtype cells (e.g. neutrophils, basophils, and eosinophils, lymphocytes, monocytes, macrophages), fibroblast sample, olfactory neuron sample, and tissues from the central nervous system, such as the cortex and hippocampus. Examples of preferred biological samples include, e.g., a blood sample, a biopsy sample, a plasma sample, a saliva sample, a tissue sample, a serum sample, a tear sample, a sweat sample, a skin sample, a cell sample, a hair sample, an excretion sample, a waste sample, a bodily fluid sample, a nail sample, a cheek swab, a cheek cell sample, or a mucous sample. 
     There is one single gene for COMT, which codes for both soluble COMT (S-COMT) and membrane-bound COMT (MB-COMT) using two separate promoters. The nucleic acid sequence for the human COMT gene is set forth in GenBank Accession Number Z26491 (see, e.g., SEQ ID NO: 1). Human S-COMT contains 221 amino acids (see, e.g., SEQ ID NO: 2), and the molecular mass is 24.4 kDa. Human MB-COMT (see, e.g., SEQ ID NO: 3) contains 50 additional amino acids, of which 20 are hydrophobic membrane anchors. The remainder of the MB-COMT molecule is suspended on the cytoplasmic side of the intracellular membranes. The corresponding molecular mass is 30.0 kDa. 
     A single nucleotide polymorphism (SNP) in the COMT gene causes a trimodal distribution of low, intermediate, and high activity. That polymorphism is caused by autosomal codominant alleles and leads to 3- to 4-fold differences in COMT activity. It has been shown that the molecular basis for this variation in activity is due to a transition of guanine to adenine at codon 158 of the COMT gene that results in a substitution of valine (Val) by methionine (Met) at position 158 in MB-COMT (SEQ ID NO: 3) or the corresponding amino acid 108 in S-COMT (SEQ ID NO: 2). The SNP polymorphism is referred to interchangeably herein as “rs4680” or “G158A” or “Val 158 Met”. In subjects with 22q11.2 deletion syndrome (22q11DS), there is only one allele which determines COMT activity. 
     Exemplary methods which may be used for the determination/identification of the COMT genotype or Val 158 Met polymorphism in the present invention are disclosed, for example, in US2003/0100476, which is incorporated herein by reference. Further examples of such methods include, but are not limited to, PCR-based restriction fragment length polymorphism analysis using the restriction enzyme αIII, allele specific hybridization, use of a primer in a polymerase chain reaction (PCR), such as, for example, anchor PCR or RACE PCR or in a ligase chain reaction (LCR), identification of alterations in restriction enzyme cleavage patterns, sequencing reactions, analysis of the protection from cleavage agents (such as, for example, nuclease, hydroxylamine or osmium tetroxide and with piperidine), recognition of mismatched base pairs in double strand DNA by specific enzymes, alterations in electrophoretic mobility, analysis of the movement of polymorphic fragments in polyacrylamide gels containing gradients of denaturant (denaturing gradient gel electrophoresis, DGGE), selective oligonucleotide hybridization (for example using a specialized exonuclease-resistance nucleotide), selective amplification depending on selective PCR or selective primer extension, oligonucleotide ligation assays, expansion methods using dideoxynucleotides derivatives, and Genetic Bit Analysis (GBA™). The detection of a variant in the COMT protein sequence can also be determined by methods such as in situ detection using an antibody specific to a variant sequence, immunoassays such as, for example, EIA or ELISA, immunofluorescence and the like. A preferred method for determining a COMT genotype is disclosed in Example 1. 
     As set forth above, the determination/identification of the COMT genotype or mutation in the COMT protein of a subject may be carried out by methods known to the skilled artisan. Such methods may be carried out, e.g., on a biological sample obtained from the subject, such as for example, a blood sample or a sample obtained after a biopsy has been carried out on the subject. Furthermore, any cell type or tissue may be utilized in the detection procedures described above. In a preferred embodiment, a bodily fluid, e.g., blood, is obtained from the subject to determine the presence of the allelic variant of a polymorphic region, such as the region including the Val 158 Met, in the COMT gene. A bodily fluid, e.g., blood, can be obtained by known techniques (e.g., venipuncture). Alternatively, nucleic acid tests can be performed on dry samples (e.g., skin). 
     As used herein, “an agent that increases or decreases proline levels” is used interchangeably with the phrase “proline modulator” and means any drug or other composition that increases or decreases the plasma proline levels in a subject. Such proline modulators may be administered to a subject in partly or fully deuterated forms, or containing other stable, medically appropriate isotopes such as, e.g.,  13 C. Non-limiting examples of agents that increase proline levels include valproic acid (VPA, 2-propylpentanoic acid), divalproex sodium, valproate (2-propylpentanoate), sodium valproate, magnesium valproate, lactic acid, miR-23b, miR-23a/b, (L or D)-proline, (L or D)-arginine, (L or D)-glutamine, (L or D)-ornithine, (L or D)-glutamic acid, (L or D)-glutamate, poly(L or D)-proline, poly(L or D)-glutamine, poly(L or D)-ornithine, poly(L or D)-glutamate, poly(L or D)-arginine, analogs of any of the foregoing, and combinations thereof, including mixed polypeptides of (L or D)-proline, (L or D)-glutamine, (L or D)-ornithine, (L or D)-arginine, (L or D)-glutamic acid, or (L or D)-glutamate. As used herein, an “analog” of an agent means a chemical compound that is structurally and functionally similar to the agent. In the present invention, combinations of such agents and/or their analogs is also contemplated. 
     Non-limiting examples of agents that decrease proline levels include, e.g., activators of PRODH or activators of peroxisomal proliferator-activated receptor gamma (PPARy). As used herein, “activators” when used with respect to PRODH or PPARy, means a drug or other composition that can increase the function or expression of PRODH or PPARy. In the present invention, a proline modulator that decreases proline levels in a subject includes, e.g., vitamin D 1 , vitamin D 2 , vitamin D 3 , vitamin D 4 , vitamin D 5 , Calcitriol, curcumin, one or more thiazolidinedione compounds, colchicine, Etanercept (Amgen/Pfizer), S26948 (Sigma-Aldrich), INT131 (InteKrin), phentoin, analogs of any of the foregoing, and combinations thereof. 
     In the present invention, a “proline modulator” also includes any molecule, enzyme, or treatment that affects circulating proline levels. For example, Table 51 (Supplemental Content), which is incorporated by reference herein in its entirety, identifies molecules that up- or down-regulate expression of genes regulating proline synthesis, transport, or metabolism. All such molecules are “proline modulators” of the present invention. The products of these genes influence circulating proline levels. These genes may also be targeted using known gene editing tools including, for example, CRISPR/Cas9 based systems, TALENs, etc., and thus are also considered “proline modulators” of the present invention. Table 1 contains a list of genes that are up- or down-regulated by valproate compounds, including VPA, valproate sodium salt and divalproate salt. These genes may provide targets for new treatments to modulate proline. 
     In the present invention, each embodiment optionally includes determining a proline level in the subject. Based on the determined proline level, if appropriate, the subject&#39;s treatment protocol may be adjusted. For example, by modifying the course of treatment, if necessary, including administering a different proline modulator to the subject, or stopping or omitting treatment with a proline modulator. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Genes regulated by VPA, valproate sodium salt or divalproate sodium salt 
               
               
                   
               
             
            
               
                 Up-regulated genes 
               
            
           
           
               
               
               
               
               
               
            
               
                 ABAT 
                 FOS 
                 EHHADH 
                 EGR1 
                 Acot1 
                 THRSP 
               
               
                 Cyp4a14 
                 DBP 
                 PDK4 
                 CA3 
                 TUBB2B 
                 CYP1A1 
               
               
                 NR1D2 
                 DPP8 
                 AKR1D1 
                 ANGPTL4 
                 ELOVL4 
                 AIG1 
               
               
                 KIF5C 
                 RETSAT 
                 ELOVL6 
                 FZD5 
                 PEX11A 
                 TIMP3 
               
               
                 CPT1A 
                 RRAGD 
                 CKB 
                 VNN1 
                 SPP1 
                 SAP30 
               
               
                 DLX5 
                 SLC22A8 
                 LYZ 
                 GCFC2 
                 MAPT 
                 HSD17B2 
               
               
                 ZFP37 
                 CLIC6 
                 FMO2 
                 PPAP2C 
                 CTSH 
                 CYP51A1 
               
               
                 SLC34A2 
                 CD36 
                 RGN 
                 TUBB2A 
                 H1F0 
                 GRPR 
               
               
                 CYP4A11 
                 UBR2 
                 AKR1C3 
                 Plscr2 
                 EGLN3 
                 NGFRAP1 
               
               
                 PFN2 
                 GPC3 
                 PENK 
                 USP2 
                 ARMCX2 
                 CEP104 
               
               
                 BCL6 
                 LRP11 
                 GABRB1 
                 IL1B 
                 TNRC18 
                 HLA-DQB1 
               
               
                 SERPINE1 
                 MT2A 
                 PGM2L1 
                 HMGCS1 
                 ATP8B3 
                 EDNRA 
               
               
                 GUCY1B3 
                 Prl2c2 
                 TNFRSF9 
                 FAM5C 
                 GJB5 
                 KRT23 
               
               
                 L1TD1 
                 RSPO4 
                 LOC284379 
                 S100A8 
                 PODXL 
                 Retnla 
               
               
                 AKR1C3 
                 FETUB 
                 CYP2S1 
                 UGT2B10 
                 BCMO1 
                 SERPINB2 
               
               
                 PRR15L 
                 DIO2 
                 CEACAM19 
                 GJB3 
                 GPX2 
                 PPBP 
               
               
                 SLC17A6 
                 GATA4 
                 MGARP 
                 FAM163A 
                 UPP1 
                 MMP10 
               
               
                 CD7 
                 EPGN 
                 ACPP 
                 LRRC2 
                 ATP13A4 
                 BST1 
               
               
                 TMPRSS11BNL 
                 GPR115 
                 WFDC12 
                 MUC5B 
                 HDC 
                 KRT8 
               
               
                 C4orf26 
                 GRIK2 
                 KRT18 
                 DPPA4 
                 QRFPR 
                 KCNA3 
               
               
                 LOC643037 
                 CRYAA 
                 FGB 
               
            
           
           
               
            
               
                 Down-regulated genes 
               
            
           
           
               
               
               
               
               
               
            
               
                 FAM111A 
                 CDK1 
                 ALAS2 
                 ARNTL 
                 TOLLIP 
                 CCNA2 
               
               
                 DCXR 
                 MX1 
                 SLC16A1 
                 C1orf210 
                 GPR37 
                 INMT 
               
               
                 IGFBP3 
                 IL6 
                 NPAS2 
                 MFAP4 
                 CDKN1A 
                 RRM2 
               
               
                 CHKA 
                 ENPP2 
                 LOC100912446 
                 FBXW5 
                 CCNB2 
                 IRF7 
               
               
                 CDH17 
                 RBM8A 
                 PC 
                 ADAMTSL3 
                 MFAP4 
                 ITGA11 
               
               
                 C1QTNF3 
                 ASPN 
                 DLK1 
                 PAPPA2 
                 CSPG4 
                 THBS4 
               
               
                 EGFL6 
                 COL8A1 
                 TSPAN18 
                 POSTN 
                 Tlr13 
                 LYZ 
               
               
                 FMOD 
                 SOX10 
                 AFF3 
                 ITGBL1 
                 TNMD 
                 NGFR 
               
               
                 AW551984 
                 ELN 
                 OGN 
                 PTGDS 
                 EPHA3 
                 NKD2 
               
               
                 COL14A1 
                 LPAR4 
                 PODN 
                 LDB2 
                 TRIM66 
                 FAM180A 
               
               
                 ADRA1B 
                 Ccl9 
                 HR 
                 MDGA1 
                 LPPR4 
                 SLC6A17 
               
               
                 PCSK9 
                 MSR1 
                 EDIL3 
                 SEMA3D 
                 LAMA2 
                 LCP1 
               
               
                 CTSS 
                 PTN 
                 EMR1 
                 CHRDL1 
                 RSPO2 
               
               
                   
               
            
           
         
       
     
     As used herein, an “analog” of vitamin D means a chemical compound that is structurally and functionally similar to vitamin D, or (1,25-dihydroxyvitamin D3 [1,25(OH) 2 D 3 ]). Non-limiting examples of vitamin D and analogs thereof include ergocalciferol, cholecalciferol, 22-oxacalcitriol, paricalcitol, doxercalciferol, alfacalcidol, dihydrotachystero, pharmaceutically acceptable salts thereof, and combinations thereof. 
     As used herein, an “analog” of curcumin means a chemical compound that is structurally and functionally similar to curcumin, and curcuminoid species. Non-limiting examples of curcumin and analogs thereof include curcumin, curcuma oil, turmerone, demethoxycurcum in, bisdemethoxycurcum in, pharmaceutically acceptable salts thereof, and combinations thereof. 
     Non-limiting examples of thiazolidinedione compounds include troglitazone, rosiglitazone, roglitazone, ciglitazone, darglitazone, englitazone, hydroxypioglitazone, ketopioglitazone, pioglitazone, pioglitazone hydrochloride, ragaglitazar, naveglitazar, aleglitazar, rivoglitazone, netoglitazone, pharmaceutically acceptable salts thereof, analogs of any of the foregoing, and combinations thereof. 
     Non-limiting examples of pharmaceutically acceptable salts include, for example, acid salts formed from inorganic or organic acids. Such acid salts are non-toxic and include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, and nitric acid; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, palmoic, maleic, hydroxymaleic, phenylacetic, glutamic, mesylate, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, and isethionic acid. Non-limiting examples of pharmaceutically acceptable base salts include, for example, aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, and zinc salts. 
     In some preferred embodiments, a pharmaceutically acceptable salt of valproate is sodium valproate. In other preferred embodiments, a pharmaceutically acceptable salt of valproate is magnesium valproate. 
     The terms “administering”, “administration” and variants thereof (particularly “administering” an agent or modulator) as used herein means introducing an agent, e.g., proline modulator into the body of a subject, such as a human, in need of such treatment. In the present invention, however, administration of such a proline modulator or agent is “appropriate” only if such administration will reduce, alleviate, or eradicate at least one negative symptom as defined herein. In the present invention, based on the result of the COMT genotype analysis and/or a subject&#39;s proline levels, it may be that no treatment should be administered, that a prior treatment with a proline modulator should be reduced or discontinued, or that a different proline modulator be administered. The appropriateness of a particular treatment option is readily determined by a medical professional based on the COMT genotype analysis and/or proline determination as disclosed herein. 
     In the present invention, an “effective amount” or a “therapeutically effective amount” of a proline modulator, an agent, a compound, or a composition disclosed herein is an amount of such material that is sufficient to effect beneficial or desired results as described herein when administered to a subject. Effective dosage forms, modes of administration, and dosage amounts may be determined empirically, and making such determinations is within the skill of the art. It is understood by those skilled in the art that the dosage amount will vary with the route of administration, the rate of excretion, the duration of the treatment, the identity of any other drugs being administered, the age, size, and species of mammal, e.g., human patient, and like factors well known in the arts of medicine and veterinary medicine. In general, a suitable dose of any active agent disclosed herein or a composition containing the same will be that amount of the active agent or composition, which is the lowest dose effective to produce the desired effect. 
     A suitable, non-limiting example of a dosage of a proline modulator according to the present invention may be from about 1 ng/kg to about 5000 mg/kg. In general, however, doses employed for adult human treatment typically may be in the range of 0.0001 mg/kg/day to 0.0010 mg/kg/day, 0.0010 mg/kg/day to 0.010 mg/kg/day, 0.010 mg/kg/day to 0.10 mg/kg/day, 0.10 mg/kg/day to 1.0 mg/kg/day, 1.00 mg/kg/day to about 200 mg/kg/day, 200 mg/kg/day to about 5000 mg/kg/day. For example, the dosage may be about 1 mg/kg/day to about 100 mg/kg/day, such as, e.g., 2-10 mg/kg/day, 10-50 mg/kg/day, or 50-100 mg/kg/day. The dosage of the proline modulator also may be about 1 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg, 50 mg/kg, 60 mg/kg, 70 mg/kg, 80 mg/kg, 90 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 175 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 400 mg/kg, 500 mg/kg, 600 mg/kg, 700 mg/kg, 800 mg/kg, 900 mg/kg, 1000 mg/kg, 1100 mg/kg, 1200 mg/kg, 1300 mg/kg, 1400 mg/kg, 1500 mg/kg, 1600 mg/kg, 1700 mg/kg, 1800 mg/kg, 1900 mg/kg, 2000 mg/kg, 2100 mg/kg, 2200 mg/kg, 2300 mg/kg, 2400 mg/kg, 2500 mg/kg, 2600 mg/kg, 2700 mg/kg, 2800 mg/kg, 2900 mg/kg, 3000 mg/kg, 3500 mg/kg, 4000 mg/kg, 5000 mg/kg. 
     With respect to proline modulators that are vitamin D and its analogs, the dosage of the proline modulator also may be denominated in International Units (IU) per day (IU/Day) and about 100 IU/day, 200 IU/day, 300 IU/day, 400 IU/day, 500 IU/day, 600 IU/day, 700 IU/day, 800 IU/day, 900 IU/day, 1000 IU/day, 1100 IU/day, 1200 IU/day, 1300 IU/day, 1400 IU/day, 1500 IU/day, 1600 IU/day, 1700 IU/day, 1800 IU/day, 1900 IU/day, 2000 IU/day, 2100 IU/day, 2200 IU/day, 2300 IU/day, 2400 IU/day, 2500 IU/day, 2600 IU/day, 2700 IU/day, 2800 IU/day, 2900 IU/day, 3000 IU/day, 3100 IU/day, 3200 IU/day, 3300 IU/day, 3400 IU/day, 3500 IU/day, 3600 IU/day, 3700 IU/day, 3800 IU/day, 3900 IU/day, 4000 IU/day, 4500 IU/day, 5000 IU/day, 5500 IU/day, 6000 IU/day, 6500 IU/day, 7000 IU/day, 7500 IU/day, 8000 IU/day, 9000 IU/day, 10,000 IU/day, 20,000 IU/day, 30,000 IU/day, 40,000 IU/day, 50,000 IU/day, 60,000 IU/day, 70,000 IU/day, 90,000 IU/day, 100,000 IU/day, 200,000 IU/day, 300,000 IU/day, 400,000 IU/day, 500,000 IU/day, 600,000 IU/day, 700,000 IU/day, 800,000 IU/day, 900,000 IU/day, 1,000,000 IU/day, 1,100,000 IU/day, 1,200,000 IU/day, 1,300,000 IU/day, 1,400,000 IU/day, or 1,500,000 IU/day. Preferably, the dosage of the vitamin D species and analogs range between about 1,000-1,500,000 IU administered on a periodic basis of dosing per day or per week or per month. 
     The effective dose of the proline modulator may be administered as two, three, four, five, six or more sub-doses, administered separately at appropriate intervals throughout the day. 
     The proline modulators, agents and compositions of the present invention may be administered in any desired and effective manner: for oral ingestion, or as an ointment or drop for local administration to the eyes, or for parenteral or other administration in any appropriate manner such as intraperitoneal, subcutaneous, topical, intradermal, inhalation, intrapulmonary, rectal, vaginal, sublingual, intramuscular, intravenous, intraarterial, intrathecal, or intralymphatic. Further, the proline modulators, agents and compositions of the present invention may be administered in conjunction with other treatments. Each proline modulator, agent and composition of the present invention may be encapsulated or otherwise protected against gastric or other secretions, if desired. 
     Another embodiment of the present invention is a method for monitoring the treatment of a subject in need thereof, the method comprising:
         a) obtaining a biological sample from the subject;   b) determining the genotype for the allele(s) of the COMT gene at amino acid position 158 in the biological sample;   c) determining the subject&#39;s proline level; and   d) modifying the course of treatment, if necessary, including administering a different proline modulator to the subject, or stopping or omitting treatment with a proline modulator, based upon the presence or absence of a Val 158 Met polymorphism in the COMT gene, and/or an increase or decrease in the subject&#39;s proline level.       

     Assays for determining a subject&#39;s genotype for the allele(s) of the COMT gene have been disclosed previously herein. Assays for determining a subject&#39;s proline level are well-known in the art. See, e.g., Wu, 1993; Inoue et al., 1996; Le Boucher et al., 1997; and Grainger et al., 2004; Liang et al., 2015. Non-limiting examples of proline assays include high throughput (HTP) proline assay, liquid chromatography/mass spectrometry (LC-MS/MS), and automated ion-exchange chromatography. In addition, commercial services for such assays are also available from vendors such as ARUP Laboratories (Salt Lake City, Utah). 
     As used herein, “modifying the course of treatment” refers to any change in the subject&#39;s treatment type and/or dosage, including administering a different proline modulator to the subject, stopping or omitting treatment with a proline modulator, adding an additional proline modulator to the treatment, and increasing or decreasing the dosage of a proline modulator. For subjects homozygous for Val, when it is determined that a subject&#39;s proline levels are not optimal, a target overnight fasting proline range after treatment onset of greater than about 158 μM is desired. Other target proline ranges of the invention include, for example, between 150 μM to 700 μM or 150 μM to 550 μM. For subjects with at least one Met allele, when it is determined that a subject&#39;s proline levels are not optimal, a target overnight fasting proline range after treatment onset below about 258 μM, such as below 170 μM, is desired. Other target proline ranges of the invention include, for example, between 80 μM to 318 μM. 
     Another embodiment of the present invention is a diagnostic system for identifying a subject with a disorder who will benefit from an agent that increases or decreases proline levels, comprising:
         a) obtaining a biological sample from the subject;   b) determining the identity of alleles of the Val 158 Met locus associated with the COMT gene in the sample;   wherein the presence of Val/Val is indicative of a subject who will benefit from an agent that increases proline levels and wherein the presence of at least one Met allele is indicative of a subject who will benefit from an agent that decreases proline levels.       

     In one aspect of the present invention, the diagnostic system may be used to assess prodromal subjects prior to onset of, e.g., psychotic symptoms, and to determine possible treatment protocols based on COMT and/or proline status. 
     One aspect of this embodiment may further comprise c) administering, to the subject who will benefit from an agent that increases proline levels, a composition that is selected from the group consisting of valproic acid (VPA), divalproex sodium, valproate, sodium valproate, magnesium valproate, lactic acid, miR-23b, miR-23a/b, (L or D)-proline, (L or D)-arginine, (L or D)-glutamine, (L or D)-ornithine, (L or D)-glutamic acid, (L or D)-glutamate, poly(L or D)-proline, poly(L or D)-glutamine, poly(L or D)-ornithine, poly(L or D)-glutamate, poly(L or D)-arginine, analogs of any of the foregoing, and combinations thereof, including mixed polypeptides of (L or D)-proline, (L or D)-glutamine, (L or D)-ornithine, (L or D)-arginine, (L or D)-glutamic acid, or (L or D)-glutamate. Alternatively, another aspect of this embodiment may further comprise c) administering, to the subject who will benefit from an agent that decreases proline levels, a composition that is selected from the group consisting of vitamin D 1 , vitamin D 2 , vitamin D 3 , vitamin D 4 , vitamin D 5 , Calcitriol, curcumin, one or more thiazolidinedione compounds, colchicine, Etanercept, S26948, INT131, phentoin, analogs of any of the foregoing, and combinations thereof. In this embodiment, the obtaining and determining steps are previously disclosed herein. 
     Another embodiment of the present invention is a kit comprising any of the diagnostic systems disclosed herein. Such kits are packaged together with instructions for its use. Such a kit may include, for example, one or more reagents for determination/identification of a COMT genotype or Val 158 Met polymorphism, a collection device, and one or more containers. The kit may be used in determining how to regulate proline levels in a subject to effect reduction or eradication of one or more negative symptoms of the subject. Exemplary reagents include, but are not limited to, primers, probes, antibodies, enzymes, oligonucleotides, and immunoassays. 
     Another embodiment of the present invention is a method for predicting the clinical response of a subject with a disorder to a proline modulator comprising:
         a) determining the identity of the allele(s) of the Val 158 Met locus associated with the COMT gene using a biological sample of the subject;   wherein the presence of Val/Val at the locus is indicative of a subject who will benefit from an agent that increases proline levels, and wherein the presence of at least one Met allele at the locus is indicative of a subject who will benefit from an agent that decreases proline levels; and   b) administering, if appropriate based on the results of step (a), an effective amount of a proline modulator to the subject to achieve a clinically appropriate response.
 
The determining and administering steps as well as the proline modulators of this embodiment are as previously disclosed herein.
       

     Another embodiment of the present invention is a method for monitoring the treatment of a subject with a disorder, the method comprising:
         a) determining the genotype for the allele(s) of the COMT gene at amino acid position 158 in a biological sample of the subject;   b) determining the proline level of the subject; and   c) modifying the course of treatment of the subject, if necessary, including administering a different proline modulator to the subject or stopping or omitting treatment with a proline modulator, based upon the presence or absence of a Val 158 Met polymorphism in the COMT gene.       

     Another embodiment of the present invention is a diagnostic system for identifying a subject with a disorder who will benefit from treatment with an agent that increases or decreases proline levels comprising:
         determining the identity of the allele(s) of the Val 158 Met locus associated with the COMT gene using a biological sample from the subject;   wherein the presence of Val/Val at the locus is indicative of a subject who will benefit from an agent that increases proline levels and wherein the presence of at least one Met allele at the locus is indicative of a subject who will benefit from an agent that decreases proline levels.
 
In the last two embodiments, the determining and modifying steps, if present, and the proline modulators, are as disclosed previously herein.
       

     Another embodiment of the present invention is a method for treating or ameliorating the effects of a disorder in a subject in need thereof. The method includes:
         a) obtaining a biological sample from the subject;   b) determining, in the biological sample, the presence or absence of a Val 158 Met polymorphism in the COMT gene; and   c) administering to the subject, if appropriate based on the results of step (b), an effective amount of an agent that increases proline levels if the subject is determined from step (b) to have a Val/Val genotype at codon 158; or   d) administering to the subject, if appropriate based on the results of step (b), an effective amount of an agent that decreases proline levels if the subject is determined from step (b) to have a Val/Met or Met/Met genotype at codon 158.       

     In this embodiment, the obtaining, determining, and administering steps have been disclosed previously herein. As used herein, the terms “ameliorate”, “ameliorating” and grammatical variations thereof mean to decrease the severity of the symptoms, particularly negative symptoms, of a disease in a subject, preferably a human. The polymorphism, disorders, biological samples, and agents for increasing or decreasing proline levels in this embodiment are as disclosed previously herein. 
     In one aspect of this embodiment, carrying out the method results in reducing or eradicating negative symptoms associated with the disorder. Examples of such negative symptoms include, but are not limited to, flat or blunted affect, social withdrawal, apathy, diminished emotional expression, avolition, alogia, autonomic dysfunction, impairment of executive performances, inattention, and behavioral problems. Preferred examples of negative symptoms according to the present invention include diminished emotional expression, avolition, impaired social functioning, alogia, apathy, anhedonia, or combinations thereof. 
     In another aspect of this embodiment, numerous ways to assess negative symptoms in a subject are provided, including, e.g., a Scale for Negative Symptoms (SANS) score, a Brief Psychiatric Rating Scale (BPRS) negative symptom sub-scale score, a Positive and Negative Syndrome Scale (PANSS) negative symptom sub-scale score, a Brief Negative Symptom Scale (BNSS) score, clinical assessment interview for negative symptoms, negative assessment, or other measures of negative symptoms in the subject. Other methods for detecting negative symptoms known in the art may also be used. Such additional methods include, e.g., tests and assessments for physical, physiological, or behavioral markers, including neuroimaging, electroencephalogram (EEG), and neurophysiological tests such as mismatched negativity (MMN), P3a, P50, and P100 indices, pre-pulse inhibition (PPI), startle habituation, and antisaccade. In the present invention, however, the preferred method for assessing negative symptoms is the SANS score as disclosed in more detail in the Examples and Figures. 
     Another embodiment of the present invention is a method for treating or ameliorating the effects of a disorder in a subject in need thereof comprising:
         a) determining, using a biological sample of the subject, the presence or absence of a Val 158 Met polymorphism in the COMT gene of the subject;       

     and
         b) administering to the subject, if clinically appropriate, an effective amount of an agent that increases proline levels if the subject is determined from step a) to have a Val/Val genotype at codon 158; or   c) administering to the subject, if clinically appropriate, an effective amount of an agent that decreases proline levels if the subject is determined from step a) to have a Val/Met or Met/Met genotype at codon 158.
 
In this embodiment, the determining and administering steps, and the agents, are as disclosed previously herein.
       

     Yet another embodiment of the present invention is a method for eradicating or reducing a negative symptom experienced by a subject who suffers from a disorder comprising:
         a) obtaining a biological sample from the subject;   b) determining, in the biological sample, the presence or absence of a Val 158 Met polymorphism in the COMT gene; and   c) administering to the subject, if clinically appropriate, an effective amount of an agent that increases proline levels if the subject is determined from step b) to have a Val/Val genotype at codon 158; or   d) administering to the subject, if clinically appropriate, an effective amount of an agent that decreases proline levels if the subject is determined from step b) to have at least one Met allele at codon 158.       

     In this embodiment, the negative symptoms are as described previously. Furthermore, the obtaining, determining, and, if appropriate, administering steps in this embodiment have been described previously. 
     Below are a set of genes and variants which (individually and/or in various combinations and/or groups) may modify interaction(s) of proline and/or (glutamate, GABA, glycine, L- and/or D-serine, D-cycloserine, and molecules listed above) with COMT. They include proline and dopamine metabolism and transporter genes. 
     COMT genotypes and/or gene-associated variants including the Val 158 Met polymorphism and/or rs6270 and/or rs6269 and/or rs4633 and/or rs4818 and/or rs6267 and/or rs5031015 and/or rs4986871 and/or rs4680 (including either allele and/or sequence alternative for COMT Uniprot variant Ids: VAR_013925 and/or VAR_013926 and/or VAR_020274 and/or VAR_020275 and/or VAR_005139 (both alleles (Val and/or Met)) and/or VSP_018778. 
     PRODH variants including the rs450046 and/or rs372055 and/or rs2904552 and/or rs137852934 and/or rs4819756 and/or rs193919334 and/or rs2008720 and/or rs2904551 and/or rs3970559 and/or rs1807467 and/or rs2870983 and/or rs3970555 and/or rs2238731 and/or rs2870984 and/or (including either allele alternative for PRODH Uniprot Variant ids: VAR_029566 and/or VAR_029568 and/or VAR_029569 and/or VAR_029570 and/or VAR_029571 and/or VAR_029572 and/or VAR_029573 and/or VAR_029575 and/or VAR_029577 and/or VAR_029567 and/or VAR_029569 and/or VAR_029571 and/or VAR_029574 and/or VAR_029575 and/or VAR_029577. 
     SLC6A7 variants and associated variants including rs1468564, and/or rs13153971 and/or rs3776083. 
     SLC6A20 variants and associated variants including rs17279437 and/or rs2271615 and/or rs6770261 and/or rs758386 and/or rs4327428. 
     SLC6A15 variants and associated variants including rs1545843 and/or rs12424429 and/or rs3782369 and/or rs1031681. 
     SLC6A18 variants and associated variants including rs34469326 and/or rs7728667 and/or rs7705355 and/or rs113861454 and/or rs4073918 and/or rs147278493 and/or rs12522796 and/or rs4975623 and/or rs4975625 and/or rs7447815 and/or rs7728646. 
     PEPD variants and associated variants including rs121917721 and/or rs121917724 and/or rs121917723 and/or rs17570 and/or rs121917722 and/or rs121917725 and/or rs267606944 and/or rs267606943 and/or rs757386104 and/or rs797045185 and/or rs794728007 and/or rs747700126 and/or rs794728008 and/or rs3786897 and/or rs4805885 and/or rs731839 and/or rs8182584 and/or rs889140 and/or (including either allele alternative for Prolidase PEPD Uniprot Variant ids:VAR_011614 and/or VAR_004404 and/or VAR_011615 and/or VAR_004405 and/or VAR_004406). 
     MAOA variants and associated variants including rs77698881 and/or rs587777457 and/or rs1799835 and/or rs1800466 and/or rs1137070 and/or rs1465107 and/or rs2072743 and/or rs2235186 and/or rs2283725 and/or rs3027400 and/or rs3027407 and/or rs3027409 and/or rs5906883 and/or rs5906957 and/or rs5953210 and/or rs6323 and/or rs6609257 and/or rs72554632 and/or rs796065311 and/or rs796065312 and/or rs909525 and/or rs979606 and/or (including either allele and/or sequence alternative for MAOA Uniprot Variant and associated variant ids VAR_036545 and/or id VSP_045173). 
     MAOB variants and associated variants including rs10521432 and/or rs1799836 and/or rs2283729 and/or rs3027415 and/or rs6651806 and/or (including either allele and/or sequence alternative for MAOB Uniprot Variant and associated variant ids VSP_057047 and/or VSP_057048 and/or VSP_057049). 
     GAD1 variants and associated variants including rs121918345 and/or rs45566933 and/or rs769403 and/or rs769402 and/or rs1049736 and/or rs11542313 and/or rs12185692 and/or rs2058725 and/or rs2241165 and/or rs3749034 and/or rs3762555 and/or rs3791850 and/or rs3791851 and/or rs3791878 and/or rs3828275 and/or rs769390 and/or rs769391 and/or rs769404 and/or rs769407. 
     GAD2 variants and associated variants including rs8190591 and/or rs8190600 and/or rs2839672 and/or rs2839673 and/or rs8190671 and/or rs2839678 and/or rs8190730 and/or rs1805398 and/or rs185649317 and/or rs2236418 and/or rs8190590 and/or rs8190748 and/or rs992990. 
     Additional Definitions 
     The term “amino acid” means naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function similarly to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, gamma-carboxyglutamate, and O-phosphoserine. An “amino acid analog” means compounds that have the same basic chemical structure as a naturally occurring amino acid, e.g., a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs may have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Imino acids such as, e.g., proline, are also within the scope of “amino acid” as used here. An “amino acid mimetic” means a chemical compound that has a structure that is different from the general chemical structure of an amino acid, but that functions similarly to a naturally occurring amino acid. 
     As used herein, the terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers, those containing modified residues, and non-naturally occurring amino acid polymers. 
     “Nucleic acid” or “oligonucleotide” or “polynucleotide” used herein mean at least two nucleotides covalently linked together. Many variants of a nucleic acid may be used for the same purpose as a given nucleic acid. Thus, a nucleic acid also encompasses substantially identical nucleic acids and complements thereof. 
     Nucleic acids may be single stranded or double stranded, or may contain portions of both double stranded and single stranded sequences. The nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine and isoguanine. Nucleic acids may be synthesized as a single stranded molecule or expressed in a cell (in vitro or in vivo) using a synthetic gene. Nucleic acids may be obtained by chemical synthesis methods or by recombinant methods. 
     The nucleic acid may also be a RNA such as a mRNA, tRNA, short hairpin RNA (shRNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), transcriptional gene silencing RNA (ptgsRNA), Piwi-interacting RNA, pri-miRNA, pre-miRNA, micro-RNA (miRNA), or anti-miRNA, as described, e.g., in U.S. patent application Ser. Nos. 11/429,720, 11/384,049, 11/418,870, and 11/429,720 and Published International Application Nos. WO 2005/116250 and WO 2006/126040. 
     The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. 
     For recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the numbers 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated. 
     EXAMPLES 
     The following examples are provided to further illustrate certain aspects of the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way. 
     Example 1 
     Materials and Methods 
     Participants: 
     Male and female, African American, Caucasian and Hispanic patients, aged 18-65, were recruited from Bellevue Hospital Center (BHC). A diagnosis of schizophrenia or bipolar disorder was confirmed using the Structured Clinical Interview for DSM IV Disorders (SCID). After description of the study to subjects, written informed consent was obtained in accordance with IRB regulations. 
     For schizophrenia inpatients, recruitment was cross-sectional and independent of their duration of hospitalization. Psychiatric symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Brief Psychiatric Rating Scale (BPRS). Proline levels of a subset of the schizophrenia patients, those who did not receive treatment with VPA or divalproex, were reported previously (Clelland et al., 2011). 
     Bipolar patients were recruited upon presentation at the BHC Comprehensive Emergency Psychiatric Program. Psychiatric symptoms in bipolar disorder patients were measured at an admission visit (visit 1), using the BPRS. At a follow-up inpatient ward visit (visit 2), fasting bloods were collected plus a repeat BPRS assessment performed. Additionally, as shown in  FIG. 1 , an association with elevated proline in bipolar disorder patients was tested. It was found that patients did not have fasting proline levels different to controls, consistent with previous findings (Jacquet et al., 2005). 
     Determination of Fasting Plasma Levels: 
     Fasting morning blood draws were performed and proline measured in μmoles/liter as reported (Clelland et al., 2011). 
     Genotyping: 
     DNA was extracted from blood using the Puregene Blood Core Kit (Qiagen Inc) and the COMT fragment containing the Val 158 Met polymorphism amplified using the 5′-3′ primers: ACTGTGGCTACTCAGCTGTG (SEQ ID No: 4) and CCTTTTTCCAGGTCTGACAA (SEQ ID NO: 5). A step-down PCR was employed with an initial denaturation of 94° C.:15 minutes, then 12 cycles of 94° C.:30 seconds, 58° C.:45 seconds and 72° C.:30 seconds, followed by 31 cycles of 94° C.:30 seconds, 50° C.:45 seconds and 72° C.:30 seconds, with a final 72° C.:7 minute extension. Restriction enzyme N1aIII recognizes and cleaves the amplicon into Val (114 bp) or Met (96 bp) fragments, visualized following electrophoreses. To confirm genotyping accuracy, 25% of samples were repeat assayed. 
     Statistical Analysis: 
     Group differences were assessed using ANOVA, Kruskal-Wallis and Mann-Whitney tests (following skewness and kurtosis normality tests), χ 2  or Fisher exact tests. Means±standard deviations (SD) were reported, plus Bonferroni adjusted p-values where appropriate. Genotype distributions were tested for Hardy-Weinberg equilibrium (HWE) using a χ 2  or exact test. 
     Linear regression was employed to test for an interaction between fasting plasma proline and COMT on symptoms in schizophrenia, modelling the relationships of these variables on outcomes of total SANS, SAPS and BPRS scores. Based upon the schizophrenia sample result, the primary outcome for bipolar patients was assessed using the BPRS negative symptom subscale (Kane et al., 1988), and percent reduction in negative symptoms calculated. Positive symptom subscale of the BPRS (Id.) and total BPRS scores were also investigated. When outliers in the data or leverage points were identified, a robust regression procedure was employed using an MM estimator to minimize data-point effects (SASv9.3). 
     Significant models were investigated further: To assess utility in adjusting the dependent variable, demographic and clinical covariates were entered into a bivariate regression and terms found to have p-values of &lt;0.10 carried forward to a multivariate model. Gender was a covariate in all models, to adjust for previously reported proline gender differences (Jacquet et al., 2005; Tomiya et al., 2007; Clelland et al., 2011). Model fit and selection was determined using the Wald test, testing the null hypothesis that non-significant (p&gt;0.05) covariate parameters were simultaneously equal to zero in full and subsequent reduced models. Statistical analysis was performed in SASv9.3, Stata ICv12, with graphs plotted in GGplot2v1.0.1 in Rv3.1.2. 
     Example 2 
     Results 
     COMT Genotype Modifies the Relationship Between Proline and Negative Symptoms of Schizophrenia: 
     The schizophrenia sample consisted of 95 patients. Although recruitment was not targeted by COMT genotype, patients were well matched on demographic characteristics and medication use across genotypes (Table 2). 
     In the entire sample, fasting plasma proline was not significantly different across genotypes (range 87 μM to 502 μM). There were also no differences in BPRS total or negative symptoms (SANS total score), however positive symptoms were significantly different: Met/Met patients had lower SAPS scores than Val/Met (Mann-Whitney z=2.52, adjusted p=0.035) or Val/Val patients (z=2.92, adjusted p=0.001), as previously reported (Goghari &amp; Sponheim, 2008). 100% accuracy was achieved from confirmatory re-genotyping and a sample of 90 control subjects were in HWE for COMT Val 158 Met (p&gt;0.05, data not shown). However, COMT distributions of the schizophrenia patients deviated from HWE (χ 2 =8.08, df=1, p&lt;0.05). Although deviations for this polymorphism in schizophrenia have been reported (Joober et al., 2002), this finding may represent substructure due to mixed ethnicity: when stratified by ethnicity, all groups were in HWE (p&gt;0.05). 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Demographic and Clinical Characteristics of Schizophrenic Patients (SZ), n = 95 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Met/Met 
                 Val/Met 
                 Val/Val 
                   
               
               
                   
                 n = 21 
                 n = 32 
                 n = 42 
                 Prob a   
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                 Characteristic 
                   
                   
                   
                   
               
               
                 Gender, n (row %) 
                   
                   
                   
                 0.288 
               
               
                 Female 
                 11 (23.4) 
                 19 (40.4) 
                 17 (36.2) 
               
               
                 Males 
                 10 (20.8) 
                 13 (27.1) 
                 25 (52.1) 
               
               
                 Ethnicity, n (row %) 
                   
                   
                   
                 0.096 
               
               
                 African American 
                  5 (13.5) 
                 10 (27.0) 
                 22 (59.5) 
               
               
                 Caucasian 
                 10 (35.7) 
                 10 (35.7) 
                  8 (28.6) 
               
               
                 Hispanic 
                  6 (20.0) 
                 12 (40.0) 
                 12 (40.0) 
               
               
                 Age (years), mean ± SD 
                 40.9 ± 10.9 
                 39.1 ± 11.5 
                 39.9 ± 11.6 
                 0.820 
               
               
                 Smoking Status b , n (row %) 
                   
                   
                   
                 0.389 
               
               
                 Current or Previous 
                 15 (24.6) 
                 24 (39.3) 
                 22 (36.1) 
               
               
                 Never Smoked 
                  6 (20.7) 
                  8 (27.6) 
                 15 (51.7) 
               
               
                 History of Alcoholism, n (%) 
                   
                   
                   
                 0.426 
               
               
                 Neither 
                 17 (23.6) 
                 27 (37.5) 
                 28 (38.9) 
               
               
                 Abuse 
                  1 (10.0) 
                  2 (20.0) 
                  7 (70.0) 
               
               
                 Dependence 
                  3 (23.1) 
                  3 (23.1) 
                  7 (53.8) 
               
               
                 Education c   
                 3.6 ± 1.9 
                 3.1 ± 1.0 
                 3.4 ± 1.5 
                 0.859 
               
               
                 Age at First Hospitalization d , mean ± 
                 23.5 ± 8.0  
                  25 ± 6.5 
                 23.7 ± 7.5  
                 0.465 
               
               
                 SD 
               
               
                 Hospital Duration (days) e , mean ± SD 
                 19.1 ± 17.1 
                 21.9 ± 23.4 
                 20.0 ± 19.6 
                 0.998 
               
               
                 Fasting Plasma Proline, umol/L 
                 219.9 ± 91.6  
                 240.5 ± 68.6  
                 246.4 ± 91.1  
                 0.391 
               
               
                 Symptoms 
               
               
                 BPRS f  Total Symptoms, mean ± SD 
                  32 ± 8.5 
                 33.6 ± 7.1  
                 33.6 ± 8.4  
                 0.500 
               
               
                 SAPS g  Total Symptoms, mean ± SD 
                 10.3 ± 8.3  
                 15.8 ± 9.6  
                 18.2 ± 10.1 
                 0.006* 
               
               
                 SANS h  Total Symptoms, mean ± SD 
                   24 ± 16.8 
                 21.8 ± 13.1 
                 17.5 ± 13.9 
                 0.127 
               
               
                 Neuroleptic Medications 
               
               
                 Neuroleptic Type, n (row %) 
                   
                   
                   
                 0.348 
               
               
                 Typical only 
                  5 (27.8) 
                  3 (16.7) 
                 10 (55.6) 
               
               
                 Atypical only 
                 13 (22.4) 
                 19 (32.8) 
                 26 (44.8) 
               
               
                 Both 
                  3 (16.7) 
                  9 (50.0) 
                  6 (33.3) 
               
               
                 None 
                 0 
                  1 (100) 
                 0 
               
               
                 Daily CPZE dose i , mean ± SD 
                 490.6 ± 234.0 
                 571.1 ± 418.1 
                 526.8 ± 281.0 
                 0.981 
               
               
                 Mood Stabilizing Medications 
               
               
                 Total Number Administered, n (row 
                   
                   
                   
                 0.786 
               
               
                 %) 
               
               
                 0 
                 15 (26.3) 
                 19 (33.3) 
                 23 (40.4) 
               
               
                 1 
                  6 (16.7) 
                 12 (33.3) 
                 18 (50.0) 
               
               
                 2 
                 0 
                 1 (50)  
                 1 (50)  
               
               
                 VPA Treatment, n (row %) 
                   
                   
                   
                 0.327 
               
               
                 Yes 
                  4 (12.9) 
                 11 (35.5) 
                 16 (51.6) 
               
               
                 No 
                 17 (26.6) 
                 21 (32.8) 
                 26 (40.6) 
               
               
                 Other Medications 
               
               
                 Benzodiazapines, yes: n (row %) 
                  4 (21.0) 
                  8 (42.1) 
                  7 (36.8) 
                 0.641 
               
               
                 Antidepressants, yes: n (row %) 
                 1 (9.1) 
                  5 (45.4) 
                  5 (45.4) 
                 0.596 
               
               
                   
               
               
                   a *= significant p-value when comparing characteristic across three COMT genotypes, calculated by one-way ANOVA, Kruskal-Wallis, or Fisher exact tests. 
               
               
                   b n = 90, five subjects not reported. 
               
               
                   c Recorded as a continuous variable from the SCID (range 2-8). n = 93, two subjects not reported. 
               
               
                   d n = 60 for whom this characteristic could be obtained. 
               
               
                   e Days in hospital prior to fasting blood draw. 
               
               
                   f Brief Psychiatric Rating Scale. 
               
               
                   g Schedule for Assessment of Positive Symptoms. 
               
               
                   h Schedule for Assessment of Negative Symptoms. 
               
               
                   i Chlorpromazine (CPZ) equivalent dose, n = 94 as one subject&#39;s NL had no CPZ equivalent. 
               
            
           
         
       
     
     Testing the primary hypothesis of effect modification, a significant interaction was observed between COMT genotype and proline on negative symptoms in schizophrenia patients (n=95, interaction β coefficient=0.082, p&lt;0.0001). As shown in  FIGS. 2A and 2B , for patients with both the Met/Met or Val/Met genotypes, high proline was associated with high SANS scores, while conversely high proline in Val/Val patients was associated with lower levels of negative symptoms. Stratifying by COMT (Met allele carrier or Val/Val), for Met carriers, every 100 μM increase in proline (approximately 1SD from the mean proline level) was associated with a SANS total score increase of over 8 points (β coefficient=0.084, p=0.001). Conversely, for Val/Val patients, every 100 μM increase in proline decreased SANS total scores by nearly 7 points (β=−0.067, p=0.003). Thus at proline levels only approximately 1 SD above the group means, Met carriers with a fasting plasma proline of 332 μM had a predicated SANS score of 30, while Val/Val patients with proline of 346 μM had a predicted score of only 10. 
     Possible confounds on this relationship were assessed (see Table 3). While there was no relationship between SANS score and either medication type, neuroleptic dose (summarized as daily chlorpromazine equivalents), or the number of days in hospital prior to blood draw and symptom assessment, covariate analysis showed that ethnicity and alcohol use were predictors of SANS score (p&lt;0.1, Table 3), and along with gender were taken forward to a multivariate model (Table 4). Model fit was determined with the final model retaining genotype, proline, alcohol use, and the highly significant COMT-proline interaction (p&lt;0.0001). The significant interaction also remained in a stratified analysis following removal of patients reporting alcohol abuse/dependence (p&lt;0.001, n=72). Interestingly, there was no interaction of COMT genotype on the relationship between fasting peripheral proline and positive symptoms (interaction β=−0.005, p=0.64), or total symptoms (interaction β=−0.23, p=0.097), suggesting specificity of the relationship to negative symptoms. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Bivariate Association Between Schizophrenia Patient 
               
               
                 Demographic and Clinical Characteristics, with 
               
               
                 Total SANS Score, n = 95 
               
            
           
           
               
               
               
            
               
                 Characteristic 
                 β (95% Cl) 
                 Prob 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Gender a   
                 −1.697 (−7.609, 4.215) 
                 0.570 
               
               
                 Ethnicity b   
               
               
                 African American v Caucasian 
                  6.059 (−1.026, 13.143) 
                 0.093* 
               
               
                 African American v Hispanic 
                  7.028 (0.079, 13.977) 
                 0.047* 
               
               
                 Age 
                  0.024 (−0.239, 0.287) 
                 0.857 
               
               
                 Education c   
                  0.389 (−1.660, 2.438) 
                 0.707 
               
               
                 Alcohol Dependence/abuse b   
               
               
                 None v Abuse 
                 −0.236 (−9.775, 9.303) 
                 0.961 
               
               
                 None v Dependence 
                 −9.505 (−18.023, −0.987) 
                 0.029* 
               
               
                 Smoking Status d   
                 −0.882 (−4.112, 2.349) 
                 0.589 
               
               
                 Hospital Duration e   
                  0.026 (−0.121, 0.172) 
                 0.729 
               
               
                 Daily CPZE dose f   
                  0.004 (−0.005, 0.014) 
                 0.353 
               
               
                 Neuroleptic (NL) Type b,g   
               
               
                 Atypical v Typical 
                  2.082 (−5.763, 9.930) 
                 0.599 
               
               
                 Atypical v both 
                 −1.584 (−9.430, 6.261) 
                 0.689 
               
               
                 Total Number of NLs 
                 −2.961 (−10.614, 4.692) 
                 0.444 
               
               
                 Administered h   
               
               
                 Total Number of Mood Stabilizers 
                  1.320 (−4.886, 7.526) 
                 0.674 
               
               
                 Administered i   
               
               
                 VPA Treatment j   
                 −0.578 (−7.157, 6.001) 
                 0.862 
               
               
                 Benzodiazapines 
                 −3.342 (−10.713, 4.028) 
                 0.370 
               
               
                   
               
               
                   a Binary variable: Male v female. 
               
               
                   b For categorical analysis the reference category is the first level listed for each variable. 
               
               
                   c Recorded as a continuous variable from the SCID (range 2-8) 
               
               
                   d Binary variable: Never v current or previous smokers, n = 90 as four subjects did not report smoking status. 
               
               
                   e Days in hospital prior to fasting blood draw and symptoms assessment. 
               
               
                   f Chlorpromazine (CPZ) equivalent dose, n = 93 as one subject&#39;s NL had no CPZ equivalent, and one subjects did not receive a NL. 
               
               
                   g n = 94, as one subject did not receive a NL. 
               
               
                   h Binary variable: one v two, n = 92 (as one subject did not receive a NL, and only two subjects were administered &gt;2 different NLs). 
               
               
                   i Binary variable: no versus yes, n = 92 (as three subjects had not received &lt;48 hours of VPA treatment). 
               
               
                   j Binary variable: none versus one, n = 93 (as only two subjects were administered &gt;1 mood stabilizers). 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Prediction of Negative Symptoms from Proline Level and COMT in Psychiatric Patients 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                 Test 
                   
                   
               
               
                   
                 β Coefficient 
                 SE 
                 statistic a   
                 Prob 
                 Wald test 
               
               
                   
                   
               
            
           
           
               
            
               
                 Schizophrenia Models (DV = Total SANS Score, n = 95) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Full Model b   
                   
                   
                   
                   
                   
               
               
                 Proline 
                 −0.1050 
                 0.0333 
                 9.94 
                 0.0016* 
               
               
                 COMT (ValVal, ValMet, MetMet) 
                 −13.0179 
                 4.2452 
                 9.40 
                 0.0022* 
               
               
                 Interaction (Proline = COMT) 
                 0.0744 
                 0.0169 
                 19.48 
                 &lt;.0001* 
               
               
                 Alcohol Use 
               
               
                 Alcohol Abuse v None 
                 −4.2178 
                 4.2706 
                 0.98 
                 0.3233 
               
               
                 Alcohol Dependence v None 
                 −9.0807 
                 3.5632 
                 6.49 
                 0.0108* 
               
               
                 Gender 
                 −1.0466 
                 2.3795 
                 0.19 
                 0.6600 
               
               
                 Ethnicity 
               
               
                 African-American v Caucasian 
                 3.0258 
                 3.0258 
                 1.14 
                 0.2866 
               
               
                 African-American v Hispanic 
                 4.6703 
                 2.8214 
                 2.74 
                 0.0979 
                 p = 0.517 c   
               
               
                 Final Model b   
               
               
                 Proline 
                 −0.0804 
                 0.0321 
                 6.28 
                 0.0122* 
               
               
                 COMT (ValVal, ValMet, MetMet) 
                 −9.6576 
                 4.0300 
                 5.74 
                 0.0166* 
               
               
                 Interaction (Proline × COMT) 
                 0.0651 
                 0.0161 
                 16.39 
                 &lt;.0001* 
               
               
                 Alcohol Use 
               
               
                 Alcohol Abuse v None 
                 −5.1234 
                 3.9854 
                 1.65 
                 0.1986 
               
               
                 Alcohol Dependence v None 
                 −9.7478 
                 3.3526 
                 8.45 
                 0.0036* 
                 p = 0.020 d   
               
            
           
           
               
            
               
                 Bipolar Disorder Models (DV = % Change in BPRS Negative Symptoms Scale, n = 43) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Full Model 
                   
                   
                   
                   
                   
               
               
                 Proline 
                 0.0012 
                 0.0006 
                 2.09 
                 0.044* 
               
               
                 COMT (Met/Met v ValVal) 
                 0.4281 
                 0.1650 
                 2.60 
                 0.014* 
               
               
                 Interaction (Proline × COMT) 
                 −0.0017 
                 0.0007 
                 −2.42 
                 0.022* 
               
               
                 Gender 
                 0.1960 
                 0.0656 
                 2.99 
                 0.005* 
               
               
                 Ethnicity 
               
               
                 African-American v Caucasian 
                 0.0186 
                 0.0839 
                 0.22 
                 0.826 
               
               
                 African-American v Hispanic 
                 −0.1528 
                 0.1052 
                 −1.45 
                 0.156 
               
               
                 Duration (days) between 
               
               
                 Assessments 
                 0.0049 
                 0.0070 
                 0.69 
                 0.492 
               
               
                 Neuroleptic Type 
               
               
                 Atypical Neuroleptic v None 
                 −0.0802 
                 0.0818 
                 −0.98 
                 0.334 
               
               
                 Typical Neuroleptic v None 
                 −0.1401 
                 0.2087 
                 −0.67 
                 0.507 
               
               
                 Both v None 
                 −0.1531 
                 0.1184 
                 −1.29 
                 0.206 
               
               
                 Benzodiazepines 
                 −0.0840 
                 0.0714 
                 −1.18 
                 0.249 
                 p = 0.056 e   
               
               
                 Final Model 
               
               
                 Proline 
                 0.0016 
                 0.0006 
                 2.55 
                 0.015* 
               
               
                 COMT (Met/Met v ValVal) 
                 0.5029 
                 0.1766 
                 2.85 
                 0.007* 
               
               
                 Interaction (Proline × COMT) 
                 −0.0021 
                 0.0007 
                 −2.83 
                 0.007* 
               
               
                 Gender 
                 0.1856 
                 0.0656 
                 2.83 
                 0.007* 
                 p = 0.0074 f   
               
               
                   
               
               
                   a χ 2  (Schizophrenia models using Robust linear regression) or t (Bipolar models using linear regression) 
               
               
                   b Robust regression, MM Estimation Method (28). 
               
               
                   c Robust Wald tests canonical linear hypothesis that combined effect of non-significant covariates (Gender and Ethnicity) is zero. 
               
               
                   d Robust Wald tests hypothesis that covariate effect (Alcohol use) is zero. 
               
               
                   e Wald tests canonical linear hypothesis that combined effect of non-significant covariates (Ethnicity, Duration, Neuroleptic Type and use of Benzodiazepines) is zero. 
               
               
                   f Wald tests hypothesis that covariate effect (Gender) is zero. 
               
            
           
         
       
     
     Example 3 
     Valproate Treated COMT ValNal Schizophrenia Patients have Significantly Lower Negative Symptoms than Met Allele Carriers: 
     An effect of VPA on plasma proline has been reported (Jacquet et al., 2005) and VPA-treated schizophrenia patients in the current study had significantly higher proline (mean=299.29±94.76, n=28) than those who did not receive VPA (mean=215.84±63, n=64) (z=−3.97, p=0.0001). Considering the finding of an interaction between COMT and proline on negative symptoms, the hypothesis was that VPA treated Val/Val patients would respond differently to the concomitant high levels of proline, with respect to their negative symptoms, as compared to Met carriers. As shown in  FIG. 3 , VPA-treated Val/Val schizophrenia patients had significantly lower SANS total scores, averaging twelve points lower than Val/Met and Met/Met patients (β=−12.17, p=0.041, n=28). This result remained significant after adjusting for the dose of VPA administered in the 48 hours prior to the blood draw (p=0.043). 
     Example 4 
     COMT Genotype Modifies the Relationship Between Proline and Negative Symptom Change in in Bipolar Disorder: 
     The hypothesis that COMT genotype modifies the relationship between proline and negative symptoms across psychiatric illnesses was explored, employing a second patient sample: 43 subjects with bipolar disorder who had completed a BPRS assessment upon admission to the psychiatric ER (visit 1) plus a second BPRS assessment and fasting blood draw during their follow-up visit (mean duration between assessments=9.5±4.6 days). Thus, for this sample the relationship between COMT and proline on the change in symptoms was calculated by the percent reduction in negative symptoms from admission to follow-up. 
     As for the schizophrenia cohort, recruitment of the bipolar sample was not targeted by COMT genotype, but subjects were matched on demographic characteristics (Table 5) and medication use at both study visits (Table 6). The distribution of COMT genotypes was in HWE (χ 2 =0.387, df=1, p&gt;0.05). Due to the finding in schizophrenia that Met allele carriers have a similar response to high proline, and because of the smaller bipolar sample size, Met/Met and Val/Met bipolar groups were pooled for further analysis. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Demographic and Clinical Characteristics of Bipolar Disorder Patients, n = 43 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Met/Met 
                 Val/Met 
                 Val/Val 
                   
               
               
                 Characteristic 
                 n = 5 
                 n = 22 
                 n = 16 
                 Prob a   
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Gender, n (row %) 
                   
                   
                   
                 0.328 
               
               
                 Female 
                 1 (6.2)  
                 11 (68.8) 
                  4 (25.0) 
               
               
                 Male 
                 4 (14.8) 
                 11 (40.7) 
                 12 (44.4) 
               
               
                 Ethnicity, n (row %) 
                   
                   
                   
                 0.450 
               
               
                 African American 
                 0 
                  4 (57.1) 
                  3 (42.9) 
               
               
                 Asian 
                 0 
                 0 
                  1 (100) 
               
               
                 Caucasian 
                 3 (11.5) 
                 13 (50.0) 
                 10 (38.5) 
               
               
                 Hispanic 
                 2 (22.2) 
                  5 (55.6) 
                  2 (22.2) 
               
               
                 Age (years), mean ± SD 
                   34 ± 9.7 
                 32.8 ± 8.4 
                  33.2 ± 11.2 
                 0.933 
               
               
                 Smoking Status b , n (row %) 
                   
                   
                   
                 1.000 
               
               
                 Current or Previous 
                 4 (13.3) 
                 15 (50.0) 
                 11 (36.7) 
               
               
                 Never Smoked 
                 1 (8.3)  
                  6 (50.0) 
                  5 (41.7) 
               
               
                 History of Alcoholism, n (row %) 
                   
                   
                   
                 1.000 
               
               
                 Abuse 
                 1 (7.1)  
                  8 (57.1) 
                  5 (35.7) 
               
               
                 Dependence 
                 1 (12.5) 
                  4 (50.0) 
                  3 (37.5) 
               
               
                 Neither 
                 3 (14.3) 
                 10 (47.6) 
                  8 (38.1) 
               
               
                 Education c , mean ± SD 
                  4.2 ± 2.0 
                  3.8 ± 1.6 
                  4.2 ± 2.0 
                 0.709 
               
               
                 Fasting Plasma Proline d , umol/L 
                 213.6 ± 72.7 
                 205.5 ± 63.2 
                  245.8 ± 123.4 
                 0.669 
               
               
                 Age at Onset, mean ± SD 
                 25.8 ± 2.8 
                 26.4 ± 8.3 
                 24.1 ± 7.8 
                 0.207 
               
               
                 Age at First Hospitalization, mean ± SD a   
                   26 ± 3.2 
                 26.8 ± 9.3 
                 22.9 ± 7.4 
                 0.112 
               
               
                 Days between Symptom Assessments, 
                 10.2 ± 6.2 
                  9.4 ± 3.7 
                  9.5 ± 5.1 
                 0.382 
               
               
                 mean ± SD 
               
               
                   
               
               
                   a P-value values when comparing Met allele carriers to Val/Val patients, calculated by Satterthwaite t-test, Mann-Whitney, Chi-Square or Fisher exact test. 
               
               
                   b n = 42, one subject not reported. 
               
               
                   c Recorded as a continuous variable from the SCID (range 2-8). 
               
               
                   d Sampled at visit 2. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Clinical Characteristics of Bipolar Disorder Patients, n = 43 
               
            
           
           
               
               
               
            
               
                   
                 Admission (Visit 1) 
                 Follow-up (Visit 2) 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 Met/Met 
                 Val/Met 
                 Val/Val 
                   
                 MetMet 
                 Val/Met 
                 ValVal 
                   
               
               
                 Characteristic 
                 n = 5 
                 n = 22 
                 n = 16 
                 Prob a   
                 n = 5 
                 n = 22 
                 n = 16 
                 Prob a   
               
               
                   
               
               
                 Brief Psychiatric 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Rating Scale b   
               
               
                 Total Symptoms, 
                  42 ± 7.3 
                 36.3 ± 5.9 
                 36.4 ± 4.7 
                 0.592 
                 34.8 ± 8.8 
                 25.9 ± 5.8 
                 27.4 ± 5.2 
                 0.772 
               
               
                 mean ± SD 
               
               
                 Negative Symptoms c , 
                 9.0 ± 5.1 
                  6.3 ± 2.2 
                  6.2 ± 1.7 
                 0.872 
                  6.0 ± 1.4 
                  5.6 ± 0.9 
                  5.6 ± 1.0 
                 0.711 
               
               
                 mean ± SD 
               
               
                 Positive Symptoms d , 
                 24.6 ± 5.0  
                 18.7 ± 6.2 
                 18.2 ± 6.2 
                 0.457 
                 18.4 ± 5.3 
                 12.4 ± 4.8 
                 13.7 ± 4.2 
                 0.553 
               
               
                 mean ± SD 
               
               
                 Psychosis e : yes, n 
                 4 (13.3) 
                 14 (46.7)  
                 12 (40)   
                 0.735 
               
               
                 (row %) 
               
               
                 Neuroleptic (NL) 
               
               
                 Medications 
               
               
                 NL Type, n (row %) 
                   
                   
                   
                 1.000 
                   
                   
                   
                 0.745 
               
               
                 Typical only 
                 2 (22.2) 
                 4 (44.4) 
                 3 (33.3) 
                   
                 0 
                 0 
                 1 (100)  
               
               
                 Atypical only 
                 1 (12.5) 
                 4 (50.0) 
                 3 (37.5) 
                   
                 3 (9.7) 
                 17 (54.8)  
                 11 (35.5)  
               
               
                 Both 
                 0 
                 3 (75)   
                 1 (25)   
                   
                  2 (40.0) 
                 1 (20.0) 
                 2 (40.0) 
               
               
                 None 
                 2 (9.1)  
                 11 (50.0)  
                 9 (40.9) 
                   
                 0 
                 4 (66.7) 
                 2 (33.3) 
               
               
                 Daily CPZE dose f , 
                 282.3 ± 202.1 
                  284.1 ± 109.7 
                 239.3 ± 81.5 
                 0.403 
                  566.7 ± 372.1 
                  344.4 ± 162.6 
                  362.3 ± 202.6 
                 0.863 
               
               
                 mean ± SD 
               
               
                 Total number of NLs, 
                   
                   
                   
                 0.906 
                   
                   
                   
                 0.731 
               
               
                 n (row %) 
               
               
                 0 
                 2 (9.1)  
                 11 (50)   
                 9 (40.9) 
                   
                 0 
                 4 (66.7) 
                 2 (33.3) 
               
               
                 1 
                 3 (17.6) 
                 8 (47.1) 
                 6 (35.3) 
                   
                 2 (7.1) 
                 16 (57.1)  
                 10 (35.7)  
               
               
                 2 
                 0 
                 3 (75.0) 
                 1 (25.0) 
                   
                  3 (37.5) 
                 2 (25)   
                 3 (37.5) 
               
               
                 Mood Stabilizing 
               
               
                 Medications 
               
               
                 Total number of 
                   
                   
                   
                 0.282 
                   
                   
                   
                 0.785 
               
               
                 mood stabilizers, 
               
               
                 n (row %) 
               
               
                 0 
                 5 (12.5) 
                 19 (47.5)  
                 16 (40.0)  
                   
                 0 
                 1 (100)  
                 0 
               
               
                 1 
                 0 
                 3 (100)  
                 0 
                   
                 3 (8.3) 
                 20 (55.6)  
                 13 (36.1)  
               
               
                 2 
                 0 
                 0 
                 0 
                   
                  2 (33.3) 
                 1 (16.7) 
                 3 (50)   
               
               
                 VPA: yes, n (row %) 
                 0 
                 1 (100)  
                 0 
                 1.000 
                 2 (9.5) 
                 11 (52.4)  
                 8 (38.1) 
                 1.000 
               
               
                 Other Medications 
               
               
                 Benzodiazapines: 
                 3 (15.8) 
                 10 (52.6)  
                 6 (31.6) 
                 0.542 
                  4 (22.2) 
                 4 (22.2) 
                 10 (55.6)  
                 0.055 
               
               
                 yes, n (row %) 
               
               
                 Antidepressants: yes, 
                 0 
                 2 (66.7) 
                 1 (33.3) 
                 1.000 
                 1 (5.6) 
                 7 (38.9) 
                 10 (55.6)  
                 0.055 
               
               
                 n (row %) 
               
               
                   
               
               
                   a P-value values when comparing M allele carriers to ValVal patients, calculated by Satterthwaite t-test, Mann-Whitney, Chi-Square or Fisher exact test. 
               
               
                   b BPRS = Brief Psychiatric Rating Scale. 
               
               
                   c Negative Symptoms (BPRS items 3 + 13 + 14 + 16 + 18) 
               
               
                   d Positive Symptoms (BPRS items 4 + 7 + 8 + 10 + 11 + 12 + 15 + 17) 
               
               
                   e Psychosis determined as current or previous psychotic illness at admission only. 
               
               
                   f Chlorpromazine (CPZ) equivalent dose. 
               
            
           
         
       
     
     A significant interaction was observed between COMT and fasting peripheral proline on the percent change in negative symptoms (n=43, interaction β coefficient=−0.0017, p=0.04). As shown in  FIG. 4 , high proline was associated with a greater reduction of negative symptoms for Val/Val bipolar patients but conversely, Met carrier patients with high proline levels had, in general, either no change or a positive change in negative symptoms, suggesting a worsening of symptoms over time. Again, possible confounds were assessed (Table 7). Regarding medication, while there was no relationship between the percent change in negative symptoms and mood stabilizer use or neuroleptic dose, covariate analysis indicated that neuroleptic type and benzodiazepine use, plus the duration between visits, were predictors of the change in negative symptoms, as were the demographic characteristics of ethnicity and gender (p&lt;0.1, Table 7). These covariates were taken forward to multivariate models (Table 4). Sequential Wald Tests were performed, determining goodness-of-fit, with the proline-COMT interaction remaining significant after adjustment for gender in the final model (interaction β coefficient=−0.0021, p=0.0007). 
     As found with the schizophrenia sample, bipolar VPA-treated patients had significantly higher fasting plasma proline than those who did not receive VPA ( FIG. 5 ). However, while Val/Val treated patients had a greater overall reduction in negative symptoms compared to Met carriers, this result did not reach significance, possibly due to the variability observed and the small sample ( FIG. 5 ). There was no significant effect modification of COMT on the relationship between proline and percent change in positive symptoms (interaction β=0.0005, p=0.950), or percent change in total BPRS scores (interaction β=−0.0009, p=0.153), again suggesting specificity of the relationship between COMT and proline to negative symptoms. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Bivariate Association Between Bipolar Disorder Patient 
               
               
                 Demographic and Clinical Characteristics, with 
               
               
                 Percent Change in Negative Symptoms, n = 43 
               
            
           
           
               
               
               
            
               
                 Characteristic (at Visit 2) 
                 β (95% CI) 
                 Prob a   
               
               
                   
               
            
           
           
               
               
               
            
               
                 Gender b   
                  1.359 (0.003, 0.268) 
                 0.045* 
               
               
                 Ethnicity c   
               
               
                 African American v Caucasian d   
                 −0.048 (−0.022, 0.121) 
                 0.566 
               
               
                 African American v Hispanic 
                 −0.272 (−0.473, −0.071) 
                 0.009* 
               
               
                 Age 
                  0.003 (−0.004, 0.010) 
                 0.369 
               
               
                 Education e   
                  0.013 (−0.026, 0.051) 
                 0.513 
               
               
                 Alcohol Dependence/abuse b   
               
               
                 None v Abuse 
                 −0.020 (−0.174, 0.133) 
                 0.790 
               
               
                 None v Dependence 
                 −0.055 (−0.240, 0.130) 
                 0.554 
               
               
                 Smoking Status f   
                 −0.104 (−0.045, 0.253) 
                 0.165 
               
               
                 Duration (days) between 
                  0.013 (−0.002, 0.028) 
                 0.082* 
               
               
                 symptom assessments 
               
               
                 Daily CPZE dose g   
                 −0.000 (−0.000, 0.000) 
                 0.607 
               
               
                 Neuroleptic (NL) Type b   
               
               
                 None v Atypical 
                 −0.091 (−0.285, 0.103) 
                 0.348 
               
               
                 None v Typical 
                 −0.006 (−0.476, 0.465) 
                 0.981 
               
               
                 None v both 
                 −0.230 (−0.494, 0.033) 
                 0.085* 
               
               
                 Total Number of NLs Administered h   
                 −0.074 (−0.192, 0.043) 
                 0.209 
               
               
                 Total Number of Mood Stabilizers 
                 −0.050 (−0.154, 0.054) 
                 0.338 
               
               
                 Administered i   
               
               
                 VPA Treatment 
                 −0.013 (−0.148, 0.122) 
                 0.845 
               
               
                 Benzodiazapines 
                 −0.120 (−0.251, 0.011) 
                 0.072* 
               
               
                 Antidepressants 
                  0.004 (−0.133, 0.140) 
                 0.958 
               
               
                   
               
               
                   a *Taken forward into multivariate model. 
               
               
                   b Binary variable: Male v female. 
               
               
                   c For categorical analysis the reference category is the first level listed for each variable. 
               
               
                   d Includes n = 1 Asian subject. Parameter estimates did not change following the removal of this subject, and so they were included in all final models. 
               
               
                   e Recorded as a continuous variable from the SCID (range 2-8). 
               
               
                   f Binary variable: Never v current or previous smokers, n = 42 (as one subject did not report smoking status). 
               
               
                   g Chlorpromazine (CPZ) equivalent dose, n = 37 (as six subjects did not receive a NL). 
               
               
                   h Continuous variable with three levels (none, one or two), n = 42 (as only subject was administered &gt;two NLs). 
               
               
                   i Binary variable: one v two, n = 42 (as one subject did not receive a mood stabilizer). 
               
            
           
         
       
     
     Example 5 
     Discussion 
     The data presented herein demonstrate that fasting peripheral proline and COMT Val 158 Met genotype predict negative symptom severity across psychiatric diagnoses. Specifically, evidence is presented that in schizophrenia patients with the Val/Val genotype (encoding the high activity COMT enzyme), high proline was associated with lower levels of negative symptoms. As proline rose across the Val/Val patient sample, negative symptoms decreased. Conversely, Met allele carriers displayed the opposite relationship, exhibiting significantly more negative symptoms as proline levels rose. Over the range of fasting proline in the schizophrenia sample (87-502 μM), this represents a significant and clinically relevant difference in negative symptoms between COMT genotype groups. 
     VPA upregulates circulating proline (Jacquet et al., 2005) and VPA-treated schizophrenia Val/Val patients had significantly less negative symptoms than VPA-treated Met allele patients, likely due to the impact of VPA on proline level. Interestingly, the relationship between proline, COMT and negative symptoms was consistent across the entire schizophrenia sample, whether subjects received VPA or not, suggesting that the source of circulating proline is less important than the actual level in predicting symptoms. This data has implications for treatment decisions, because proline-modulating medications such as VPA, which is very commonly used to treat bipolar disorder and also schizophrenia, may have differential benefits on negative symptoms and conversely, detrimental effects, based upon the Val 158 Met genotype. 
     In a second sample, the interaction between COMT and proline on negative symptom change was explored in patients with bipolar disorder (using the BPRS negative symptom subscale). Supporting the earlier schizophrenia finding, a significant interaction was observed between proline and COMT: high proline was associated with improvement of negative symptoms in homozygous Val/Val bipolar patients, while high proline in Met allele carriers was associated with less improvement or an increase in negative symptom severity. This finding was not confounded by medication use, the duration of time between assessments, or demographic characteristics of the bipolar sample. Interestingly, the bipolar patients did not have proline levels significantly higher than controls, suggesting that proline may impact negative symptoms and their severity, but not bipolar disorder risk. 
     The present disclosure is believed to be the first to document that proline and COMT interact to predict negative symptom outcomes in psychiatric and other disorders. The finding of a detrimental effect of high proline in combination with the COMT Met allele on schizophrenia and bipolar disorder negative symptoms, is in part supported by studies of 22q11DS patients, who have an increased risk of psychosis (albeit exhibiting positive symptoms (Raux et al., 2007)) plus a neurophysiological visual sensory deficit (Vorstman et al., 2009), when carrying the Met allele in the presence of high proline. 
     This finding that high proline is protective in Val/Val patients with schizophrenia and bipolar disorder is novel and significant. Intriguingly, Zarchi et al. (2013), reported the protective effect of a PRODH variant (the Tryptophan (Trp) allele of the Arg 185 Trp polymorphism) on a neurophysiological measure (MMN) in COMT Val 22q11DS patients. Since the Trp allele exhibits decreased PDX activity in vitro (Bender et al., 2005), Zarchi et al., discussed either an opposite effect of this allele in vivo, or alternatively that the Arg 185 Trp polymorphism is in linkage disequilibrium with another functional SNP; in each circumstance likely resulting in increased PDX activity and low peripheral proline. The data disclosed herein suggests the opposite to that interpretation: that high proline is actually protective in hem izygous 22q11DS patients with the Val genotype, with regards to MMN. 
     Putative CNS roles of proline have been described both in terms of its potential as a neurotransmitter, suggested by its uptake into and direct synthesis within synaptosomes and its release at the synapse after K+ induced depolarization (Phang et al., 2001; Nickolson, 1982; Yoneda and Roberts, 1982; Nadler, 1987), as well as a neuromodulator of neurotransmitter systems, suggested by the presence of high-affinity proline transporters in glutamatergic neurons (Phang et al., 2001; Renick et al., 1999; Cohen and Nadler, 1997a; Cohen and Nadler, 1997b), and the enhancements of glutamatergic and prefrontal DA transmission in the presence of Prodh deficiency and elevated proline (Paterlini et al., 2005). Although the mechanism by which proline elevation may impact neurotransmission requires further investigation, it is apparent from the Prodh null model (Gogos et al., 1999; Paterlini et al., 2005) and the human hyperprolinemias (Phang et al., 2001) that elevated proline can be detrimental in the CNS. In schizophrenia and bipolar disorder, carrying the Met allele may further accentuate proline&#39;s toxicity. In this model, enhanced DA-transmission in the PFC as a result of excess proline is exacerbated by low COMT activity and concomitant higher prefrontal DA availability, ultimately resulting in a frontal hyperdopaminergic state that mimics that of the Prodh null mouse (Paterlini et al., 2005; and as reviewed in Drew et al., 2011). 
     A hyperdopaminergic model influencing negative symptom severity is somewhat counterintuitive, given that negative symptoms are generally considered to arise from deficient mesocortical DA stimulation. However, COMT is involved in maintaining PFC cognitive stability (Bilder et al., 2004; Turnbridge et al., 2006), and in situations of high cortical DA concentrations and D 1  receptor stimulation (likely present in Met/Met and to a lesser degree Val/Met psychiatric patients), enhanced cognitive stability of neuronal network activation has been theorized by Bilder et al. (2004) to result in a cognitive rigidity that may increase the likelihood of negative symptoms. Thus, the Met allele may be less effective in alleviating the increased dopaminergic tone in schizophrenia and bipolar disorder patients with elevated proline, significantly impacting negative symptoms or at least the persistence of negative symptoms and their improvement after treatment. 
     Conversely, as disclosed herein, proline elevation beneficially influences negative symptom severity in Val/Val patients. In a COMT Val homozygous state, high enzymatic activity in the PFC would likely reduce prefrontal DA, limiting D 1  receptor-mediated excitation (Bilder et al., 2004; Turnbridge et al., 2006). Speculatively, proline elevation may increase prefrontal DA signaling, through interference with glutamatergic pathways (Paterlini et al., 2005), reducing vulnerability to a prefrontal hypodopaminergic state in Val/Val patients (Bilder et al., 2004). Taken together these models suggest that negative symptoms are significantly impacted in conditions of both hyper- or hypo-DA activity. 
     Interestingly, no relationship was found between COMT and proline on positive symptoms. Positive symptoms are considered to arise from hyperactive subcortical mesolimbic projections, and the current finding is consistent with the action of proline in murine cortical but not striatal DA potentiation (Paterlini et al., 2005). Additionally, DA transporters are relatively sparse in the PFC (Lewis et al., 2001), and the removal of DA there may be more impacted by COMT activity and the interaction with proline, as compared to subcortical regions. 
     Some study limitations exist: in the schizophrenia sample, proline was measured and symptoms assessed cross-sectionally. Thus the findings may be confounded by enrollment differences across genotypes. However, negative symptoms were not significantly different between genotypes, there was no significant main effect of COMT on negative symptoms, and the length of hospitalization prior to symptom assessment had no relationship with negative symptoms, suggesting that the cross-sectional nature of the study did not confound the results. Additionally, while the bipolar study allowed investigation of symptom change, the bipolar sample size was smaller and negative symptoms assessed using only a subscale of the BPRS. Further research would therefore benefit from a longitudinal approach, investigating the interaction between proline and COMT on the change in negative symptoms assessed via the SANS, in a large sample of both schizophrenia and bipolar disorder patients. 
     Nonetheless, there are currently no medications approved for the treatment of negative symptoms in psychiatric illness, which are associated with poor functional outcomes and quality of life, are highly persistent, and are a great burden for caregivers (Blanchard et al., 2011). The finding of a beneficial effect on negative symptoms of high proline in Val/Val patients suggests that personalization of treatments based upon a patient&#39;s COMT genotype, for the purpose of up- or down-regulating proline level, holds promise as a pharmacogenomics approach to intervene and target this unaddressed symptom domain. 
     Example 6 
     Relationship Between Change in Proline and Negative Symptoms: 
     Preliminary data also suggests that a change in proline level is directly related to change in negative symptoms. Specifically, twelve bipolar disorder patients had a pre- and post-medication fasting blood draw (with proline measured), plus pre- and post-assessment. Of these, ten were Met allele carriers (Met/Met or Val/Met). Findings suggest that high proline is associated with no improvement or a worsening of symptoms in the presence of high proline. Thus, it was expected that for these subjects, an increase in proline would be related to a worsening of symptoms. Testing this hypothesis, a strong positive relationship was found between the change in proline and the percent change in negative symptoms (see  FIG. 6 ). As proline increased (change in proline was calculated as the post medication proline level−pre-medication proline level, and for all ten subjects proline increased), a positive change was observed in negative symptoms, suggesting a worsening of symptoms over time (spearman&#39;s rho=0.45), although this result did not reach significance (p=0.19), likely due to the small sample size. 
     Only two subjects were Val/Val homozygotes with both pre- and post-medication values. Interestingly, one subject whose proline went down (from 167 μM to 119 μM) had no change in negative symptoms. However, the other subject, whose proline went up (from 206 μM to 332 μM), had a corresponding decrease in negative symptoms (from a score of 8 to 6). Again, this supports the hypothesis that high proline is good for Val/Val homozygotes. 
     However, valproate increases peripheral proline, so it can be assumed that all Val/Val patients treated with Valproate (n=8) had an increase in peripheral proline between blood draws (regardless of whether the blood draw at visit one was fasting). Therefore, using this subsample, there was seen a negative relationship between the change in proline and symptoms (spearman&#39;s rho=−0.4), although this result again did not reach significance likely due to the small sample size (p=0.3). 
     Example 7 
     Proline and COMT in Other Disorders: 
     Pomara et al. (1992) showed elevated cerebrospinal fluid (CSF) proline level in Alzheimers disease (AD). Patients with AD are also known to display negative symptoms. Treatment to modulate proline levels based upon COMT Val 158 Met genotype would be beneficial to control those symptoms in AD. 
     Ethanol increases circulating proline levels, and comorbid alcohol use disorder is the most common comorbidity in schizophrenia (Drake and Mueser, 2002), and is also common in bipolar disorder (Sonne and Brady, 2002). Up- or down-regulation of proline level may exacerbate negative symptoms or conversely improve them, depending on COMT genotype. Alcohol use may be a form of self-medication that could be replaced by other proline modulation methods/treatments. Recently, differential effects were found of alcohol abuse or dependence frequency based on genotype (COMT Val/Val subjects were 2.4 times more likely to report alcohol abuse and/or dependence than Met allele patients, p=0.09, unpublished). 
     Susceptibility to alcohol abuse and/or dependence may be related to differential effects on mood and/or pleasure-ability based upon proline level and COMT genotype. Treatments to alter proline level based on COMT genotype may be useful for the treatment of alcohol use disorders and potentially for gambling disorders (Guillot et al., 2015). 
     Example 8 
     Proline and COMT in Alcohol Use Disorder (AUD): 
     Comorbidity of Alcohol Use Disorder (AUD) with schizophrenia (SZ) is highly prevalent at over 33% of SZ patients. Comorbidity is associated with particularly unfavorable outcomes including raising mortality risk and treatment non-adherence. Of particular relevance, some SZ patients have reported a decrease of symptoms, including negative symptoms, following alcohol ingestion. This is important because the negative symptoms of SZ (loss of motivation, flattening of emotional responses, decreased speech and activity, and social withdrawal), are disabling and persistent, and significantly contribute to the immense personal and economic costs of SZ. No medications are FDA-approved for treatment of negative symptoms in SZ. 
     Proline is a precursor of the neurotransmitter glutamate and may function as a CNS neuromodulator. Elevated proline stimulates dopamine signaling in murine models. Catechol-O-methyltransferase (COMT) catalyzes deactivation of neurotransmitters including dopamine. In our recent, replicated, study we found that fasting plasma proline levels (which reflect CNS levels) and the COMT Val158Met functional polymorphism (high/low enzyme activity) significantly interact, predicting negative symptom outcomes in patients with severe psychiatric illness. Specifically, in Val/Val patients, high proline is protective with low negative symptom severity or a greater negative symptom reduction over time. Conversely, COMT Met carriers demonstrated the opposite: significantly more negative symptoms or less symptom improvement as proline increased. 
     Alcohol ingestion upregulates circulating proline, in those with a current or past AUD, and thus we hypothesized that comorbid patients self-medicate with alcohol to relieve their negative symptoms; predicting more frequent comorbid AUD in Val/Val SZ patients. In a preliminary study we indeed found a strong trend as compared to Met allele carriers for whom alcohol-induced proline elevation would be detrimental (p=0.06, 2-tailed). This finding is important because sodium valproate (VPA), prescribed to ˜35% of SZ inpatients, is also a strong up-regulator of proline levels. We found a strong trend towards significance for an interaction between VPA treatment and AUD on cross-sectional proline levels (interaction p=0.050); with VPA vastly boosting proline levels in Val/Val patients with AUD, but not significantly in VPA-treated patients without an AUD (data not shown). We propose personalized VPA treatment or treatment with proline or modulators that increase proline levels, for negative symptoms in comorbid AUD and neuropsychiatric disorders including schizophrenia patients who carry the Val/Val genotype, to relieve negative symptoms and assist in maintaining abstinence. 
     Example 9 
     Proline and COMT in Alzheimer&#39;s Disease (AD)/Traumatic Brain Injury (TBI): 
     Neuropsychiatric symptoms such as apathy are frequently described in patients with Alzheimer&#39;s disease (AD), as well as those who have sustained a traumatic brain injury (TBI). In fact, reports have suggested that close to one half of all AD and TBI patients&#39; exhibit apathy (Brodaty et al. 2015; Karttunen et al. 2011; Hwang et al. 2004; Lyketsos et al. 2011), which is characterized by the loss of motivation to participate in activities, social withdrawal, and emotional indifference and these symptoms often present in incipient AD (including MCI) (Leoutsakos et al. 2015; Van Dam et al. 2016) or within the first year after brain injury (Stefan et al. 2016). Apathy and related symptoms contribute substantially to the huge personal and economic costs for individuals living with AD and TBI: Apathy can disrupt patients&#39; participation in family life and social integration, and can lead to more intensive utilization of health care services (Arnould et al. 2015; Cattelani et al. 2008). Furthermore, apathy in AD is associated with a rapid course of functional and cognitive decline (Benoit et al. 2008; Lechowski et al. 2009; Landes et al. 2005; Leoutsakos et al. 2015), and in TBI patients, negatively impacts rehabilitation (Starkstein et al. 2014). Of relevance, substantial caregiver burden and distress have been significantly associated with the presence and severity of apathy (Karttunen et al. 2011; Lyketsos et al. 2011; Starkstein et al. 2014; Arnould et al. 2015; Fauth et al. 2014). 
     Apathy is a “negative” neuropsychiatric symptom. Although commonly considered a major symptom domain of psychiatric illness, the full spectrum of negative symptoms can also present in patients with dementia (Reichman et al. 1996; Galynker et al. 1997; Negron et al. 2000; Galynker et al. 2000; Vercelletto et al. 2002; de Jonghe et al. 2003) and constitutes an independent behavioral dimension that is not an outcome of depression and/or cognitive status (Reichman et al. 1996; Galynker et al. 1997; de Jonghe et al. 2003). 
     Intriguingly, it has been suggested that targeting of these symptoms in AD may extend the time to conversion from MCI (Ismail et al. 2016) and possibly positively alter the trajectory of the disease process (Forlenza et al. 2017). However, there are no approved treatments for negative symptoms in AD or TBI, and thus there is clearly a need for new research into interventions that target neuropsychiatric symptoms of AD and TBI, in particular negative symptoms, to improve the quality of life for individuals living with TBI and AD, and also to alleviate the burden on their caregivers. 
     There is evidence of increased CNS and peripheral proline levels in patients with AD (Pomara et al. 1992; Molina et al. 1998; Trushina et al. 2013). We propose and will investigate that the proline x COMT interaction and its impact on negative symptoms, either beneficial or detrimental, as previously observed in psychiatric disorders, is generalizable across neuropsychiatric diseases including AD and TBI. 
     Example 10 
     Relationship Between Negative Symptoms and VPA Level: 
     The relationship between blood levels of VPA and negative symptoms was investigated by COMT genotype. It was hypothesized that those with the Met allele and high levels of blood VPA would have a lower % negative symptom change, i.e. a positive % change, indicating increased negative symptoms, due to exacerbation by increased proline level. Conversely, Val/Val patients would be expected to have a greater % decrease in negative symptoms as levels of VPA rose. As hypothesized, and as shown in  FIG. 7 , negative symptoms generally either increased or did not change after treatment onset (red points) for Met allele carriers as VPA levels rose, as compared to Val/Val patients. A blood level of 50 μg/ml of VPA is considered the lower end of the therapeutic range: of the Met allele carriers within this range, only 2 out of 9 showed improvement in negative symptoms, as opposed to 5 out of 7 Val/Val patients (p=0.07). 
     Example 11 
     Proline may function as a neuromodulator via stimulation or alteration of neuronal glutamate and/or GABA signaling, which may underlie its effect on negative and other neuropsychiatric symptoms (Clelland et al., 2016; Crabtree et al., 2016). Molecules that can modulate neuronal glutamate signaling including NMDA receptor and/or glutamatergic signaling functions, and have been considered and/or tested in clinical trials in psychiatric disorders include glycine, D-serine, D-cycloserine and bitopterin (Roche RG1678; RO-4917838), sarcosine, SSR103800, Org 25935 and betaine. These are thought to alter glutamate receptor activity or function either directly or indirectly via modulation of the concentration of glycine and/or function of the glycine binding site. 
     Considering that clinical studies of molecules also thought to influence glutamate signaling have had mixed results, an initial exploratory analysis was performed of fasting plasma glycine and 1-serine and an interaction with COMT genotype on negative symptoms of schizophrenia. Plasma glycine concentrations reflect CNS levels (Jiménez-Jiménez et al., 1998; Scholl-Bürgi et al., 2008; Luykx et al., 2013) and CSF D-serine, which is derived from L-serine via serine racemase, is significantly correlated with plasma L-serine (Luykx et al., 2013; Hashimoto et al., 2003). 
     In a sample of schizophrenia patients (n=95), fasting plasma glycine and 1-serine significantly predicted increased negative symptoms in those subjects with the COMT Val/Met or Met/Met genotypes (glycine r=0.48, p=0.0003, n=53; 1-serine r=0.32, p=0.02, n=53), but not in Val/Val carriers (glycine r=−0.05, p=0.78, n=42; 1-serine r=−0.12, p=0.46, n=42). Following on from this, in regression analysis any significant effect of glycine was tested for after adjusting for the potential confounding effect of proline. A significant effect of glycine on negative symptoms remained (p=0.013) with medium effect size (partial eta 2 =0.116). As for proline, as glycine increased, so did negative symptoms in Met allele carrier patients. 
     In addition, analysis of valproate versus non-valproate-treated subjects indicated that valproate significantly upregulates fasting glycine levels (268 uM no valp n=64, 361 uM valp n=31, p=0.0007) and L-serine levels (103 uM no valp n=64, 117 uM valp n=31, p=0.004). 
     Given these findings of glycine and serine interactions with COMT, the interaction of COMT Val 158 Met genotype with glycine on negative symptoms therefore also likely occurs when glycine modulators, including those listed above, are used in psychiatric and neuropsychiatric disorders. 
     As some of the molecules listed above have been extensively tested in clinical trials, reanalysis of the trial data and/or new trials accounting for COMT genotype when determining efficacy, may lead to evidence of therapeutic efficacy that has been previously undetected. 
     Trials of the molecules listed above for the treatment of psychiatric, neuropsychiatric, psychotic, mood and personality disorders, and symptoms thereof such as negative symptoms, should therefore be analyzed to account for the interaction of individuals&#39; COMT Val 158 Met genotype with glycine and (L- and/or D-) serine levels (and/or with potentially glutamate and/or GABA), with the expectation that COMT Val/Val genotype individuals will respond differently from Met allele carriers, and the failure of clinical trials to achieve efficacy may be due to patients not being chosen based on their COMT genotype (and thus whether they would benefit or be harmed by such treatment). In recent studies, we have identified that the proline modulator, LX6171, an SLC6A7 (PROT) transporter inhibitor, may be useful for treatment of COMT Val 158 /Val, or for COMT Met 158 Met or COMT Val 158 Met carriers, and may act via increased synaptic proline and/or decreased gamma-aminobutyric acid (GABA) synthesis (data not shown). 
     
       
         
           
               
             
               
                 TABLE S1 
               
               
                   
               
               
                 Molecules that regulate genes or gene products relevant to proline transport and metabolism. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 A1. Molecules that upregulate PRODH: 
               
            
           
           
               
               
               
            
               
                 gefitinib 
                 harman 
                 Dimethylformamide 
               
               
                 Pyrilamine 
                 Fluocinolone Acetonide 
                 cephalonium 
               
               
                 Phenacetin 
                 Methylnitrosourea 
                 Ketoconazole 
               
               
                 dexibuprofen 
                 Cortisone 
                 Ceftriaxone 
               
               
                 aristolochic acid I 
                 Mycophenolic Acid 
                 GW 501516 
               
               
                 Betamethasone 
                 Rifabutin 
                 Caffeine 
               
               
                 Methotrexate 
                 Fluphenazine 
                 dihydroquinghaosu 
               
               
                 piperaquine 
                 Isotretinoin 
                 Naproxen 
               
               
                 leflunomide 
                 bromodichloromethane 
                 Itraconazole 
               
               
                 Roxarsone 
                 Dicumarol 
                 fluvastatin 
               
               
                 Hydrocortisone 
                 diindolylmethane 
                 cyclonite 
               
               
                 Gliclazide 
                 cerivastatin 
                 Digoxin 
               
               
                 Doxorubicin 
                 Hexachlorophene 
                 Ifosfamide 
               
               
                 meloxicam 
                 Melatonin 
                 Malathion 
               
               
                 Triiodothyronine 
                 Sulfacetamide 
                 Tacrolimus 
               
               
                 Fluoxetine 
                 Desoxycorticosterone 
                 chloroxylenol 
               
               
                 genipin 
                 Trenbolone Acetate, (17beta)-isomer 
                 phenacemide 
               
               
                 erlotinib 
                 Chlorpropamide 
                 arsenic trioxide 
               
               
                 decitabine 
                 Terfenadine 
                 Paraquat 
               
               
                 Dantrolene 
                 Cymarine 
                 quelamycin 
               
               
                 Maprotiline 
                 2,2-bis(bromomethyl)-1,3-propanediol 
                 Ethamsylate 
               
               
                 Dexamethasone 
                 AICA ribonucleotide 
                 methyl salicylate 
               
               
                 Doxazosin 
                 Methylprednisolone 
                 loxoprofen 
               
               
                 pipenzolate 
                 Epirubicin 
                 monobenzone 
               
               
                 Valproic Acid 
                 fluticasone 
                 naphthalene 
               
               
                 Ofloxacin 
                 enrofloxacin 
                 Hemicholinium 3 
               
               
                 Acrolein 
                 4-dichlorobenzene 
                 4,4′-diaminodiphenylmethane 
               
               
                 depudecin 
                 1,3-dichlorobenzene 
                 riddelliine 
               
               
                 halofuginone 
                 Ethyl Methanesulfonate 
                 Clioquinol 
               
               
                 p-Aminohippuric Acid 
                 Antipyrine 
                 N-benzyladenine 
               
               
                 Oxprenolol 
                 Diflunisal 
                 Cyclosporine 
               
               
                 Bithionol 
                 loracarbef 
                 ebastine 
               
               
                 Chlorpyrifos 
                 oxiconazole 
                 Sulindac 
               
               
                 Amoxapine 
                 Oxyquinoline 
                 Thioguanine 
               
               
                 Pyrethrins 
                 phenethyl isothiocyanate 
                 Ultraviolet Rays 
               
               
                 amprenavir 
                 Cisapride 
                 Bromisovalum 
               
               
                 oxcarbazepine 
                 Thioctic Acid 
                 blebbistatin 
               
               
                 trichlorofluoromethane 
                 Methyldopa 
                 Clemastine 
               
               
                 Altretamine 
                 Gold 
                 Hydrochloric Acid 
               
               
                 9-(2-hydroxy-3-nonyl)adenine 
                 torsemide 
                 Etidronic Acid 
               
               
                 Bisacodyl 
                 Sulfisoxazole 
                 Clobetasol 
               
               
                 Erythromycin 
                 1-Methyl-4-phenyl-1,2,3,6- 
                 Pimozide 
               
               
                 Ethylsuccinate 
                 tetrahydropyridine 
                   
               
               
                 Betahistine 
                 Iproniazid 
                 sodium arsenite 
               
               
                 valdecoxib 
                 oxybutynin 
                 Promazine 
               
               
                 letrozole 
                 4′-N-benzoylstaurosporine 
                 Trichloroethylene 
               
               
                 4-octylphenol 
                 naringin 
                 Hydralazine 
               
               
                 dibenzazepine 
                 Gallamine Triethiodide 
                 Flavoxate 
               
               
                 Xylazine 
                 Terazosin 
                 Chlorpromazine 
               
               
                 acetylleucine 
                 Meclofenoxate 
                 N-Methyl-3,4- 
               
               
                   
                   
                 methylenedioxyamphetamine 
               
               
                 Acetazolamide 
                 Calcium 
                 Cephalexin 
               
               
                 Saquinavir 
                 Etoposide 
                 Sulpiride 
               
               
                 nabumetone 
                 Luteolin 
                 Metyrapone 
               
               
                 Glipizide 
                 Trimetazidine 
                 Foscarnet 
               
               
                 hexachlorobutadiene 
                 adiphenine 
                 lapatinib 
               
               
                 n-hexanal 
                 Trichlormethiazide 
                 lamotrigine 
               
               
                 benoxinate 
                 8-Bromo Cyclic Adenosine 
                 Nitrazepam 
               
               
                   
                 Monophosphate 
                   
               
               
                 Moxisylyte 
                 N-(2-cyclohexyloxy-4- 
                 fipexide 
               
               
                   
                 nitrophenyl)methanesulfonamide 
                   
               
               
                 Y 27632 
                 Interleukins 
                 Mianserin 
               
               
                 Amiloride 
                 Sulfadimethoxine 
                 Amikacin 
               
               
                 1,1,1-trichloroethane 
                 Lactic Acid 
                 Rolipram 
               
               
                 Tobramycin 
                 oxaliplatin 
                 Buspirone 
               
               
                 Lithium Chloride 
                 carbinoxamine 
                 Cisplatin 
               
               
                 gabapentin 
                 Choline 
                 Naphazoline 
               
               
                 Cefuroxime 
                 Flurbiprofen 
                 anisindione 
               
               
                 oxaprozin 
                 Cholecalciferol 
                 Dexfenfluramine 
               
               
                 rescinnamine 
                 Pivampicillin 
                 Plicamycin 
               
               
                 Dicyclomine  
                 laudanosine 
                 Antibodies, Monoclonal 
               
               
                 trichostatin A 
                 Daunorubicin 
                 vesamicol 
               
               
                 Ketoprofen 
                 oxolamine 
                 Captopril 
               
               
                 Atovaquone 
                 Fluorouracil 
                 Furosemide 
               
               
                 2-amino-1-methyl-6- 
                 Neomycin 
                 carbetapentane 
               
               
                 phenylimidazo(4,5-b)pyridine 
                   
                   
               
               
                 Isoflurophate 
                 Prochlorperazine 
                 Alprenolol 
               
               
                 olanzapine 
                 Oxymetazoline 
                 Acarbose 
               
               
                 Metaraminol 
                 Levamisole 
                 Trifluridine 
               
               
                 oltipraz 
                 arsenic acid 
                 candesartan 
               
               
                 Sulfamethoxazole 
                 vorinostat 
                 Metoclopramide 
               
               
                 Prazosin 
                 Dizocilpine Maleate 
                 2-(4-morpholinyl)-8-phenyl- 
               
               
                   
                   
                 4H-1-benzopyran-4-one 
               
               
                 Metoprolol 
                 Angiotensin-Converting Enzyme Inhibitors 
                 imatinib 
               
               
                 Phenelzine 
                 Risperidone 
                 Terbutaline 
               
               
                 Harmaline 
                 Fluspirilene 
                 chelidonine 
               
               
                 irinotecan 
                 6-thioguanosine 
                 Imipramine 
               
               
                 Vincristine 
                 Atenolol 
                 Haloperidol 
               
               
                 2,2′-Dipyridyl 
                 Puromycin Aminonucleoside 
                 Domperidone 
               
               
                 Fenoprofen 
                 Dobutamine 
                 Norfloxacin 
               
               
                 3,3′,4′,5-tetrachlorosalicylanilide 
                 Hydroxyurea 
                 Diltiazem 
               
               
                 Dichlorvos 
                 Felodipine 
                 N-Methylaspartate 
               
               
                 Dyphylline 
                 Zidovudine 
                 sodium selenate 
               
               
                 Clarithromycin 
                 Nystatin 
                 Azacitidine 
               
               
                 Trihexyphenidyl 
                 ONO 2235 
                 Aspirin 
               
               
                 Busulfan 
                 Nocodazole 
                 Amlodipine 
               
               
                 Nimodipine 
                 1-Methyl-3-isobutylxanthine 
                 dasatinib 
               
               
                 Nortriptyline 
                 Losartan 
                 Verapamil 
               
               
                 Mebendazole  
                 Loratadine 
                 Baclofen 
               
               
                 Piroxicam 
                 Ionomycin 
                 Zalcitabine 
               
               
                 Flunarizine 
                 Guanethidine 
                 Deoxyglucose 
               
               
                 Levodopa 
                 8-((4-chlorophenyl)thio)cyclic-3′,5′-AMP 
                 triptolide 
               
               
                 Lorazepam 
                 Sarin 
                 Cyclophosphamide 
               
               
                 Chlorambucil 
                 Methyl Methanesulfonate 
                 Ascorbic Acid 
               
            
           
           
               
            
               
                 A2. Molecules that downregulate PRODH: 
               
            
           
           
               
               
               
            
               
                 Aminosalicylic Acid 
                 Ursodeoxycholic Acid 
                 Miconazole 
               
               
                 anastrozole 
                 Clotrimazole 
                 Nafenopin 
               
               
                 Thioacetamide 
                 Tinidazole 
                 Salicylates 
               
               
                 Spironolactone 
                 rabeprazole 
                 Hexachlorobenzene 
               
               
                 Carbon Tetrachloride 
                 bromfenac 
                 Fenofibrate 
               
               
                 Lovastatin 
                 Praziquantel 
                 Bezafibrate 
               
               
                 pirinixic acid 
                 Methapyrilene 
                 Ethylestrenol 
               
               
                 Fluconazole 
                 Theobromine 
                 Indomethacin 
               
               
                 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 
                 Isoniazid 
                 Dipyrone 
               
               
                 9,10-oxide 
                   
                   
               
               
                 celecoxib 
                 Stavudine 
                 geraniol 
               
               
                 Dimethylnitrosamine 
                 Ketorolac 
                 Simvastatin 
               
               
                 Aminoglutethimide 
                 pantoprazole 
                 ferulic acid 
               
               
                 Cyproterone Acetate 
                 Stanozolol 
                 Econazole 
               
               
                 N-nitrosomorpholine 
                 vinylidene chloride 
                 Chloroform 
               
               
                 Diethylstilbestrol 
                 Ecdysterone 
                 Mestranol 
               
               
                 Benzbromarone 
                 naftopidil 
                 beta-Naphthoflavone 
               
               
                 temafloxacin 
                 atorvastatin 
                 Ticlopidine 
               
               
                 Aphidicolin 
                 Ticrynafen 
                 Piperonyl Butoxide 
               
               
                 rosiglitazone 
                 TO-901317 
                 Estriol 
               
               
                 Proglumide 
                 Cyproterone 
                 Ibuprofen 
               
               
                 bromobenzene 
                 artemisinine 
                 Ethinyl Estradiol 
               
               
                 Chlormezanone 
                 Gemfibrozil 
                 Ajmaline 
               
               
                 benziodarone 
                 Diethylhexyl Phthalate 
                 Diethylnitrosamine 
               
               
                 Clonazepam 
                 Clofibrate 
                 beta-cyclodextrin-benzaldehyde 
               
               
                 Pravastatin 
                 Chloramphenicol 
                 Phenobarbital 
               
               
                 tranilast 
                 Dehydroepiandrosterone 
                 piclamilast 
               
               
                 Bupropion 
                 Pentobarbital 
                 Fendiline 
               
               
                 cetraxate 
                 terbinafine 
                 Danazol 
               
               
                 Clonidine 
                 Vinblastine 
                 Ethylnitrosourea 
               
               
                 carvedilol 
                 pioglitazone 
                 abacavir 
               
               
                 Clofibric Acid 
                 Cefixime 
                 Shiga Toxin 
               
               
                 Disulfiram 
                 2-Acetylaminofluorene 
                 Carisoprodol 
               
               
                 ipriflavone 
                 Spectinomycin 
                 irbesartan 
               
               
                 perfluorooctanoic acid 
                 Flutamide 
                 methylformamide 
               
               
                 lornoxicam 
                 Mifepristone 
                 bendazolic acid 
               
               
                 ciprofibrate 
                 Finasteride 
                 Neostigmine 
               
               
                 Methylcholanthrene 
                 nimesulide 
                 zileuton 
               
               
                 Vitamin K 3 
                 2-nitrofluorene 
                 Metronidazole 
               
               
                 amitraz 
                 closantel 
                 4-nonylphenol 
               
               
                 Oxytetracycline 
                 penciclovir 
                 Secobarbital 
               
               
                 Cinnarizine 
                 Ethambutol 
                 Colchicine 
               
               
                 salicylamide 
                 zopiclone 
                 desloratadine 
               
               
                 Methyltestosterone 
                 Tetrachlorodibenzodioxin 
                 Granisetron 
               
               
                 Safrole 
                 trovafloxacin 
                 2-dichlorobenzene 
               
               
                 Doxepin 
                 Gonadotropins 
                 eperisone 
               
               
                 Carbamazepine 
                 Roflumilast 
                 N-methylolacrylamide 
               
               
                 Azathioprine 
                 hydrazine 
                 Parathion 
               
               
                 Ondansetron 
                 Monocrotaline 
                 Pyrogallol 
               
               
                 Estradiol  
                 balsalazide 
                 Carmustine 
               
               
                 phenothiazine 
                 sparfloxacin 
                 triadimefon 
               
               
                 Clofazimine 
                 1-hydroxycholecalciferol 
                 pristane 
               
               
                 bortezomib 
                 Mefloquine 
                 Fonofos 
               
               
                 Clomipramine 
                 Tretinoin 
                 systhane 
               
               
                 coumarin 
                 amineptin 
                 naphthalenediimide 
               
               
                 Acetaminophen 
                 Enoxacin 
                 Omeprazole 
               
               
                 telmisartan 
                 4-(5-benzo(1,3)dioxol-5-yl- 
                   
               
               
                   
                 4-pyridin-2-yl-1H-imidazol-2-yl)benzamide 
                 Zimeldine 
               
               
                 Isoproterenol 
                 Benzalkonium Compounds 
                 Dimercaprol 
               
               
                 Bicuculline 
                 tenofovir 
                 tenidap 
               
               
                 hydroxytamoxifen 
                 norethindrone acetate 
                 sulfathiazole 
               
               
                 Erythromycin 
                 Tolazamide 
                 Galantamine 
               
               
                 Minoxidil 
                 Sertraline 
                 Trimethadione 
               
               
                 Dactinomycin 
                 perfluorooctane sulfonic acid 
                 Ethionine 
               
               
                 Progesterone 
                 Vanadates 
                 venlafaxine 
               
               
                 Tetracycline 
                 rofecoxib 
                 graveoline 
               
               
                 tazobactam 
                 lactacystin 
                 Glycerol 
               
               
                 Amitriptyline 
                 Diclofenac 
                 Griseofulvin 
               
               
                 Naloxone 
                 Caerulein 
                 benoxaprofen 
               
               
                 urapidil 
                 Benzethonium 
                 Megestrol 
               
               
                 Floxuridine 
                 quintozene 
                 shikonin 
               
               
                 Buthionine Sulfoximine 
                 Prednisone 
                 Lamivudine 
               
               
                 Propylthiouracil 
                 ranolazine 
                 Protoveratrines 
               
               
                 oxfendazole 
                 Cefotetan 
                 Aflatoxin B1 
               
               
                 Amantadine 
                 Capsaicin 
                 Megestrol Acetate 
               
               
                 Todralazine 
                 Amiodarone 
                 ibufenac 
               
               
                 sunitinib 
                 Nifedipine 
                 Norethindrone 
               
               
                 meropenem 
                 1,10-phenanthroline 
                 Ethionamide 
               
               
                 Phenylephrine  
                 compactin 
                 Lasalocid 
               
               
                 oxalylglycine 
                 esmolol 
                 lansoprazole 
               
               
                 homatropine 
                 Penicillamine 
                 Lead 
               
               
                 Nitroprusside 
                 bambuterol 
                 Bleomycin 
               
               
                 Diphenhydramine 
                 etofylline 
                 Benzo(a)pyrene 
               
               
                 Lomustine 
                 methylparaben 
                 Ouabain 
               
               
                 etiracetam 
                 idebenone 
                 cilostazol 
               
               
                 ochratoxin A 
                 isoconazole 
                 guanadrel 
               
               
                 Nickel 
                 1-ethyl-2-benzimidazolinone 
                 Rifampin 
               
               
                 Raloxifene 
                 Thiabendazole 
                 Benzydamine 
               
               
                 indole-3-carbinol 
                 Hydroxyzine 
                 Astemizole 
               
               
                 Diazepam 
                 Vitamin B 12 
                 Chitosan 
               
               
                 Nisoldipine 
                 Alprazolam 
                 Aconitine 
               
               
                 4-hydroxytamoxifen 
                 Oxazepam 
                 Bacitracin 
               
               
                 Dipyridamole 
                 Citalopram 
                 Atropine 
               
               
                 efavirenz 
                 Sotalol 
                 Genistein 
               
               
                 dironyl 
                 Soman 
                 U 0126 
               
               
                 deferiprone 
                 pralidoxime 
                 Propranolol 
               
               
                 Camptothecin 
                 Tolazoline 
                 HI 6 
               
               
                 resveratrol 
                 Cytarabine 
                 Allopurinol 
               
               
                 Quercetin 
                 Clozapine 
                 sildenafil 
               
               
                 Labetalol 
                 Albendazole 
                 valsartan 
               
               
                 Famotidine 
                 Ciprofloxacin 
                 Gentamicins 
               
               
                 Tacrine 
                 Amphetamine 
                 Nadolol 
               
               
                 Chlorpheniramine 
                 Mitomycin 
                 MRK 003 
               
               
                 Netilmicin 
                 Paroxetine 
                 Pregnenolone Carbonitrile 
               
               
                 6-bromoindirubin-3′-oxime 
                 doxofylline 
                 Azauridine 
               
               
                 Paclitaxel 
                 benzyloxycarbonylleucyl- 
                 NG-Nitroarginine Methyl 
               
               
                   
                 leucyl-leucine aldehyde 
                 Ester 
               
               
                 N,N′-diphenyl-4-  
                 Calcitriol 
                 Enalapril 
               
               
                 phenylenediamine 
                   
                   
               
               
                 SB 203580 
                 bisphenol A 
                 Inosine Monophosphate 
               
               
                 Perhexiline 
                 cyanoginosin LR 
                 gemcitabine 
               
               
                 Kainic Acid 
                 Pentylenetetrazole 
                 6-Mercaptopurine 
               
               
                 Promethazine 
                   
                   
               
            
           
           
               
            
               
                 B1. Molecules that upregulate COMT: 
               
            
           
           
               
               
               
            
               
                 Sulbactam 
                 6-methoxy-2-naphthylacetic acid 
                 Cefuroxime 
               
               
                 Diazoxide 
                 Stanozolol 
                 Lead 
               
               
                 2,4-Dinitrophenol 
                 tenidap 
                 Norfloxacin 
               
               
                 Cephalexin 
                 rosiglitazone 
                 pirinixic acid 
               
               
                 Vanadates 
                 Levobunolol 
                 lorglumide 
               
               
                 Metoprolol 
                 Trimetazidine 
                 oltipraz 
               
               
                 Omeprazole 
                 Methylcholanthrene 
                 Quinpirole 
               
               
                 chloroxylenol 
                 Pyridoxine 
                 tropisetron 
               
               
                 Noscapine 
                 Inosine Monophosphate 
                 Nitroprusside 
               
               
                 beta-Naphthoflavone 
                 Clomipramine 
                 Netilmicin 
               
               
                 Fluphenazine 
                 Itraconazole 
                 bromodichloromethane 
               
               
                 4-dichlorobenzene 
                 Benserazide 
                 nabumetone 
               
               
                 apramycin 
                 Altretamine 
                 butenafine 
               
               
                 tomatidine 
                 Econazole 
                 Pemoline 
               
               
                 NG-Nitroarginine Methyl Ester 
                 Epirubicin 
                 tazobactam 
               
               
                 Diethylnitrosamine 
                 etofenamate 
                 Mitoxantrone 
               
               
                 graveoline 
                 betulinic acid 
                 arsenic trioxide 
               
               
                 Cortisone 
                 Sotalol 
                 Promethazine 
               
               
                 temsirolimus  
                 Dimethylformamide 
                 Progesterone 
               
               
                 sulfathiazole 
                 beta-cyclodextrin-benzaldehyde 
                 Galantamine 
               
               
                 oxaliplatin 
                 Trichloroethylene 
                 vinorelbine 
               
               
                 pentachlorobenzene 
                 riddelliine 
                 Ethacrynic Acid 
               
               
                 Neomycin 
                 Ethionine 
                 valsartan 
               
               
                 gefitinib 
                 Terazosin 
                 Mifepristone 
               
               
                 Acarbose 
                 bestatin 
                 1-Methyl-4-phenyl-1,2,3,6- 
               
               
                   
                   
                 tetrahydropyridine 
               
               
                 Iproniazid 
                 3,3′,4′,5 tetrachlorosalicylanilide 
                 Warfarin 
               
               
                 Benzethonium 
                 Chloroquine 
                 Citalopram 
               
               
                 Vitamin K 2 
                 gabapentin 
                 Sulindac 
               
               
                 Roxithromycin 
                 oxfendazole 
                 letrozole 
               
               
                 Chitosan 
                 N-Methyl-3,4- 
                 Azithromycin 
               
               
                   
                 methylenedioxyamphetamine 
                   
               
               
                 Clindamycin 
                 Cytochalasin B 
                 Sulfinpyrazone 
               
               
                 pristane 
                 Simazine 
                 Cholecalciferol 
               
               
                 Doxapram 
                 erlotinib 
                 Tetracycline 
               
               
                 marimastat 
                 Atropine 
                 fenbufen 
               
               
                 Tetrachlorodibenzodioxin 
                 Flunarizine 
                 Niacin 
               
               
                 PK 11195 
                 Polychlorinated Biphenyls 
                 Clonidine 
               
               
                 homosalate 
                 spiradoline 
                 Phentolamine 
               
               
                 Ethamsylate 
                 Scopolamine Hydrobromide 
                 Chlorambucil 
               
               
                 1,1,1-trichloroethane 
                 asperflavin 
                 zomepirac 
               
               
                 Selenomethionine 
                 N-(2-aminophenyl)-4-(N-(pyridin-3- 
                 Benzo(a)pyrene 
               
               
                   
                 ylmethoxycarbonyl)aminomethyl)benzamide 
                   
               
               
                 clebopride  
                 Concanavalin A 
                 Lovastatin 
               
               
                 mebeverine 
                 Doxorubicin 
                 Lorazepam 
               
               
                 Simvastatin 
                 6-bromoindirubin-3′-oxime 
                 sorafenib 
               
               
                 rofecoxib 
                 U 0126 
                 celecoxib 
               
               
                 SU 5402 
                 sildenafil 
                 imatinib 
               
               
                 anastrozole 
                 2-(4-morpholinyl)-8-phenyl- 
                 adiphenine 
               
               
                   
                 4H-1-benzopyran-4-one 
                   
               
               
                 methantheline 
                 clemizole 
                 olanzapine 
               
               
                 fluvastatin 
                 chelidonine 
                 lansoprazole 
               
               
                 ebastine 
                 cyanoginosin LR 
                 clopidogrel 
               
               
                 bromfenac 
                 alfuzosin 
                 carvedilol 
               
               
                 dihydroquinghaosu 
                 idebenone 
                 vitexin 
               
               
                 fragment C, human serum albumin 
                 closantel 
                 cobaltous chloride 
               
               
                 bromopride 
                 ceforanide 
                 ascorbate-2-phosphate 
               
               
                 ciclopirox 
                 2,4-diaminotoluene 
                 9-(2-hydroxy-3-nonyl)adenine 
               
               
                 cineole 
                 tolfenamic acid 
                 6-thioguanosine 
               
               
                 hexylcaine 
                 pimethixene 
                 5-fluorouridine 
               
               
                 triptolide 
                 Cardiotoxins 
                 Dichlororibofuranosylbenzimidazole 
               
               
                 Antibodies, Monoclonal 
                 Caerulein 
                 Ionomycin 
               
               
                 Streptomycin 
                 Bleomycin 
                 Chorionic Gonadotropin 
               
               
                 Beclomethasone 
                 Cyproterone Acetate 
                 Chlormadinone Acetate 
               
               
                 Finasteride 
                 Colistin 
                 Alpha-Amanitin 
               
               
                 Rifampin 
                 Amoxapine 
                 Mianserin 
               
               
                 Clozapine 
                 Dactinomycin 
                 Enoxacin 
               
               
                 Ciprofloxacin 
                 1-Methyl-3-isobutylxanthine 
                 Acyclovir 
               
               
                 8-Bromo Cyclic Adenosine Monophosphate 
                 Allopurinol 
                 Melatonin 
               
               
                 Cytochalasin D 
                 gamma-Tocopherol 
                 alpha-Tocopherol 
               
               
                 Vitamin E  
                 Acenocoumarol 
                 Astemizole 
               
               
                 Diltiazem 
                 Nitrazepam 
                 Diazepam 
               
               
                 Apazone 
                 Cotinine 
                 Kainic Acid 
               
               
                 Fluorouracil 
                 Risperidone 
                 Zidovudine 
               
               
                 Stavudine 
                 Cytarabine 
                 Chlorpheniramine 
               
               
                 Nevirapine 
                 Nicardipine 
                 Trazodone 
               
               
                 Amiodarone 
                 Fluconazole 
                 Clotrimazole 
               
               
                 Nicotine 
                 Pilocarpine 
                 Lobeline 
               
               
                 Reserpine 
                 Vinblastine 
                 Quinidine 
               
               
                 Papaverine 
                 Apomorphine 
                 Dacarbazine 
               
               
                 Acetazolamide 
                 Thiethylperazine 
                 Bithionol 
               
               
                 Isoflurophate 
                 Auranofin 
                 Ethylnitrosourea 
               
               
                 Dimethylnitrosamine 
                 Erythromycin 
                 Haloperidol 
               
               
                 Ifosfamide 
                 Cyclophosphamide 
                 Chloroform 
               
               
                 7,8-Dihydro-7,8- 
                 Naproxen 
                 Demeclocycline 
               
               
                 dihydroxybenzo(a)pyrene 
                   
                   
               
               
                 9,10-oxide 
                   
                   
               
               
                 Loratadine 
                 Amitriptyline 
                 Losartan 
               
               
                 Ketamine 
                 Isoniazid 
                 Ketoprofen 
               
               
                 Ibuprofen 
                 Fenoprofen 
                 Diflunisal 
               
               
                 Mefenamic Acid 
                 Diethylcarbamazine 
                 Aminocaproic Acids 
               
               
                 Gemfibrozil 
                 Clofibric Acid 
                 Azoxymethane 
               
               
                 Azauridine 
                 Methapyrilene 
                 Dobutamine 
               
               
                 Amrinone 
                 Guanethidine 
                 Amoxicillin 
               
               
                 Cefotaxime 
                 Dibucaine 
                 Sulpiride 
               
               
                 Busulfan 
                 Isoxsuprine 
                 Bismuth 
               
               
                 Calcium 
                   
                   
               
            
           
           
               
            
               
                 B2. Molecules that down regulate COMT: 
               
            
           
           
               
               
               
            
               
                 Tin Fluorides  
                 Tobramycin 
                 Phenacetin 
               
               
                 dexibuprofen 
                 bendazolic acid 
                 3-hydroxyacetanilide 
               
               
                 Cyclosporine 
                 flubendazole 
                 Acrolein 
               
               
                 cephalonium 
                 Fluoxetine 
                 valdecoxib 
               
               
                 Hesperidin 
                 nimetazepam 
                 Niacinamide 
               
               
                 Diethylstilbestrol 
                 ajmalicine 
                 Trichlorfon 
               
               
                 2-nitrofluorene 
                 clinafloxacin 
                 Ethinyl Estradiol 
               
               
                 methiazole 
                 Gentamicins 
                 Cyproheptadine 
               
               
                 Chlorpropamide 
                 Iornoxicam 
                 Bezafibrate 
               
               
                 Methoxsalen 
                 4-hydroxyestradiol-17 beta 
                 Suprofen 
               
               
                 Piperonyl Butoxide 
                 norethindrone acetate 
                 Clomiphene 
               
               
                 Nizatidine 
                 4-acetylaminofluorene 
                 DDT 
               
               
                 Meptazinol 
                 Trioxsalen 
                 Carmustine 
               
               
                 acidocin CH5,  Lactobacillus   
                 Cymarine 
                 Acetylmuramyl-Alanyl- 
               
               
                 
                   acidophilus 
                 
                   
                 Isoglutamine 
               
               
                 Tiletamine 
                 atorvastatin 
                 salicylamide 
               
               
                 cilostazol 
                 vinylidene chloride 
                 ferulic acid 
               
               
                 Cyclizine 
                 ifenprodil 
                 hydroquinone 
               
               
                 Dyphylline 
                 Procarbazine 
                 Ampicillin 
               
               
                 Estriol 
                 Propylthiouracil 
                 Fursultiamin 
               
               
                 Cloxacillin 
                 fipronil 
                 Theophylline 
               
               
                 apicidin 
                 Coumaphos 
                 ONO 2235 
               
               
                 meloxicam 
                 lomefloxacin 
                 phosphonoacetamide 
               
               
                 oxiconazole 
                 fulvestrant 
                 Podophyllotoxin 
               
               
                 Acetaminophen 
                 cinchonine 
                 Aspirin 
               
               
                 Atractyloside 
                 penciclovir 
                 Cinnarizine 
               
               
                 Terfenadine 
                 Ketorolac 
                 Raloxifene 
               
               
                 trichostatin A 
                 Tretinoin 
                 Natamycin 
               
               
                 Mestranol 
                 Estradiol 
                 Nystatin 
               
               
                 2-chloropyrazine 
                 Azathioprine 
                 Flufenamic Acid 
               
               
                 picrotoxinin  
                 Aminosalicylic Acid 
                 asiaticoside 
               
               
                 daidzein 
                 Tiapamil Hydrochloride 
                 Valproic Acid 
               
               
                 Diquat 
                 Carboplatin 
                 Tacrolimus 
               
               
                 ranolazine 
                 piperacetazine 
                 Curcumin 
               
               
                 pramoxine 
                 Idoxuridine 
                 Ethylestrenol 
               
               
                 Todralazine 
                 boldine 
                 sparfloxacin 
               
               
                 Cetylpyridinium 
                 Nafenopin 
                 abamectin 
               
               
                 Canrenoate Potassium 
                 Dantrolene 
                 Cisapride 
               
               
                 bisphenol A 
                 Dihydroergocristine 
                 Calcitriol 
               
               
                 decitabine 
                 Diethylhexyl Phthalate 
                 Budesonide 
               
               
                 2-dichlorobenzene 
                 Okadaic Acid 
                 eperisone 
               
               
                 Carbimazole 
                 Genistein 
                 Hymecromone 
               
               
                 biphenylylacetic acid 
                 Ampyrone 
                 canadine 
               
               
                 U 54494A 
                 syrosingopine 
                 tetrahydrotriamcinolone 
               
               
                 blebbistatin 
                 phenacemide 
                 Hydralazine 
               
               
                 Propranolol 
                 Oxazepam 
                 terbinafine 
               
               
                 Pyrantel 
                 Leucovorin 
                 Mustard Gas 
               
               
                 nimesulide 
                 Acetohexamide 
                 Propanil 
               
               
                 pioglitazone 
                 benfluorex 
                 Pregnenolone 
               
               
                 1,2-dithiol-3-thione 
                 Dinoprostone 
                 Phenobarbital 
               
               
                 Thioctic Acid 
                 Propantheline 
                 Protriptyline 
               
               
                 Clofibrate 
                 Cytokines 
                 bis(tri-n-butyltin)oxide 
               
               
                 Sulfaphenazole 
                 Piribedil 
                 hydrazine 
               
               
                 Aztreonam 
                 tosufloxacin 
                 Oxymetazoline 
               
               
                 4-biphenylamine 
                 Lomustine 
                 1-hydroxycholecalciferol 
               
               
                 ubiquinol 
                 Doxylamine 
                 Levamisole 
               
               
                 scriptaid 
                 phenylhydrazine 
                 hydroxyhydroquinone 
               
               
                 Betamethasone 
                 Pheniramine 
                 Tolnaftate 
               
               
                 4-(5-benzo(1,3)dioxol-5-yl-4- 
                 direct black 3 
                 Dipyridamole 
               
               
                 pyridin-2-yl-1H-imidazol-2-yl)benzamide 
                   
                   
               
               
                 repaglinide  
                 naphthalenediimide 
                 rimexolone 
               
               
                 Thiostrepton 
                 Sulfamethazine 
                 Timolol 
               
               
                 Tacrine 
                 acetovanillone 
                 Trichloroepoxypropane 
               
               
                 eticlopride 
                 8-aminohexylamino cAMP 
                 Streptozocin 
               
               
                 HC toxin 
                 vorinostat 
                 genipin 
               
               
                 dibenzazepine 
                 4-methyl-N-(3-(4-methylimidazol-1-yl)-5- 
                 LBH589 
               
               
                   
                 (trifluoromethyl)phenyl)-3-((4-pyridin-3- 
                   
               
               
                   
                 ylpyrimidin-2-yl)amino)benzamide 
                   
               
               
                 lapatinib 
                 dasatinib 
                 bevacizumab 
               
               
                 CPG-oligonucleotide 
                 bortezomib 
                 17-(allylamino)-17- 
               
               
                   
                   
                 demethoxygeldanamycin 
               
               
                 Y 27632 
                 1-ethyl-2-benzimidazolinone 
                 azacyclonol 
               
               
                 tenofovir 
                 benzyloxycarbonylvalyl-alanyl-aspartyl 
                 bexarotene 
               
               
                   
                 fluoromethyl ketone 
                   
               
               
                 daboiatoxin 
                 piclamilast 
                 cerivastatin 
               
               
                 telmisartan 
                 irbesartan 
                 colforsin 
               
               
                 benzyloxycarbonylleucyl- 
                 zardaverine 
                 zileuton 
               
               
                 leucyl-leucine aldehyde 
                   
                   
               
               
                 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline 
                 dorzolamide 
                 resveratrol 
               
               
                 1,2-dilinolenoyl-3-(4- 
                 gemcitabine 
                 aceclofenac 
               
               
                 aminobutyryl)propane-1,2,3-triol 
                   
                   
               
               
                 levocabastine 
                 buparvaquone 
                 leflunomide 
               
               
                 vanoxerine 
                 1,3-dichlorobenzene 
                 oxalylglycine 
               
               
                 monorden 
                 ozagrel 
                 artemether 
               
               
                 lysophosphatidic acid 
                 bromobenzene 
                 beta-glycerophosphoric acid 
               
               
                 artemisinine 
                 doxofylline 
                 sulmazole 
               
               
                 dexamisole 
                 ochratoxin A 
                 perfluorooctanoic acid 
               
               
                 2-methoxyestradiol  
                 4-O-methyl-12-O-tetradecanoylphorbol 13- 
                 ciprofibrate 
               
               
                   
                 acetate 
                   
               
               
                 sodium arsenite 
                 4-hydroxytamoxifen 
                 8-((4- 
               
               
                   
                   
                 chlorophenyl)thio)cyclic-3′,5′-AMP 
               
               
                 lycorine 
                 dipivefrin 
                 amitraz 
               
               
                 tranilast 
                 compactin 
                 benoxaprofen 
               
               
                 acadesine 
                 halofuginone 
                 diphenylpyraline 
               
               
                 wortmannin 
                 4,4′-diaminodiphenylmethane 
                 alginic acid 
               
               
                 naringin 
                 isoascorbic acid 
                 benzothiazide 
               
               
                 geldanamycin 
                 Shiga Toxin 
                 Cholera Toxin 
               
               
                 BCG Vaccine 
                 Ribavirin 
                 Phytohemagglutinins 
               
               
                 Antigen-Antibody Complex 
                 Enalapril 
                 Captopril 
               
               
                 Phenylalanine 
                 Palmitic Acid 
                 Alprostadil 
               
               
                 Deoxyglucose 
                 Clobetasol 
                 Dexamethasone 
               
               
                 Danazol 
                 Vecuronium Bromide 
                 Dihydrotestosterone 
               
               
                 Androsterone 
                 Viomycin 
                 Bacitracin 
               
               
                 Clofazimine 
                 Carbamazepine 
                 Quinacrine 
               
               
                 Oxolinic Acid 
                 Clioquinol 
                 Oxyquinoline 
               
               
                 Amodiaquine 
                 Thioguanine 
                 Bucladesine 
               
               
                 Vidarabine 
                 Methotrexate 
                 Saquinavir 
               
               
                 Indomethacin 
                 Dicumarol 
                 Rotenone 
               
               
                 Quercetin 
                 Luteolin 
                 Aflatoxin B1 
               
               
                 Nocodazole 
                 Atrazine 
                 Rolipram 
               
               
                 Clemastine 
                 Triprolidine 
                 2,2′-Dipyridyl 
               
               
                 Nifedipine 
                 Trihexyphenidyl 
                 Aminoglutethimide 
               
               
                 Cycloheximide 
                 Paroxetine 
                 Domperidone 
               
               
                 Ketoconazole 
                 Betazole 
                 Miconazole 
               
               
                 Pentylenetetrazole 
                 Caffeine 
                 Dextromethorphan 
               
               
                 Vincristine 
                 Ajmaline 
                 Harmaline 
               
               
                 Dihydroergotamine 
                 Pergolide 
                 Colchicine 
               
               
                 Cam ptothecin 
                 Fusaric Acid 
                 Hydroxyurea 
               
               
                 Allantoin 
                 Dimethyl Sulfoxide 
                 Hydrochlorothiazide 
               
               
                 6-Mercaptopurine 
                 Triflupromazine 
                 Thioridazine 
               
               
                 Promazine 
                 Perphenazine 
                 Mesoridazine 
               
               
                 Chlorpromazine 
                 Acetylcysteine 
                 Mitomycin 
               
               
                 Diazinon 
                 Dichlorvos 
                 Pregnenolone Carbonitrile 
               
               
                 Clarithromycin 
                 Brefeldin A 
                 Melphalan 
               
               
                 Carbon Tetrachloride 
                 Pravastatin 
                 Vitamin K 3 
               
               
                 Plicamycin 
                 Daunorubicin 
                 Aclarubicin 
               
               
                 Meclizine 
                 Thapsigargin 
                 Paclitaxel 
               
               
                 Amantadine 
                 Methyl Methanesulfonate 
                 Phenelzine 
               
               
                 Doxepin 
                 Diclofenac 
                 Dicyclomine 
               
               
                 Puromycin 
                 Ascorbic Acid 
                 Dextropropoxyphene 
               
               
                 Disulfiram 
                 Mycophenolic Acid 
                 Butyric Acid 
               
               
                 Vigabatrin 
                 Baclofen 
                 Azacitidine 
               
               
                 Ipratropium 
                 Granisetron 
                 Edrophonium 
               
               
                 Gallamine Triethiodide 
                 Benzalkonium Compounds 
                 Aminophylline 
               
               
                 Fluvoxamine 
                 Verapamil 
                 Mephentermine 
               
               
                 Methamphetamine 
                 Amphetamine 
                 Methyldopa 
               
               
                 Levodopa 
                 Bromhexine 
                 Furosemide 
               
               
                 Ceftazidime 
                 Cephaloridine 
                 Cephalothin 
               
               
                 Cefazolin 
                 2-Acetylaminofluorene 
                 Nadolol 
               
               
                 Metaproterenol 
                 Midodrine 
                 Isoproterenol 
               
               
                 Epinephrine 
                 Clenbuterol 
                 Choline 
               
               
                 Cisplatin 
                 Lithium Carbonate 
                   
               
            
           
           
               
            
               
                 C1. Molecules that upregulate PYCR1: 
               
            
           
           
               
               
               
            
               
                 Ethionamide 
                 halofuginone 
                 coumarin 
               
               
                 Asbestos 
                 Hyaluronic Acid 
                 methylformamide 
               
               
                 Teriparatide 
                 Phenylephrine 
                 Carbon Tetrachloride 
               
               
                 Mannitol 
                 Ethambutol 
                 1,3-dichloro-2-propanol 
               
               
                 artemisinine 
                 clebopride 
                 4-(4-fluorophenyl)-2-(4- 
               
               
                   
                   
                 hydroxyphenyl)-5-(4- 
               
               
                   
                   
                 pyridyl)imidazole 
               
               
                 Methimazole 
                 Hypericum extract LI 160 
                 Carbimazole 
               
               
                 Riluzole 
                 bromobenzene 
                 6-bromoindirubin-3′-oxime 
               
               
                 Methapyrilene 
                 Chlormezanone 
                 U 0126 
               
               
                 Trimethadione 
                 Chloroform 
                 Tunicamycin 
               
               
                 Nafcillin 
                 Cloxacillin 
                 hydrazine 
               
               
                 crotamiton 
                 Ticlopidine 
                 Procyclidine 
               
               
                 ceforanide 
                 estradiol 3-benzoate 
                 4-methyl-N-(3-(4- 
               
               
                   
                   
                 methylimidazol-1-yl)-5- 
               
               
                   
                   
                 (trifluoromethyl)phenyl)- 
               
               
                   
                   
                 3-((4-pyridin-3-ylpyrimidin-2- 
               
               
                   
                   
                 yl)amino)benzamide 
               
               
                 Okadaic Acid 
                 ascorbate-2-phosphate 
                 GW 3965 
               
               
                 Azoxymethane 
                 Estriol 
                 Propylthiouracil 
               
               
                 Trenbolone Acetate, (17beta)-isomer 
                 4-dichlorobenzene 
                 Estradiol 
               
               
                 Cymarine 
                 3-nitropropionic acid 
                 Molindone 
               
               
                 Tryptophan  
                 Trichlormethiazide 
                 Propoxycaine 
               
               
                 graveoline 
                 Glycocholic Acid 
                 Mestranol 
               
               
                 4,5-dianilinophthalimide 
                 N-(2-aminophenyl)-4-(N-(pyridin-3- 
                 Thioctic Acid 
               
               
                   
                 ylmethoxycarbonyl)aminomethyl)benzamide 
                   
               
               
                 Thiabendazole 
                 Insulin 
                 Clodronic Acid 
               
               
                 2-dichlorobenzene 
                 Disulfiram 
                 Cephapirin 
               
               
                 Doxycycline 
                 Carbamazepine 
                 anastrozole 
               
               
                 Acetaminophen 
                 Cephalexin 
                 Cyproterone Acetate 
               
               
                 shogaol 
                 Stavudine 
                 2,4-Dinitrophenol 
               
               
                 Dihydrotestosterone 
                 Carcinogens 
                 Bromocriptine 
               
               
                 iodoform 
                 Thapsigargin 
                 Danazol 
               
               
                 Dimethylformamide 
                 arcaine 
                 vanoxerine 
               
               
                 fosfosal 
                 Thioacetamide 
                 Canavanine 
               
               
                 Piromidic Acid 
                 pantoprazole 
                 KCB-1 protein, recombinant 
               
               
                 epidermal growth factor (1-45) 
                 oltipraz 
                 Omeprazole 
               
               
                 diisopropyl methylphosphonate 
                 Hydrogen Peroxide 
                 Clonazepam 
               
               
                 acetylleucine 
                 Reserpine 
                 Dapsone 
               
               
                 Fluconazole 
                 Ethinyl Estradiol 
                 Sulfadimethoxine 
               
               
                 Nalidixic Acid 
                 Estrogens 
                 Azacitidine 
               
               
                 etofenamate 
                 Erythromycin 
                 Sulindac 
               
               
                 epoxomicin 
                 sulconazole 
                 Methylene Chloride 
               
               
                 Pipemidic Acid 
                 Cefazolin 
                 Bleomycin 
               
               
                 Trimipramine 
                 Ultraviolet Rays 
                 tolfenamic acid 
               
               
                 Spiperone 
                 Todralazine 
                 Phenobarbital 
               
               
                 Allopurinol 
                 Isoniazid 
                 1,2-dithiol-3-thione 
               
               
                 oxaliplatin 
                 Equilin 
                 Orphenadrine 
               
               
                 Amphotericin B 
                 N-(2-cyclohexyloxy-4- 
                 zaprinast 
               
               
                   
                 nitrophenyl)methanesulfonamide 
                   
               
               
                 apicidin 
                 BCG Vaccine 
                 closantel 
               
               
                 Roxithromycin 
                 kavain 
                 dironyl 
               
               
                 tracazolate  
                 Methyltestosterone 
                 Ionomycin 
               
               
                 Amanitins 
                 Lasalocid 
                 withaferin A 
               
               
                 Pentolinium Tartrate 
                 pristane 
                 Hexachlorobenzene 
               
               
                 oxolamine 
                 Hydroflumethiazide 
                 Hydroxyzine 
               
               
                 Stanozolol 
                 sodium nitrate 
                 Triflupromazine 
               
               
                 Oxyquinoline 
                 Roflumilast 
                 Thiethylperazine 
               
               
                 Gossypol 
                 phenothiazine 
                 Fursultiam in 
               
               
                 Muromonab-CD3 
                 Ibuprofen 
                 Trimethoprim 
               
               
                 cerivastatin 
                 N-benzyladenine 
                 Tetrachlorodibenzodioxin 
               
               
                 X-Rays 
                 Diazepam 
                 Phenazopyridine 
               
               
                 Cyproheptadine 
                 Selegiline 
                 salmeterol 
               
               
                 bromperidol 
                 Clioquinol 
                 Pizotyline 
               
               
                 Ketorolac 
                 acetorphan 
                 Cefaclor 
               
               
                 verteporfin 
                 Phenelzine 
                 Khellin 
               
               
                 (melle-4)cyclosporin 
                 Nifedipine 
                 Isoproterenol 
               
               
                 Diethylstilbestrol 
                 Vitamin E 
                 Diquat 
               
               
                 Prenylamine 
                 Deoxyglucose 
                 gibberellic acid 
               
               
                 Cinnarizine 
                 Azathioprine 
                 Acetazolamide 
               
               
                 Carmustine 
                 butoconazole 
                 Diclofenac 
               
               
                 Domperidone  
                 abamectin 
                 Benzocaine 
               
               
                 famprofazone 
                 Particulate Matter 
                 Progesterone 
               
               
                 Gentamicins 
                 Desoxycorticosterone 
                 Monensin 
               
               
                 Remoxipride 
                 sodium arsenite 
                 Benzethonium 
               
               
                 Genistein 
                 hydrastinine 
                 Phenylalanine 
               
               
                 Felodipine 
                 Glycerol 
                 Captopril 
               
               
                 fulvestrant 
                 Acetohexamide 
                 nifuroxazide 
               
               
                 hydroxyachillin 
                 Tobramycin 
                 bisphenol A 
               
               
                 Astemizole 
                 rituximab 
                 Folic Acid 
               
               
                 methylbenzethonium 
                 enterotoxin B, staphylococcal 
                 Hydrogel 
               
               
                 Cyclosporine 
                 Caerulein 
                 Mesalamine 
               
               
                 Naproxen 
                 bicalutamide 
                 fragment C, human serum albumin 
               
               
                 tibolone 
                 Antibodies, Monoclonal 
                 LBH589 
               
               
                 phorbolol myristate acetate 
                 Soman 
                 Niclosamide 
               
               
                 Tiapamil Hydrochloride 
                 Clotrimazole 
                 SC 514 
               
               
                 Mitomycin 
                 Dactinomycin 
                 Quercetin 
               
               
                 Flecainide 
                 Ketoconazole 
                 N-nitrosomorpholine 
               
               
                 sunitinib 
                 Aminoglutethimide 
                 irinotecan 
               
               
                 Apomorphine 
                 thymoglobulin 
                 HC toxin 
               
               
                 methyleugenol 
                 Anti-Retroviral Agents 
                 Dipyridamole 
               
               
                 Berberine 
                 mometasone furoate 
                 Promethazine 
               
               
                 ethotoin 
                 4-hydroxytamoxifen 
                 HI 6 
               
               
                 Diazinon 
                 Flutamide 
                 8-Bromo Cyclic 
               
               
                   
                   
                 Adenosine Monophosphate 
               
               
                 beta-Naphthoflavone 
                 Cardiotoxins 
                 Piracetam 
               
               
                 Dantrolene  
                 Lithium 
                 arsenic trioxide 
               
               
                 Itraconazole 
                 Ozone 
                 scriptaid 
               
               
                 N-Methylaspartate 
                 methylatropine 
                 Econazole 
               
               
                 nimesulide 
                 Diphenhydramine 
                 acadesine 
               
               
                 mono-(2-ethylhexyl)phthalate 
                 vorinostat 
                 Selenomethionine 
               
               
                 Mebendazole 
                 Choline 
                 Iproniazid 
               
               
                 Indomethacin 
                 Dichlororibofuranosylbenzimidazole 
                 Furosemide 
               
               
                 Altretamine 
                 bortezomib 
                 Enoxacin 
               
               
                 Citalopram 
                 Sotalol 
                 atorvastatin 
               
               
                 Pregnenolone 
                 Aspirin 
                 valdecoxib 
               
               
                 Carbonitrile 
                   
                   
               
               
                 olanzapine 
                 meloxicam 
                 Clozapine 
               
               
                 Risperidone 
                 Perphenazine 
                 Chlorpromazine 
               
               
                 Amitriptyline 
                   
                   
               
            
           
           
               
            
               
                 C2. Molecules that downregulate PYCR1: 
               
            
           
           
               
               
               
            
               
                 1 -(5-Isoquinolinesulfonyl)-2- 
                 Aphidicolin 
                 Methylnitrosourea 
               
               
                 Methylpiperazine 
                   
                   
               
               
                 monastrol 
                 Aclarubicin 
                 geldanamycin 
               
               
                 mafosfamide 
                 blebbistatin 
                 Ornidazole 
               
               
                 N-methylpyrrolidone 
                 4-(N-methyl-N- 
                 Dimethyl Sulfoxide 
               
               
                   
                 nitrosamino)-1-(3-pyridyl)-1-butanone 
                   
               
               
                 Disopyramide 
                 Metaproterenol 
                 gefitinib 
               
               
                 sesamin 
                 Immunoglobulin M 
                 Lithium Carbonate 
               
               
                 Mycophenolic Acid 
                 Clofibric Acid 
                 benziodarone 
               
               
                 Idarubicin 
                 enzastaurin 
                 2-(1H-indazol-4-yl)-6-(4-  
               
               
                   
                   
                 methanesulfonylpiperazin- 
               
               
                   
                   
                 1-ylmethyl)-4-morpholin-4- 
               
               
                   
                   
                 ylthieno(3,2-d)pyrimidine 
               
               
                 edelfosine 
                 Doxorubicin 
                 Puromycin 
               
               
                   
                   
                 Aminonucleoside 
               
               
                 bendazolic acid 
                 Daunorubicin 
                 Mycotoxins 
               
               
                 Camptothecin 
                 imatinib 
                 MRK 003 
               
               
                 nickel sulfate 
                 Synephrine 
                 Etoposide 
               
               
                 naringenin 
                 Clofibrate 
                 Coumaphos 
               
               
                 Cycloheximide 
                 Sirolimus 
                 ethaverine 
               
               
                 Gemfibrozil 
                 trichostatin A 
                 Idoxuridine 
               
               
                 imiquimod 
                 Cisplatin 
                 Vincristine 
               
               
                 Protriptyline 
                 CEP 14083 
                 Paroxetine 
               
               
                 decitabine 
                 Benzbromarone 
                 Potassium Dichromate 
               
               
                 hydrastine 
                 tetrahydrozoline 
                 17-(allylamino)-17- 
               
               
                   
                   
                 demethoxygeldanamycin 
               
               
                 Diethylhexyl Phthalate 
                 Fonofos 
                 Dexamethasone 
               
               
                 Minocycline 
                 Streptozocin 
                 pronethalol 
               
               
                 Dihydroergotamine 
                 bamipine 
                 perfluorooctane sulfonic acid 
               
               
                 Dilazep 
                 Ethyl Methanesulfonate 
                 eticlopride 
               
               
                 levocabastine 
                 Santonin 
                 CD 437 
               
               
                 Ceftriaxone 
                 Sulfapyridine 
                 Gonadotropins 
               
               
                 cidofovir 
                 4-acetylaminofluorene 
                 wortmannin 
               
               
                 troglitazone 
                 Hemin 
                 1-Methyl-3-isobutylxanthine 
               
               
                 zardaverine 
                 Simvastatin 
                 Vinblastine 
               
               
                 Prazosin 
                 sulforafan 
                 Fenofibrate 
               
               
                 Mafenide 
                 2-(4-morpholinyl)-8-phenyl- 
                 Curcumin 
               
               
                   
                 4H-1-benzopyran-4-one 
                   
               
               
                 clinafloxacin  
                 Benzo(a)pyrene 
                 buparvaquone 
               
               
                 cyanopindolol 
                 Caffeine 
                 Zimeldine 
               
               
                 Fenoterol 
                 everolimus 
                 2-Acetylaminofluorene 
               
               
                 minaprine 
                 pioglitazone 
                 1-ethyl-2- 
               
               
                   
                   
                 benzimidazolinone 
               
               
                 Dichlorphenamide 
                 methiazole 
                 TO-901317 
               
               
                 8-((4- 
                 Chitosan 
                 4-(5-benzo(1,3)dioxol-5-yl- 
               
               
                 chlorophenyl)thio)cyclic- 
                   
                 4-pyridin-2-yl-1H-imidazol- 
               
               
                 3′,5-AMP 
                   
                 2-yl)benzamide 
               
               
                 Doxepin 
                 alpha-Amino-3-hydroxy-5- 
                 Tretinoin 
               
               
                   
                 methyl-4-isoxazolepropionic Acid 
                   
               
               
                 Bezafibrate 
                 colforsin 
                 Phalloidine 
               
               
                 Diltiazem 
                 Deferoxamine 
                 flubendazole 
               
               
                 biphenylylacetic acid 
                 Oxolinic Acid 
                 SB 203580 
               
               
                 3,3′,5-triiodothyroacetic acid 
                 carcinine 
                 Luteinizing Hormone 
               
               
                 Plicamycin 
                 Phenylbutazone 
                 lapatinib 
               
               
                 15-deoxy-delta(12, 14)-prostaglandin J2 
                 Enalapril 
                 Allantoin 
               
               
                 diloxanide furoate 
                 Etidronic Acid 
                 Metribolone 
               
               
                 chelidonine 
                 marimastat 
                 Chorionic Gonadotropin 
               
               
                 fenspiride 
                 Valproic Acid 
                 Clonidine 
               
               
                 dibenzazepine 
                 gabazine 
                 Corticosterone 
               
               
                 vinylidene chloride 
                 Thioguanine 
                 Ethionine 
               
               
                 Isoetharine 
                 Vidarabine 
                 LPS 9 
               
               
                 letrozole 
                 salsolidine 
                 Betazole 
               
               
                 Oxymetazoline 
                 Ethylnitrosourea 
                 Dextran Sulfate 
               
               
                 linalool 
                 NG-Nitroarginine Methyl Ester 
                 Pyrantel 
               
               
                 Zinc Oxide 
                 Fusaric Acid 
                 Tetradecanoylphorbol Acetate 
               
               
                 Ranitidine 
                 Dexfenfluramine 
                 canadine 
               
               
                 mycophenolate mofetil 
                 rosiglitazone 
                 AICA ribonucleotide 
               
               
                 Metolazone 
                 Tolazoline 
                 Alprostadil 
               
               
                 Oxazepam 
                 Colchicine 
                 Mefenamic Acid 
               
               
                 dexchlorpheniramine 
                 alginic acid 
                 Sulpiride 
               
               
                 Dinoprost 
                 Acetylcysteine 
                 systhane 
               
               
                 Finasteride 
                 vinorelbine 
                 Fluphenazine 
               
               
                 gemcitabine 
                 erlotinib 
                 Raloxifene 
               
               
                 1,2-dilinolenoyl-3-(4- 
                 bis(tri-n-butyltin)oxide 
                 Pergolide 
               
               
                 aminobutyryl)propane-1,2,3-triol 
                   
                   
               
               
                 Ascorbic Acid 
                 Monocrotaline 
                 Papaverine 
               
               
                 Imipramine 
                 Trifluoperazine 
                 Phenol 
               
               
                 Metformin 
                 benzyloxycarbonylleucyl- 
                 triadimefon 
               
               
                   
                 leucyl-leucine aldehyde 
                   
               
               
                 Rifampin 
                 leflunomide 
                 nimetazepam 
               
               
                 Methyl Methanesulfonate 
                 Dimethylnitrosamine 
                 Ajmaline 
               
               
                 Tetracycline 
                 Cefuroxime 
                 monorden 
               
               
                 cobaltous chloride 
                 Paraquat 
                 Chlorambucil 
               
               
                 naphthalan 
                 Chlorpheniramine 
                 Emetine 
               
               
                 terbinafine 
                 lansoprazole 
                 Methotrexate 
               
               
                 Nicotine 
                 Cyclophosphamide 
                 Diethylnitrosamine 
               
               
                 Prochlorperazine 
                 Haloperidol 
                 Quinidine 
               
               
                 Digoxin 
                 Losartan 
                 fluvastatin 
               
               
                 Puromycin 
                 Cytarabine 
                 Paclitaxel 
               
               
                 pirinixic acid 
                 Tranylcypromine 
                 dasatinib 
               
               
                 resveratrol 
                 carvedilol 
                 Ribavirin 
               
               
                 Calcitriol 
                 Ofloxacin 
                 Rolipram 
               
               
                 Amiodarone  
                 Thioridazine 
                 Lovastatin 
               
               
                 Fluoxetine 
                   
                   
               
            
           
           
               
            
               
                 D1. Molecules that upregulate ALDH18A1: 
               
            
           
           
               
               
               
            
               
                 halofuginone 
                 bestatin 
                 Tunicamycin 
               
               
                 Ecdysterone 
                 beta-cyclodextrin- 
                 Methapyrilene 
               
               
                   
                 benzaldehyde 
                   
               
               
                 Vanadates 
                 Captopril 
                 Dimethylnitrosamine 
               
               
                 ONO 2235 
                 Azathioprine 
                 Thapsigargin 
               
               
                 Loratadine 
                 acodazole 
                 Biperiden 
               
               
                 Stanozolol 
                 3-nitropropionic acid 
                 Clodronic Acid 
               
               
                 Naloxone 
                 enterotoxin B, 
                 rifapentine 
               
               
                   
                 staphylococcal 
                   
               
               
                 1,3-dichloro-2-propanol 
                 sildenafil 
                 Glycocholic Acid 
               
               
                 Hypericum extract LI 160 
                 irbesartan 
                 sulconazole 
               
               
                 apicidin 
                 Paroxetine 
                 Lomustine 
               
               
                 balsalazide 
                 Cyclosporine 
                 U 0126 
               
               
                 cetraxate 
                 amineptin 
                 Ethambutol 
               
               
                 ascorbate-2-phosphate 
                 Levodopa 
                 Capsaicin 
               
               
                 Calcium 
                 4,4′-diaminodiphenylmethane 
                 Etodolac 
               
               
                 Cardiotoxins 
                 Carmustine 
                 Allopurinol 
               
               
                 Acetaminophen 
                 Indinavir 
                 SB 203580 
               
               
                 Piracetam 
                 valdecoxib 
                 Niridazole 
               
               
                 Altretamine 
                 lornoxicam 
                 Ethylnitrosourea 
               
               
                 Ethionamide 
                 Diflunisal 
                 6-Mercaptopurine 
               
               
                 Hyaluronic Acid 
                 Busulfan 
                 Doxepin 
               
               
                 Fluphenazine 
                 cyanoginosin LR 
                 Salicylic Acid 
               
               
                 Isoproterenol 
                 Promazine 
                 Clomipramine 
               
               
                 Rifampin 
                 Thioacetamide 
                 tetrandrine 
               
               
                 amprenavir 
                 LG 268 
                 Ketoconazole 
               
               
                 pristane 
                 Ampicillin 
                 Albendazole 
               
               
                 Itraconazole 
                 Triiodothyronine 
                 Muromonab-CD3 
               
               
                 fulvestrant 
                 nimesulide 
                 meloxicam 
               
               
                 telmisartan 
                 Raloxifene 
                 Bromisovalum 
               
               
                 Terbutaline 
                 Nitrofurazone 
                 tracazolate 
               
               
                 6-bromoindirubin-3′-oxime 
                 Bleomycin 
                 vinylidene chloride 
               
               
                 valsartan 
                 geraniol 
                 Progesterone 
               
               
                 lacidipine 
                 tropisetron 
                 4-(4-fluorophenyl)-2-(4- 
               
               
                   
                   
                 hydroxyphenyl)-5-(4- 
               
               
                   
                   
                 pyridyl)imidazole 
               
               
                 Sulindac 
                 enterotoxin I, staphylococcal 
                 eperisone 
               
               
                 Stavudine 
                 estradiol 3-benzoate 
                 testosterone 17 
               
               
                   
                   
                 beta-cypionate 
               
               
                 Thiorphan 
                 Podophyllotoxin 
                 Doxapram 
               
               
                 ferulic acid 
                 Ethinyl Estradiol 
                 ovalicin 
               
               
                 Pentobarbital 
                 Ethionine 
                 Tetracycline 
               
               
                 Cyproterone Acetate 
                 desloratadine 
                 Vinblastine 
               
               
                 olanzapine 
                 lead acetate 
                 Chloroform 
               
               
                 Isotretinoin 
                 artemisinine 
                 pirenperone 
               
               
                 Aspirin 
                 Diethylstilbestrol 
                 Diclofenac 
               
               
                 N-(2-aminophenyl)-4-(N-(pyridin-3- 
                 Estradiol 
                 Mebendazole 
               
               
                 ylmethoxycarbonyl)aminomethyl)benzamide 
                   
                   
               
               
                 Valproic Acid 
                 pantoprazole 
                 Ticrynafen 
               
               
                 Isoflurophate 
                 Lithium Carbonate 
                 Labetalol 
               
               
                 lansoprazole 
                 Carbon Tetrachloride 
                 Particulate Matter 
               
               
                 1-amino-2,4-dibromoanthraquinone 
                 clorsulon 
                 Pentylenetetrazole 
               
               
                 Lead 
                 tris(2,3-dibromopropyl)phosphate 
                 Pregnenolone Carbonitrile 
               
               
                 alginic acid 
                 ciclopirox 
                 Phenylephrine 
               
               
                 Teriparatide 
                 Glipizide 
                 thymoglobulin 
               
               
                 Folic Acid 
                 Ozone 
                 linezolid 
               
               
                 Oxyquinoline 
                 Clotrimazole 
                 fazarabine 
               
               
                 8-Bromo Cyclic Adenosine 
                 Serotonin 
                 Caerulein 
               
               
                 Monophosphate 
                   
                   
               
               
                 Neostigmine 
                 Lithium 
                 Proglumide 
               
               
                 Morantel 
                 Saquinavir 
                 CpG ODN 2216 
               
               
                 Dipyrone 
                 Tinidazole 
                 Cisapride 
               
               
                 Glycerol 
                 Mannitol 
                 Chlormadinone Acetate 
               
               
                 Memantine 
                 Minoxidil 
                 Tetracaine 
               
               
                 1,5-naphthalenediamine 
                 Monensin 
                 nateglinide 
               
               
                 bromodichloromethane 
                 Phytohemagglutinins 
                 Insulin 
               
               
                 erlotinib 
                 Trifluridine 
                 zomepirac 
               
               
                 Aminosalicylic Acid 
                 Amitriptyline 
                 Hydrogen Peroxide 
               
               
                 2,4-diaminotoluene 
                 Triacetin 
                 Mestranol 
               
               
                 Ethanol 
                 4′-N-benzoylstaurosporine 
                 ferric nitrilotriacetate 
               
               
                 Nortriptyline 
                 Thiamphenicol 
                 Metformin 
               
               
                 benzyloxycarbonylleucyl-leucyl-leucine 
                 Risperidone 
                 Calcitriol 
               
               
                 aldehyde 
                   
                   
               
               
                 Pyrethrins 
                 Melphalan 
                 BCG Vaccine 
               
               
                 R 848 
                 4-acetylaminofluorene 
                 bortezomib 
               
               
                 Diphenhydramine 
                 procyanidin 
                 Soman 
               
               
                 Tranexamic Acid 
                 Atovaquone 
                 Cyclophosphamide 
               
               
                 Pempidine 
                 Luteolin 
                 Metaraminol 
               
               
                 Indomethacin 
                 HI 6 
                 Citric Acid 
               
               
                 Omeprazole 
                 anastrozole 
                 Diethylnitrosamine 
               
               
                 N-acetylsphingosine 
                 Imipramine 
                 Curcumin 
               
               
                 Ritonavir 
                 Lobeline 
                 Ipratropium 
               
               
                 Digitoxin 
                 temsirolimus 
                 Ionomyin 
               
               
                 Metoprolol 
                 flavopiridol 
                 1-Methyl-4-phenyl-1,2,3,6- 
               
               
                   
                   
                 tetrahydropyridine 
               
               
                 Promethazine 
                 Lamivudine 
                 Streptomycin 
               
               
                 Tubocurarine 
                 Vitamin E 
                 Nitrendipine 
               
               
                 Riluzole 
                 Glycine 
                 2,2′-Dipyridyl 
               
               
                 Enalapril 
                 Doxazosin 
                 Aphidicolin 
               
               
                 Amlodipine 
                 Ketoprofen 
                 benazepril 
               
               
                 Hydrochlorothiazide 
                 Vincristine 
                 dexchlorpheniramine 
               
               
                 Nisoldipine 
                 Lisinopril 
                 Alpha-Amanitin 
               
               
                 doxofylline 
                 Piroxicam 
                 Dimenhydrinate 
               
               
                 Amphetamine 
                 Cimetidine 
                 Naproxen 
               
               
                 Ketorolac 
                 Citalopram 
                 tenidap 
               
               
                 efavirenz 
                 Sulpiride 
                 4-(5-benzo(1,3)dioxol-5-yl-4- 
               
               
                   
                   
                 pyridin-2-yl-1H-imidazol-2- 
               
               
                   
                   
                 yl)benzamide 
               
               
                 candesartan 
                 gemcitabine 
                 ochratoxin A 
               
               
                 Ribavirin 
                 Deoxyglucose 
                 Chitosan 
               
               
                 Nevirapine 
                 Miconazole 
                 Nicotine 
               
               
                 Hydroxyurea 
                 Ticlopidine 
                 Sarin 
               
               
                 Nafenopin 
                 Atropine 
                   
               
            
           
           
               
            
               
                 D2. Molecules that downregulate ALDH18A1: 
               
            
           
           
               
               
               
            
               
                 neuropeptide Y (18-36) 
                 Platelet Activating Factor 
                 Chloroquine 
               
               
                 sodium chromate(VI) 
                 GW 501516 
                 Methylnitronitrosoguanidine 
               
               
                 troglitazone 
                 Natriuretic Peptide, C-Type 
                 scriptaid 
               
               
                 1-hydroxycholecalciferol 
                 amitraz 
                 Perhexiline 
               
               
                 Terfenadine 
                 Amiodarone 
                 hexachloroethane 
               
               
                 Prostaglandins E 
                 Gentian Violet 
                 Rolipram 
               
               
                 Zalcitabine 
                 Vecuronium Bromide 
                 HC toxin 
               
               
                 Ethylestrenol 
                 vinorelbine 
                 AICA ribonucleotide 
               
               
                 torsemide 
                 sodium selenate 
                 Mephentermine 
               
               
                 8-aminohexylamino cAMP 
                 artemether 
                 Idarubicin 
               
               
                 Fluocinolone Acetonide 
                 Thioguanine 
                 Humic Substances 
               
               
                 monastrol 
                 trovafloxacin 
                 insulin-like growth factor I (57-70) 
               
               
                 Hexachlorophene 
                 benoxaprofen 
                 rofecoxib 
               
               
                 rosiglitazone 
                 Chlorpyrifos 
                 Shiga Toxin 
               
               
                 Methylnitrosourea 
                 Fluoxetine 
                 Cyclandelate 
               
               
                 Etoposide 
                 methyl salicylate 
                 Tolazoline 
               
               
                 Acrolein 
                 Benzocaine 
                 zardaverine 
               
               
                 Roflumilast 
                 parbendazole 
                 Methyl Methanesulfonate 
               
               
                 CPG-oligonucleotide 
                 zopiclone 
                 ibufenac 
               
               
                 carvedilol 
                 Methylcholanthrene 
                 benzyloxycarbonylvalyl-alanyl- 
               
               
                   
                   
                 aspartyl fluoromethyl ketone 
               
               
                 quintozene 
                 4-dichlorobenzene 
                 Sulfadiazine 
               
               
                 Clofibrate 
                 Puromycin Aminonucleoside 
                 hydrastine 
               
               
                 Metronidazole 
                 Menthol 
                 beta-Naphthoflavone 
               
               
                 Sirolimus 
                 Dexfenfluramine 
                 sodium arsenite 
               
               
                 Cisplatin 
                 Daunorubicin 
                 2-Acetylaminofluorene 
               
               
                 Phenobarbital 
                 Simvastatin 
                 Camptothecin 
               
               
                 Niacin 
                 Tacrine 
                 Sotalol 
               
               
                 Nifedipine 
                 nitrosobenzylmethylamine 
                 Alprazolam 
               
               
                 fenspiride 
                 Immunoglobulin M 
                 mafosfamide 
               
               
                 Doxorubicin 
                 Dichlorvos 
                 Dihydrostreptomycin Sulfate 
               
               
                 Clofazimine 
                 Ceftazidime 
                 Niacinamide 
               
               
                 Emodin 
                 naphthalan 
                 clinafloxacin 
               
               
                 naphthalenediimide 
                 rabeprazole 
                 Diazinon 
               
               
                 Propantheline 
                 Pergolide 
                 6-methoxy-2- 
               
               
                   
                   
                 naphthylacetic acid 
               
               
                 Digoxin 
                 Probenecid 
                 Pimozide 
               
               
                 Carboplatin 
                 benfluorex 
                 terbinafine 
               
               
                 Tetrachlorodibenzodioxin 
                 Ampyrone 
                 Mafenide 
               
               
                 tetrahydrozoline 
                 Lindane 
                 phosphonoacetamide 
               
               
                 Maprotiline 
                 Neomycin 
                 infliximab 
               
               
                 2-methoxyestradiol 
                 Finasteride 
                 Dexamethasone 
               
               
                 Methylene Chloride 
                 Cycloheximide 
                 1-(5-Isoquinolinesulfonyl)- 
               
               
                   
                   
                 2-Methylpiperazine 
               
               
                 Flavoxate 
                 Hydralazine 
                 Etidronic Acid 
               
               
                 Poly I-C 
                 Mercuric Chloride 
                 zileuton 
               
               
                 trichostatin A 
                 DDT 
                 Methotrexate 
               
               
                 atorvastatin 
                 Bismuth 
                 oxcarbazepine 
               
               
                 tosufloxacin 
                 piclamilast 
                 Vidarabine 
               
               
                 Anti-Retroviral Agents 
                 Benzo(a)pyrene 
                 cerivastatin 
               
               
                 cobaltous chloride 
                 Propylthiouracil 
                 Erythromycin 
               
               
                 Hydrocortisone 
                 Bepridil 
                 Caffeine 
               
               
                 Benserazide 
                 LBH589 
                 Amikacin 
               
               
                 Trifluoperazine 
                 Harmaline 
                 Fenofibrate 
               
               
                 tranilast 
                 chromium hexavalention 
                 Aflatoxin B1 
               
               
                 gabapentin 
                 lomefloxacin 
                 fomepizole 
               
               
                 Metoclopramide 
                 Chlorpropamide 
                 Phenol 
               
               
                 Histidinol 
                 Chlorpromazine 
                 chelidonine 
               
               
                 myricetin 
                 Bezafibrate 
                 letrozole 
               
               
                 phenacemide 
                 everolimus 
                 edelfosine 
               
               
                 Clonidine 
                 imatinib 
                 celecoxib 
               
               
                 Pravastatin 
                 Prochlorperazine 
                 nifenazone 
               
               
                 Granisetron 
                 oxiconazole 
                 Isoniazid 
               
               
                 phorbolol myristate acetate 
                 Suloctidil 
                 Albuterol 
               
               
                 Acetazolamide 
                 Diethylhexyl Phthalate 
                 Ethosuximide 
               
               
                 Halothane 
                 tenofovir 
                 1,2,3-trichloropropane 
               
               
                 Metaproterenol 
                 N-(2-cyclohexyloxy-4- 
                 Fusaric Acid 
               
               
                   
                 nitrophenyl)methanesulfonamide 
                   
               
               
                 beta-1,3-glucan 
                 ipriflavone 
                 Fluconazole 
               
               
                 2-(1H-indazol-4-yl)-6-(4- 
                 Inosine Monophosphate 
                 hydrazine 
               
               
                 methanesulfonylpiperazin-1-ylmethyl)-4- 
                   
                   
               
               
                 morpholin-4-ylthieno(3,2-d)pyrimidine 
                   
                   
               
               
                 Betamethasone 
                 isoconazole 
                 Cyproheptadine 
               
               
                 Gonadotropins 
                 Sumatriptan 
                 Dihydroergotamine 
               
               
                 Furosemide 
                 Fluspirilene 
                 Ciprofloxacin 
               
               
                 Azaguanine 
                 Mifepristone 
                 Clarithromycin 
               
               
                 Gentamicins 
                 arsenic trioxide 
                 Dihydroergocristine 
               
               
                 decitabine 
                 Ultraviolet Rays 
                 Genistein 
               
               
                 Sertraline 
                 Ethylene Glycol 
                 Zinc Oxide 
               
               
                 Sulfaphenazole 
                 Rifabutin 
                 4-octylphenol 
               
               
                 hydroquinone 
                 Paclitaxel 
                 Foscarnet 
               
               
                 lingzhi 
                 tazobactam 
                 Bithionol 
               
               
                 Furazolidone 
                 calycanthine 
                 Thioridazine 
               
               
                 2-(4-morpholinyl)-8-phenyl-4H-1- 
                 Iproniazid 
                 Flutamide 
               
               
                 benzopyran-4-one 
                   
                   
               
               
                 diphenylpyraline 
                 Chorionic Gonadotropin 
                 2-dichlorobenzene 
               
               
                 15-deoxy-delta(12, 14)- 
                 Dinoprost 
                 hexachlorobutadiene 
               
               
                 prostaglandin J2 
                   
                   
               
               
                 Clozapine 
                 CEP 14083 
                 pioglitazone 
               
               
                 betulinic acid 
                 Fludrocortisone 
                 Lovastatin 
               
               
                 Pyridoxine 
                 Sulfadoxine 
                 Acetylcysteine 
               
               
                 glycidol 
                 isocorydine 
                 blebbistatin 
               
               
                 1,3-dichlorobenzene 
                 Clofibric Acid 
                 X-Rays 
               
               
                 1-ethyl-2-benzimidazolinone 
                 Troleandomycin 
                 boldine 
               
               
                 Tretinoin 
                 Amoxapine 
                 Pregnenolone 
               
               
                 Tolazamide 
                 Ethacrynic Acid 
                 Coumaphos 
               
               
                 5-episisomicin 
                 oxaliplatin 
                 Cefadroxil 
               
               
                 pyrvinium 
                 Monocrotaline 
                 Tramadol 
               
               
                 harmol 
                 Phenelzine 
                 fluvastatin 
               
               
                 ethotoin 
                 Puromycin 
                 Ergocalciferols 
               
               
                 oltipraz 
                 Penicillamine 
                 acemetacin 
               
               
                 dexibuprofen 
                 Piperonyl Butoxide 
                 Topotecan 
               
               
                 Choline 
                 PI103 
                 dorzolamide 
               
               
                 Dantrolene 
                 Norethindrone 
                 Bromocriptine 
               
               
                 Gossypol 
                 bisphenol A 
                 Alprostadil 
               
               
                 Carbachol 
                 repaglinide 
                 Melatonin 
               
               
                 Clonazepam 
                 Quinacrine 
                 Moxalactam 
               
               
                 Domperidone 
                 Bisacodyl 
                 Prednisolone 
               
               
                 phenethyl isothiocyanate 
                 Butyric Acid 
                 ebastine 
               
               
                 Malathion 
                 Azacitidine 
                 Lorazepam 
               
               
                 Ethyl Methanesulfonate 
                 Nitric Oxide 
                 1-Methyl-3-isobutylxanthine 
               
               
                 geldanamycin 
                 Nimodipine 
                 Colchicine 
               
               
                 Fluvoxamine 
                 Nystatin 
                 monorden 
               
               
                 Mitomycin 
                 Atenolol 
                 vorinostat 
               
               
                 Chlorambucil 
                 NG-Nitroarginine Methyl Ester 
                 Metergoline 
               
               
                 irinotecan 
                 Netilmicin 
                 gefitinib 
               
               
                 3-deazaneplanocin 
                 Benperidol 
                 Deferoxamine 
               
               
                 Y 27632 
                 canadine 
                 Losartan 
               
               
                 Dizocilpine Maleate 
                 Cytarabine 
                 Haloperidol 
               
               
                 Clemastine 
                 resveratrol 
                 dibenzazepine 
               
               
                 Enoxacin 
                 Rotenone 
                 Amiloride 
               
               
                 Prazosin 
                 Terazosin 
                 Quercetin 
               
               
                 17-(allylamino)-17- 
                 mono-(2-ethylhexyl)phthalate 
                 Gemfibrozil 
               
               
                 demethoxygeldanamycin 
                   
                   
               
               
                 SU 5402 
                 Emetine 
                 Flunarizine 
               
               
                 Plicamycin 
                 Vitamin K 3 
                 4-hydroxy-2-nonenal 
               
               
                 Nocodazole 
                 Fenoprofen 
                 Zidovudine 
               
               
                 Ranitidine 
                 Dicyclomine 
                 Mycophenolic Acid 
               
               
                 compactin 
                 dasatinib 
                 leflunomide 
               
               
                 Econazole 
                 Galantamine 
                 Diazepam 
               
               
                 lysophosphatidic acid 
                 8-((4-chlorophenyl)thio)cyclic- 
                 Dactinomycin 
               
               
                   
                 3′,5′-AMP 
                   
               
               
                 Ofloxacin 
                 Fluorouracil 
                 Oxymetazoline 
               
               
                 Papaverine 
                 Ifosfamide 
                 Amantadine 
               
               
                 Disulfiram 
                 Methyldopa 
                   
               
            
           
           
               
            
               
                 E1. Molecules that upregulate OAT: 
               
            
           
           
               
               
               
            
               
                 Forskolin 
                 LBH589 
                 fipronil 
               
               
                 sorafenib 
                 riddelliine 
                 Sirolimus 
               
               
                 trichostatin A 
                 decitabine 
                 tetra(4-N- 
               
               
                   
                   
                 methylpyridyl)porphine 
               
               
                 testosterone 17 beta-cypionate 
                 Sodium Benzoate 
                 Aphidicolin 
               
               
                 Diquat 
                 bevacizumab 
                 ellipticine 
               
               
                 Amitrole 
                 benzimidazole 
                 Ecdysterone 
               
               
                 marimastat 
                 Copper Sulfate 
                 dasatinib 
               
               
                 Sulpiride 
                 Cantharidin 
                 erlotinib 
               
               
                 Meptazinol 
                 4,4′-diaminodiphenylmethane 
                 Aclarubicin 
               
               
                 Idoxuridine 
                 Diethylhexyl Phthalate 
                 Tolnaftate 
               
               
                 sulforafan 
                 2-nitrofluorene 
                 thermozymocidin 
               
               
                 fludarabine 
                 Theophylline 
                 suxibuzone 
               
               
                 Valproic Acid 
                 beta-Naphthoflavone 
                 HC toxin 
               
               
                 Methylnitrosourea 
                 1-ethyl-2-benzimidazolinone 
                 vorinostat 
               
               
                 Molindone 
                 Triiodothyronine 
                 cidofovir 
               
               
                 Pyrethrins 
                 Fenoterol 
                 Aflatoxins 
               
               
                 butamben 
                 diisopropyl 
                 Paraquat 
               
               
                   
                 methylphosphonate 
                   
               
               
                 Thapsigargin 
                 Mannitol 
                 geldanamycin 
               
               
                 monastrol 
                 Hycanthone 
                 Pregnenolone Carbonitrile 
               
               
                 Ofloxacin 
                 Thiostrepton 
                 bafilomycin A 
               
               
                 tripterine 
                 tenidap 
                 4-cyclododecyl-2,6- 
               
               
                   
                   
                 dimethylmorpholine acetate 
               
               
                 senecionine 
                 Vincristine 
                 Benzalkonium Compounds 
               
               
                 Methyldopa 
                 zardaverine 
                 Phenylmercuric Acetate 
               
               
                 Papaverine 
                 Isoniazid 
                 Fenofibrate 
               
               
                 sanguinarine 
                 Haloperidol 
                 Pregnenolone 
               
               
                 Metribolone 
                 2-methoxyestradiol 
                 phenethyl isothiocyanate 
               
               
                 imatinib 
                 Cam ptothecin 
                 Ozone 
               
               
                 blebbistatin 
                 Gabexate 
                 4-nonylphenol 
               
               
                 Amphetamine 
                 Clodronic Acid 
                 Methylprednisolone 
               
               
                 VX 
                 Cytokines 
                 Dihydrotestosterone 
               
               
                 Tretinoin 
                 doxofylline 
                 Thioctic Acid 
               
               
                 Fenoprofen 
                 oxaprozin 
                 cerivastatin 
               
               
                 Yellow Fever Vaccine 
                 Hemin 
                 N-methylpyrrolidone 
               
               
                 Zidovudine 
                 Etidronic Acid 
                 tenofovir 
               
               
                 Diflunisal 
                 isoconazole 
                 trilinolein 
               
               
                 Methanol 
                 Folic Acid 
                 Clofibrate 
               
               
                 nimesulide 
                 Fluphenazine 
                 Quercetin 
               
               
                 Botulinum Toxins, Type A 
                 Prostaglandins E 
                 Acrolein 
               
               
                 Cefuroxime 
                 Chlorpheniramine 
                 Tetanus Toxin 
               
               
                 Ribavirin 
                 bis(tri-n-butyltin)oxide 
                 Methylcholanthrene 
               
               
                 heliotrine 
                 triptolide 
                 ciclopirox 
               
               
                 Bupropion 
                 Clenbuterol 
                 Dicyclomine 
               
               
                 Strophanthidin 
                 gefitinib 
                 Hydrogen Peroxide 
               
               
                 gedunin 
                 Caffeine 
                 Trenbolone Acetate, 
               
               
                   
                   
                 (17beta)-isomer 
               
               
                 atorvastatin 
                 romidepsin 
                 Hydroxyurea 
               
               
                 Flurbiprofen 
                 Nevirapine 
                 Moxisylyte 
               
               
                 Cytochalasin B 
                 pristane 
                 bicalutamide 
               
               
                 Cholera Toxin 
                 Zalcitabine 
                 gamma-Tocopherol 
               
               
                 8-Bromo Cyclic Adenosine 
                 Anti-Retroviral Agents 
                 Phenylbutazone 
               
               
                 Monophosphate 
                   
                   
               
               
                 8-((4- 
                 1-(5-Isoquinolinesulfonyl)-2- 
                 Corticosterone 
               
               
                 chlorophenyl)thio)cyclic- 
                 Methylpiperazine 
                   
               
               
                 3′,5-AMP 
                   
                   
               
               
                 thymoglobulin 
                 Insulin 
                 cathelicidin antimicrobial 
               
               
                   
                   
                 peptide 
               
               
                 everolimus 
                 BCG Vaccine 
                 X-Rays 
               
               
                 letrozole 
                 Mycophenolic Acid 
                 Doxepin 
               
               
                 Enalapril 
                 NG-Nitroarginine Methyl 
                 Dimethyl Sulfoxide 
               
               
                   
                 Ester 
                   
               
               
                 Metoprolol 
                 Methotrexate 
                 Furosemide 
               
               
                 Enoxacin 
                 alpha-Tocopherol 
                 Cyclosporine 
               
               
                 Phenylephrine 
                 4-methyl-N-(3-(4- 
                 Deferoxamine 
               
               
                   
                 methylimidazol-1-yl)-5- 
                   
               
               
                   
                 (trifluoromethyl)phenyl)-3- 
                   
               
               
                   
                 ((4-pyridin-3-ylpyrimidin-2- 
                   
               
               
                   
                 yl)amino)benzamide 
                   
               
               
                 Rifampin 
                 Vinblastine 
                 Amitriptyline 
               
               
                 Quinidine 
                 oxybutynin 
                 Dactinomycin 
               
               
                 lysophosphatidic acid 
                 Atropine 
                 resveratrol 
               
               
                 Terbutaline 
                 Paroxetine 
                 17-(allylamino)-17- 
               
               
                   
                   
                 demethoxygeldanamycin 
               
               
                 Losartan 
                 Albendazole 
                 Diphenhydramine 
               
               
                 Fluoxetine 
                 Fluorouracil 
                 bisphenol A 
               
               
                 acetopyrrothine 
                 1-Methyl-3-isobutylxanthine 
                 Cytarabine 
               
               
                 Vitamin K 3 
                 Paclitaxel 
                 Benomyl 
               
            
           
           
               
            
               
                 E2. Molecules that downregulate OAT 
               
            
           
           
               
               
               
            
               
                 Thioacetamide 
                 Ticlopidine 
                 bendazolic acid 
               
               
                 Dimethylnitrosamine 
                 Hexachlorobenzene 
                 methylformamide 
               
               
                 Chlormezanone 
                 coumarin 
                 bromobenzene 
               
               
                 Flutamide  
                 Ethambutol 
                 lornoxicam 
               
               
                 Piperonyl Butoxide 
                 Clonazepam 
                 nitrosobenzylmethylamine 
               
               
                 N-nitrosomorpholine 
                 Propylthiouracil 
                 Diethylnitrosamine 
               
               
                 1,3-dichloro-2-propanol 
                 pantoprazole 
                 Methimazole 
               
               
                 Am inoglutethim ide 
                 Hexamethonium 
                 Carbamazepine 
               
               
                 artemisinine 
                 1,2-dithiol-3-thione 
                 oltipraz 
               
               
                 Chloroform 
                 Monocrotaline 
                 4-dichlorobenzene 
               
               
                 Ethionamide 
                 Stavudine 
                 Asbestos 
               
               
                 hydroxytamoxifen 
                 Carbimazole 
                 Phenobarbital 
               
               
                 ochratoxin A 
                 Pyrogallol 
                 Disopyramide 
               
               
                 Gemfibrozil 
                 alachlor 
                 Carbon Tetrachloride 
               
               
                 2-dichlorobenzene 
                 Acetaminophen 
                 Cinnarizine 
               
               
                 Chloramphenicol 
                 2-Acetylaminofluorene 
                 terbinafine 
               
               
                 Naproxen 
                 Colchicine 
                 Lorazepam 
               
               
                 gentamicin C 
                 salicylamide 
                 Econazole 
               
               
                 estradiol 3-benzoate 
                 Omeprazole 
                 bambuterol 
               
               
                 Phenacetin 
                 garcinol 
                 Gentian Violet 
               
               
                 Okadaic Acid 
                 Phenytoin 
                 Clotrimazole 
               
               
                 Testosterone 
                 iodoform 
                 Trimethadione 
               
               
                 Citrinin 
                 Hydroxyzine 
                 nimetazepam 
               
               
                 Polychlorinated Biphenyls 
                 crotamiton 
                 benziodarone 
               
               
                 iturelix 
                 Dehydroepiandrosterone 
                 Mestranol 
               
               
                 Methyltestosterone 
                 Etodolac 
                 Miconazole 
               
               
                 Dantrolene 
                 PI103 
                 Safrole 
               
               
                 Estriol 
                 Niclosamide 
                 Ibuprofen 
               
               
                 Malathion 
                 Penicillamine 
                 Calcium Chloride 
               
               
                 Carmustine 
                 Methapyrilene 
                 lead tetraacetate 
               
               
                 vanadyl sulfate 
                 Benperidol 
                 dexamisole 
               
               
                 Procarbazine 
                 hexachlorobutadiene 
                 Benzbromarone 
               
               
                 Methylene Chloride 
                 Cymarine 
                 ranolazine 
               
               
                 Azathioprine  
                 Chromium 
                 Famotidine 
               
               
                 Tryptophan 
                 Lead 
                 Ketanserin 
               
               
                 Atovaquone 
                 Phleomycins 
                 Trypsin Inhibitor, Bowman- 
               
               
                   
                   
                 Birk Soybean 
               
               
                 Amanitins 
                 meloxicam 
                 Sulfasalazine 
               
               
                 Mifepristone 
                 Salicylates 
                 Dinoprostone 
               
               
                 Sulindac 
                 5′-methylthioadenosine 
                 Patulin 
               
               
                 Danazol 
                 Doxorubicin 
                 Metolazone 
               
               
                 pioglitazone 
                 zileuton 
                 Canavanine 
               
               
                 Dizocilpine Maleate 
                 Urethane 
                 Tacrine 
               
               
                 sodium chromate(VI) 
                 Estradiol 
                 Disulfiram 
               
               
                 fosfosal 
                 4-(5-benzo(1,3)dioxol-5-yl- 
                 fenamiphos 
               
               
                   
                 4-pyridin-2-yl-1H-imidazol- 
                   
               
               
                   
                 2-yl)benzamide 
                   
               
               
                 Vancomycin 
                 Dimethylformamide 
                 Lomustine 
               
               
                 Luteolin 
                 Lasalocid 
                 naphthalene 
               
               
                 Diazepam 
                 perfluorooctanoic acid 
                 2,4-Dinitrophenol 
               
               
                 phenothiazine 
                 Nitrazepam 
                 acetovanillone 
               
               
                 acadesine 
                 Gentamicins 
                 Diltiazem 
               
               
                 Ketorolac 
                 shikonin 
                 Edrophonium 
               
               
                 Isotretinoin 
                 rabeprazole 
                 Fursultiamin 
               
               
                 Lidocaine 
                 Fluocinolone Acetonide 
                 Genistein 
               
               
                 Minocycline 
                 syrosingopine 
                 GW 3965 
               
               
                 Thiabendazole 
                 Ethinyl Estradiol 
                 Itraconazole 
               
               
                 Fluorometholone 
                 3-deazaneplanocin 
                 Fluconazole 
               
               
                 Diethylstilbestrol 
                 Cyproterone Acetate 
                 Promethazine 
               
               
                 rosiglitazone 
                 aristolochic acid 1 
                 Cisplatin 
               
               
                 scriptaid 
                 Ganciclovir 
                 Emetine 
               
               
                 Diclofenac 
                 lingzhi 
                 ferric nitrilotriacetate 
               
               
                 Ethionine 
                 Khellin 
                 hydrazine 
               
               
                 Canrenoate Potassium 
                 Nystatin 
                 9-(2-hydroxy-3- 
               
               
                   
                   
                 nonyl)adenine 
               
               
                 Tunicamycin 
                 systhane 
                 Caerulein 
               
               
                 Phenylalanine 
                 Calcium 
                 Clofibric Acid 
               
               
                 arsenic trioxide 
                 Hemicholinium 3 
                 Ethylnitrosourea 
               
               
                 sodium arsenite 
                 Remoxipride 
                 Oxazepam 
               
               
                 Dexamethasone 
                 Hydrocortisone 
                 dirithromycin 
               
               
                 homatropine 
                 U 0126 
                 Clobetasol 
               
               
                 triadimefon 
                 Melphalan 
                 Zimeldine 
               
               
                 Antigen-Antibody Complex 
                 Nitrofurazone 
                 Ethanol 
               
               
                 cephaelin 
                 apratoxin A 
                 Aspirin 
               
               
                 arsenic acid 
                 Betamethasone 
                 furaltadon 
               
               
                 flunixin 
                 1,3-dichlorobenzene 
                 anastrozole 
               
               
                 nifuroxazide 
                 Lovastatin 
                 Pivampicillin 
               
               
                 Nifedipine 
                 Tolazoline 
                 Nocodazole 
               
               
                 tropisetron 
                 Orotic Acid 
                 Simvastatin 
               
               
                 Carcinogens 
                 CpG ODN 2216 
                 isoxicam 
               
               
                 naftopidil 
                 leflunomide 
                 Nicotine 
               
               
                 Dihydroergotamine 
                 acidocin CH5,  Lactobacillus   
                 Bezafibrate 
               
               
                   
                 
                   acidophilus 
                 
                   
               
               
                 Serotonin 
                 Allopurinol 
                 Spironolactone 
               
               
                 Piribedil 
                 Glyburide 
                 Clomiphene 
               
               
                 temozolomide 
                 Nordefrin 
                 Niacinamide 
               
               
                 Primidone 
                 Lobeline 
                 Ethylestrenol 
               
               
                 Tetrachlorodibenzodioxin 
                 Carnitine 
                 4-(4-fluorophenyl)-2-(4- 
               
               
                   
                   
                 hydroxyphenyl)-5-(4- 
               
               
                   
                   
                 pyridyl)imidazole 
               
               
                 Trichloroethylene 
                 Clonidine 
                 sevoflurane 
               
               
                 Immunoglobulin M 
                 motexafin gadolinium 
                 Pilocarpine 
               
               
                 Deoxycholic Acid 
                 dihydroquinghaosu 
                 piperaquine 
               
               
                 Amiodarone 
                 Ajmaline 
                 Amantadine 
               
               
                 picrotoxinin 
                 versipelostatin 
                 Mephentermine 
               
               
                 Calcitriol 
                 tracazolate 
                 gatifloxacin 
               
               
                 nilutamide 
                 securinine 
                 Azaguanine 
               
               
                 Ampicillin 
                 Epitestosterone 
                 Y 27632 
               
               
                 Nicergoline 
                 Isoproterenol 
                 16-ketoestradiol 
               
               
                 mycophenolate mofetil 
                 Aminocaproic Acids 
                 Epirubicin 
               
               
                 fulvestrant 
                 Immunoglobulins, 
                 Amphotericin B 
               
               
                   
                 Intravenous 
                   
               
               
                 Shiga Toxin 
                 Pemoline 
                 balsalazide 
               
               
                 Chlortetracycline 
                 Inosine Monophosphate 
                 Pimozide 
               
               
                 Betaxolol 
                 MF59 oil emulsion 
                 Nimodipine 
               
               
                 enterotoxin B, 
                 Nitrofurantoin 
                 pirinixic acid 
               
               
                 staphylococcal 
                   
                   
               
               
                 carvedilol 
                 Methazolamide 
                 Azacitidine 
               
               
                 Indomethacin 
                 Rotenone 
                 Rolipram 
               
               
                 Propranolol 
                 Albuterol 
                 Dichlorvos 
               
               
                 Sotalol 
                 enzastaurin 
                 Nitric Oxide 
               
               
                 N-Ac-CHAVC-NH2 
                 Tranylcypromine 
                 Cyclophosphamide 
               
               
                 Puromycin 
                 mono-(2-ethylhexyl)phthalate 
                 Neomycin 
               
               
                 Plicamycin 
                 phosphonoacetamide 
                 Ascorbic Acid 
               
               
                 bortezomib 
                 rofecoxib 
                 Mitomycin 
               
               
                 Chlorpromazine 
                 fluvastatin 
                 Clindamycin 
               
               
                 Palm itic Acid 
                 Deoxyglucose 
                 Kainic Acid 
               
               
                 Alpha-Amanitin 
                 Pergolide 
                 Oxymetazoline 
               
               
                 Vitamin E 
                 Mebendazole 
                 Ketoconazole 
               
               
                 Ciprofloxacin 
                 Clomipramine 
                 isoascorbic acid 
               
               
                 Ionomyin 
                 Thioguanine 
                 Cycloheximide 
               
               
                 Methyl Methanesulfonate 
                   
                   
               
            
           
           
               
            
               
                 F1. Molecules that upregulate ALDH4A1: 
               
            
           
           
               
               
               
            
               
                 Cyclopenthiazide  
                 Sulfadimethoxine 
                 Mephenesin 
               
               
                 Tiletamine 
                 Methotrimeprazine 
                 Trimethoprim 
               
               
                 tomatidine 
                 Pilocarpine 
                 citiolone 
               
               
                 Bisoprolol 
                 butacaine 
                 Glycopyrrolate 
               
               
                 Bufexamac 
                 chloropyramine 
                 pipenzolate 
               
               
                 Meclizine 
                 Zimeldine 
                 acetylleucine 
               
               
                 Albuterol 
                 amylocaine 
                 Methoxamine 
               
               
                 bacampicillin 
                 Etanidazole 
                 Riluzole 
               
               
                 Propranolol 
                 zaprinast 
                 telenzepine 
               
               
                 Azathioprine 
                 Cefixime 
                 Buspirone 
               
               
                 Bemegride 
                 4-acetylaminofluorene 
                 Sulfisoxazole 
               
               
                 ajmalicine 
                 pelargonic acid 
                 trimethobenzamide 
               
               
                 naringin 
                 sulfanilamide 
                 Oxyquinoline 
               
               
                 Dihydrostreptomycin 
                 triadimefon 
                 Hydralazine 
               
               
                 Sulfate 
                   
                   
               
               
                 oxaliplatin 
                 Norethindrone 
                 Chlorpheniramine 
               
               
                 Procaine 
                 Aclarubicin 
                 diflorasone diacetate 
               
               
                 Felodipine 
                 Tolmetin 
                 Sulfacetamide 
               
               
                 Amiloride 
                 Bromocriptine 
                 harman 
               
               
                 Propidium 
                 TO-901317 
                 benzothiazide 
               
               
                 Propylthiouracil 
                 Remoxipride 
                 efavirenz 
               
               
                 Cefazolin 
                 tridihexethyl 
                 Aristolochic Acids 
               
               
                 Dipyrone 
                 Moricizine 
                 Dihydrotestosterone 
               
               
                 1-(2-cyano-3,12- 
                 Etoposide 
                 Pargyline 
               
               
                 dioxooleana-1,9-dien-28-oyl)imidazole 
                   
                   
               
               
                 triptolide 
                 diisopropyl 
                 Ethylnitrosourea 
               
               
                   
                 methylphosphonate 
                   
               
               
                 Hymecromone 
                 Josamycin 
                 Methylnitrosourea 
               
               
                 clopidogrel 
                 Heptaminol 
                 Orphenadrine 
               
               
                 Tobramycin 
                 4-(N-methyl-N- 
                   
               
               
                   
                 nitrosamino)-1-(3-pyridyl)-1-butanone 
                 Nalidixic Acid 
               
               
                 eperisone 
                 Moxisylyte 
                 Ondansetron 
               
               
                 arcaine 
                 Spironolactone 
                 trichostatin A 
               
               
                 fenhexamid 
                 Doxorubicin 
                 monastrol 
               
               
                 Cyclopentolate 
                 clidinium 
                 Hydrocortisone 
               
               
                 artemisinine 
                 lorglumide 
                 Forskolin 
               
               
                 troglitazone 
                 8-(3-Chlorostyryl)-1,3,7-trimethylxanthine 
                 geldanamycin 
               
               
                 Cromolyn Sodium 
                 Selenomethionine 
                 2-nitrofluorene 
               
               
                 4,4′-diaminodiphenylmethane 
                 Glutamic Acid 
                 Vecuronium Bromide 
               
               
                 Guanfacine 
                 vorinostat 
                 Streptozocin 
               
               
                 Ethambutol 
                 Diethylnitrosamine 
                 Mephenytoin 
               
               
                 Azaperone 
                 diperodon 
                 Allantoin 
               
               
                 fomepizole 
                 Lamivudine 
                 Etilefrine 
               
               
                 Sulfasalazine 
                 VX 
                 oxolamine 
               
               
                 1-Methyl-3-isobutylxanthine 
                 Enalapril 
                 carbinoxamine 
               
               
                 Hydroxyzine 
                 Dilazep 
                 Cisplatin 
               
               
                 Glycocholic Acid 
                 Sulfameter 
                 clemizole 
               
               
                 apicidin 
                 ethotoin 
                 decitabine 
               
               
                 Levodopa 
                 isopyrin 
                 Aminopyrine 
               
               
                 Ticlopidine 
                 salicylamide 
                 enzastaurin 
               
               
                 chloroacetaldehyde 
                 butenafine 
                 fenspiride 
               
               
                 gefitinib 
                 Acetaminophen 
                 2-Acetylaminofluorene 
               
               
                 Kinetin 
                 Clarithromycin 
                 Practolol 
               
               
                 Cortisone 
                 Thiabendazole 
                 Nisoldipine 
               
               
                 Aflatoxin B1 
                 HC toxin 
                 discretamine 
               
               
                 Thiethylperazine 
                 Ketanserin 
                 3-nitropropionic acid 
               
               
                 tris(2,3- 
                 Mianserin 
                 Megestrol Acetate 
               
               
                 dibromopropyl)phosphate 
                   
                   
               
               
                 Aflatoxins 
                 Ultraviolet Rays 
                 vinorelbine 
               
               
                 pyrithyldione 
                 pirenperone 
                 Daunorubicin 
               
               
                 LBH589 
                 lapatinib 
                 asiaticoside 
               
               
                 Methacholine Chloride 
                 oxcarbazepine 
                 Ipratropium 
               
               
                 8-((4- 
                 Etidronic Acid 
                 Tin Fluorides 
               
               
                 chlorophenyl)thio)cyclic- 
                   
                   
               
               
                 3′,5-AMP 
                   
                   
               
               
                 Sulfamethazine 
                 rosiglitazone 
                 3,3′,4′,5- 
               
               
                   
                   
                 tetrachlorosalicylanilide 
               
               
                 amitraz 
                 romidepsin 
                 ascorbate-2-phosphate 
               
               
                 Corticosterone 
                 Pyrazinamide 
                 vinpocetine 
               
               
                 Ethamsylate 
                 Minocycline 
                 Ketamine 
               
               
                 Rolipram 
                 Ronidazole 
                 Curcumin 
               
               
                 Pinacidil 
                 Trichlormethiazide 
                 Mitomycin 
               
               
                 Luteolin 
                 lomefloxacin 
                 Dexamethasone 
               
               
                 piclamilast 
                 1,3-dichlorobenzene 
                 tranilast 
               
               
                 Carboplatin 
                 Glafenine 
                 diphemanil methylsulfate 
               
               
                 Sulfadiazine 
                 Testosterone 
                 Verapamil 
               
               
                 velnacrine 
                 Phorbol Esters 
                 Zalcitabine 
               
               
                 Zidovudine 
                 butamben 
                 Atrazine 
               
               
                 Ciprofloxacin 
                 Sumatriptan 
                 Tacrine 
               
               
                 fazarabine 
                 Cytochalasin B 
                 Carbimazole 
               
               
                 Botulinum Toxins, Type A 
                 Mustard Gas 
                 Carbamazepine 
               
               
                 Amphotericin B 
                 Dipyridamole 
                 Furosemide 
               
               
                 lead tetraacetate 
                 Mannitol 
                 cefepime 
               
               
                 Sorbitol 
                 letrozole 
                 Serotonin 
               
               
                 Tolbutamide 
                 Androsterone 
                 abacavir 
               
               
                 blebbistatin 
                 Cisapride 
                 Flunarizine 
               
               
                 Ritodrine 
                 Pentoxifylline 
                 scriptaid 
               
               
                 Camptothecin 
                 Bupropion 
                 picrotoxinin 
               
               
                 delsoline 
                 Hydroxyurea 
                 4-hydroxy-2-nonenal 
               
               
                 Valproic Acid 
                 Amoxapine 
                 Metaraminol 
               
               
                 Oxazepam 
                 Theophylline 
                 marimastat 
               
               
                 Citric Acid 
                 Podophyllotoxin 
                 Altretamine 
               
               
                 Mycophenolic Acid 
                 candesartan 
                 Paclitaxel 
               
               
                 Fenoprofen 
                 Gentamicins 
                 Vincristine 
               
               
                 versipelostatin 
                 erlotinib 
                 Nitric Oxide 
               
               
                 Phenoxybenzamine 
                 Prochlorperazine 
                 8-Bromo Cyclic Adenosine 
               
               
                   
                   
                 Monophosphate 
               
               
                 Enoxacin 
                 Chlortetracycline 
                 Choline 
               
               
                 Pregnenolone Carbonitrile 
                 Phenobarbital 
                 Chloramphenicol 
               
               
                 Vitamin E 
                 Clofibrate 
                 Busulfan 
               
               
                 sodium selenate 
                 Methotrexate 
                 Trifluoperazine 
               
               
                 Physostigmine 
                 Dimethyl Sulfoxide 
                 benazepril 
               
               
                 imatinib 
                 Galantamine 
                 Azauridine 
               
               
                 Diflunisal 
                 Fluorouracil 
                 4-(5-benzo(1,3)dioxol-5-yl- 
               
               
                   
                   
                 4-pyridin-2-yl-1H-imidazol- 
               
               
                   
                   
                 2-yl)benzamide 
               
               
                 Phenylephrine 
                 sodium arsenite 
                 Aspirin 
               
               
                 Neomycin 
                 Iproniazid 
                 Saquinavir 
               
               
                 Melphalan 
                 1-Methyl-4-phenyl-1,2,3,6- 
                 dasatinib 
               
               
                   
                 tetrahydropyridine 
                   
               
               
                 Ascorbic Acid 
                 Nocodazole 
                 Soman 
               
               
                 U 0126 
                 HI 6 
                 Captopril 
               
               
                 Ionomyin 
                 Chitosan 
                 Digoxin 
               
               
                 Dactinomycin 
                 Cycloheximide 
                 Amitrole 
               
               
                 Nicotine 
                 Chlorpyrifos 
                 Dichlorvos 
               
               
                 Cyclophosphamide 
                 Azacitidine 
                   
               
            
           
           
               
            
               
                 F2. Molecules that downregulate ALDH4A1: 
               
            
           
           
               
               
               
            
               
                 spiradoline 
                 alfuzosin 
                 Buthionine Sulfoximine 
               
               
                 hydroxytamoxifen 
                 Oxolinic Acid 
                 Nialamide 
               
               
                 tianeptine 
                 am ineptin 
                 homosalate 
               
               
                 9-(2-hydroxy-3- 
                 Vinblastine 
                 Lidoflazine 
               
               
                 nonyl)adenine 
                   
                   
               
               
                 Gliclazide 
                 althiazide 
                 Isosorbide 
               
               
                 Isotretinoin 
                 sunitinib 
                 enrofloxacin 
               
               
                 telmisartan 
                 Cefuroxime 
                 doxofylline 
               
               
                 Estradiol 
                 Quinidine 
                 Ursodeoxycholic Acid 
               
               
                 piretanide 
                 ubiquinol 
                 daidzein 
               
               
                 Aminosalicylic Acid 
                 Colchicine 
                 Genistein 
               
               
                 fulvestrant 
                 Imipramine 
                 Probenecid 
               
               
                 Amantadine 
                 desloratadine 
                 Pheniramine 
               
               
                 Fluoxetine 
                 Disopyramide 
                 Ecdysterone 
               
               
                 Simvastatin 
                 Methylergonovine 
                 ebselen 
               
               
                 betulinic acid 
                 repaglinide 
                 Anti-Retroviral Agents 
               
               
                 naringenin 
                 Reserpine 
                 nickel chloride 
               
               
                 Lithocholic Acid 
                 N-acetylsphingosine 
                 bisphenol A 
               
               
                 vinylidene chloride 
                 valdecoxib 
                 Tetracycline 
               
               
                 beta-Naphthoflavone 
                 Cinoxacin 
                 bendazolic acid 
               
               
                 Diclofenac 
                 Cytochalasin D 
                 Ethinyl Estradiol 
               
               
                 venlafaxine 
                 Lovastatin 
                 Mestranol 
               
               
                 moroxydine 
                 Cephapirin 
                 alachlor 
               
               
                 Chloroquine 
                 norethindrone acetate 
                 Erythromycin 
               
               
                 Sparteine 
                 Labetalol 
                 2-dichlorobenzene 
               
               
                 Clonidine 
                 lacidipine 
                 Indomethacin 
               
               
                 Gold 
                 Sulindac 
                 Etodolac 
               
               
                 Clemastine 
                 4-hydroxytamoxifen 
                 Diethylstilbestrol 
               
               
                 Ranitidine 
                 Oxytetracycline 
                 Zinc Sulfate 
               
               
                 Natamycin 
                 etofylline 
                 isopropamide iodide 
               
               
                 olanzapine 
                 Estriol 
                 triflusal 
               
               
                 Canrenoate Potassium 
                 Methapyrilene 
                 Lobeline 
               
               
                 Alprazolam 
                 Pergolide 
                 pioglitazone 
               
               
                 Ethionamide 
                 hydrastinine 
                 Clozapine 
               
               
                 Pravastatin 
                 calycanthine 
                 N-(2-cyclohexyloxy-4- 
               
               
                   
                   
                 nitrophenyl)methanesulfonamide 
               
               
                 Sertraline 
                 Naproxen 
                 Digitoxin 
               
               
                 Carbon Tetrachloride 
                 estradiol 3-benzoate 
                 bicalutamide 
               
               
                 Roflumilast 
                 suxibuzone 
                 acetorphan 
               
               
                 Viomycin 
                 Dichlorphenamide 
                 aluminum sulfate 
               
               
                 Acetohexamide 
                 carvedilol 
                 Vincamine 
               
               
                 Thioacetamide 
                 Metoprolol 
                 Raloxifene 
               
               
                 Doxepin 
                 Promethazine 
                 geraniol 
               
               
                 Niridazole 
                 Nafenopin 
                 Antigen-Antibody Complex 
               
               
                 dexchlorpheniramine 
                 Nitrendipine 
                 Isoflurophate 
               
               
                 Amitriptyline 
                 Miconazole 
                 Biotin 
               
               
                 Betamethasone 
                 Glycine 
                 Phenelzine 
               
               
                 Sotalol 
                 Trihexyphenidyl 
                 Tacrolimus 
               
               
                 famciclovir 
                 Isoniazid 
                 4-dichlorobenzene 
               
               
                 Cimetidine 
                 Bumetanide 
                 Dinitrophenols 
               
               
                 benziodarone 
                 Paroxetine 
                 Fluocinolone Acetonide 
               
               
                 Dimethylformamide 
                 sulfathiazole 
                 Danazol 
               
               
                 Rifampin 
                 Phenindione 
                 boldine 
               
               
                 Pirenzepine 
                 Fluphenazine 
                 Naloxone 
               
               
                 Ethionine 
                 sorafenib 
                 Pemoline 
               
               
                 Amiodarone 
                 Capsaicin 
                 Disulfiram 
               
               
                 motexafin gadolinium 
                 Hydrogel 
                 oxfendazole 
               
               
                 Antimycin A 
                 prochloraz 
                 sildenafil 
               
               
                 ipriflavone 
                 Deoxycholic Acid 
                 N-Methylscopolamine 
               
               
                 gabapentin 
                 dexibuprofen 
                 Cyclosporine 
               
               
                 Brefeldin A 
                 Secobarbital 
                 anastrozole 
               
               
                 rabeprazole 
                 Meclofenamic Acid 
                 Diphenhydramine 
               
               
                 oxybutynin 
                 Phenytoin 
                 atorvastatin 
               
               
                 canadine 
                 biphenylylacetic acid 
                 Dobutamine 
               
               
                 pantoprazole 
                 Diltiazem 
                 Risperidone 
               
               
                 Astemizole 
                 Methylcholanthrene 
                 aceclofenac 
               
               
                 genipin 
                 Rotenone 
                 idebenone 
               
               
                 cobaltous chloride 
                 Diazinon 
                 titanium dioxide 
               
               
                 Estrogens 
                 deferiprone 
                 alpha-Amino-3-hydroxy-5- 
               
               
                   
                   
                 methyl-4-isoxazolepropionic 
               
               
                   
                   
                 Acid 
               
               
                 Sirolimus 
                 Ifosfamide 
                 1,1,1 -trichloroethane 
               
               
                 halofuginone 
                 pristane 
                 Chloroform 
               
               
                 sulforafan 
                 Flutamide 
                 phenylhydrazine 
               
               
                 5′-methylthioadenosine 
                 lysophosphatidic acid 
                 Ecdysone 
               
               
                 quetiapine 
                 Acyclovir 
                 Finasteride 
               
               
                 epoxomicin 
                 Indapamide 
                 Nalbuphine 
               
               
                 Gemfibrozil 
                 Azlocillin 
                 beta-cyclodextrin-benzaldehyde 
               
               
                 modafinil 
                 rifapentine 
                 4-octylphenol 
               
               
                 Nortriptyline 
                 Ofloxacin 
                 Dantrolene 
               
               
                 efalizumab 
                 Diethylhexyl Phthalate 
                 Poly I-C 
               
               
                 tazobactam 
                 sparfloxacin 
                 nimesulide 
               
               
                 Citalopram 
                 Phentolamine 
                 4-nonylphenol 
               
               
                 Bacitracin 
                 Tiapamil Hydrochloride 
                 Nimodipine 
               
               
                 Bezafibrate 
                 Chlorpromazine 
                 Metyrapone 
               
               
                 benfluorex 
                 Chlormadinone Acetate 
                 Coumaphos 
               
               
                 Potassium Dichromate 
                 6-Mercaptopurine 
                 Clomipramine 
               
               
                 leflunomide 
                 Thioridazine 
                 Chlorambucil 
               
               
                 cyanoginosin LR 
                 Thapsigargin 
                 2-(4-morpholinyl)-8-phenyl-4H- 
               
               
                   
                   
                 1-benzopyran-4-one 
               
               
                 Clonazepam 
                 meloxicam 
                 2-methoxyestradiol 
               
               
                 cilostazol 
                 Quinacrine 
                 Ibuprofen 
               
               
                 fluvastatin 
                 phenethyl isothiocyanate 
                 chlorcyclizine 
               
               
                 Vanadates 
                 lactacystin 
                 Ketoconazole 
               
               
                 Itraconazole 
                 Econazole 
                 Isoproterenol 
               
               
                 Tocainide 
                 benzamil 
                 Floxuridine 
               
               
                 Thioguanine 
                 Tranexamic Acid 
                 temsirolimus 
               
               
                 Concanavalin A 
                 Aminoglutethimide 
                 Deoxyglucose 
               
               
                 Clotrimazole 
                 Terazosin 
                 resveratrol 
               
               
                 SB 203580 
                 Nadolol 
                 cerivastatin 
               
               
                 Fluconazole 
                 Tinidazole 
                 Promazine 
               
               
                 Allopurinol 
                 lansoprazole 
                 Perhexiline 
               
               
                 linezolid 
                 Pentylenetetrazole 
                 ONO 2235 
               
               
                 Deferoxamine 
                 Loratadine 
                 bortezomib 
               
               
                 ferulic acid 
                 Sulpiride 
                 Tropicamide 
               
               
                 Cytarabine 
                 Baclofen 
                 Nifedipine 
               
               
                 acadesine 
                 Fluvoxamine 
                 Melatonin 
               
               
                 Haloperidol 
                 Methazolamide 
                 Streptomycin 
               
               
                 Omeprazole 
                 Clindamycin 
                 terbinafine 
               
               
                 Terfenadine 
                 Diazepam 
                 Ramipril 
               
               
                 Caffeine 
                 Cinnarizine 
                 Calcitriol 
               
               
                 Quercetin 
                 Granisetron 
                 Phenylalanine 
               
               
                 valsartan 
                 Dicyclomine 
                 Ketorolac 
               
               
                 Lisinopril 
                 Cyproheptadine 
                 Nevirapine 
               
               
                 Pyrogallol 
                 Piroxicam 
                 Stavudine 
               
               
                 rofecoxib 
                 benzyloxycarbonylleucyl- 
                 zileuton 
               
               
                   
                 leucyl-leucine aldehyde 
                   
               
               
                 gemcitabine 
                 irinotecan 
                 pirinixic acid 
               
               
                 isoascorbic acid 
                 Oxymetazoline 
                 Papaverine 
               
               
                 Acetazolamide 
                 Hydrochlorothiazide 
                 Lomustine 
               
               
                 Carmustine 
                 Clofibric Acid 
                 Amphetamine 
               
            
           
           
               
            
               
                 G1. Molecules that upregulate SLC36A1: 
               
            
           
           
               
               
               
            
               
                 pridinol 
                 Talampicillin 
                 N(1)-methyl-2-lysergic 
               
               
                   
                   
                 acid diethylamide 
               
               
                 Piperacillin 
                 sertaconazole 
                 Theobromine 
               
               
                 isopyrin 
                 Sulfaquinoxaline 
                 adrenosterone 
               
               
                 iturelix 
                 troglitazone 
                 Salicylates 
               
               
                 CpG ODN 2216 
                 Grape Seed 
                 pioglitazone 
               
               
                   
                 Proanthocyanidins 
                   
               
               
                 4-hydroxy-2-nonenal 
                 Insulin 
                 tripterine 
               
               
                 lenalidomide 
                 Erythromycin 
                 Pentolinium Tartrate 
               
               
                   
                 Ethylsuccinate 
                   
               
               
                 Aclarubicin 
                 SC 514 
                 cryptoxanthin 
               
               
                 tridihexethyl 
                 Cromolyn Sodium 
                 Mycotoxins 
               
               
                 Endotoxins 
                 Glafenine 
                 SB 203580 
               
               
                 Yellow Fever Vaccine 
                 Vitamin E 
                 withaferin A 
               
               
                 Botulinum Toxins, Type A 
                 lorglumide 
                 flumequine 
               
               
                 Propanil 
                 rosiglitazone 
                 Albuterol 
               
               
                 CD 437 
                 Fluorometholone 
                 1,3-dichlorobenzene 
               
               
                 MF59 oil emulsion 
                 Inosine Monophosphate 
                 Trimethoprim 
               
               
                 Methoxamine 
                 romidepsin 
                 Didanosine 
               
               
                 diphemanil methylsulfate 
                 sodium chlorate 
                 15-deoxy-delta(12,14)- 
               
               
                   
                   
                 prostaglandin J2 
               
               
                 gefitinib 
                 Trimeprazine 
                 fazarabine 
               
               
                 Valproic Acid 
                 Tetrachloroethylene 
                 1,5-naphthalenediamine 
               
               
                 decitabine 
                 procyanidin 
                 monobenzone 
               
               
                 indole-3-carbinol 
                 Mexiletine 
                 direct black 3 
               
               
                 Biotin 
                 Metribolone 
                 mefexamide 
               
               
                 trichostatin A 
                 Quercetin 
                 GW 3965 
               
               
                 2-dichlorobenzene 
                 4-dichlorobenzene 
                 alginic acid 
               
               
                 Roxarsone 
                 rilmenidine 
                 Nefopam 
               
               
                 Fludrocortisone 
                 lapatinib 
                 Dexamethasone 
               
               
                 midecamycin 
                 Hycanthone 
                 Monocrotaline 
               
               
                 caffeic acid 
                 zaprinast 
                 Dihydrotestosterone 
               
               
                 blebbistatin 
                 monastrol 
                 enzastaurin 
               
               
                 Calcitriol 
                 pristane 
                 vesamicol 
               
               
                 geldanamycin 
                 Pempidine 
                 cyanopindolol 
               
               
                 Trifluoperazine 
                 Cytochalasin B 
                 Lincomycin 
               
               
                 fragment C, human serum albumin 
                 LPS 9 
                 Thioridazine 
               
               
                 Dimethylnitrosamine 
                 Epirizole 
                 Cefuroxime 
               
               
                 Perhexiline 
                 N-nitrosomorpholine 
                 Octopamine 
               
               
                 Dichlororibofuranosylbenzimidazole 
                 Paclitaxel 
                 Metoclopramide 
               
               
                 Bleomycin 
                 Acetylcysteine 
                 Vincristine 
               
               
                 ajmalicine 
                 Gonadotropins 
                 Simazine 
               
               
                 Pipemidic Acid 
                 homatropine 
                 daboiatoxin 
               
               
                 lomefloxacin 
                 Rifabutin 
                 Amiloride 
               
               
                 Heparin 
                 Chlorpromazine 
                 celecoxib 
               
               
                 homochlorocyclizine 
                 quintozene 
                 Lynestrenol 
               
               
                 Carcinogens 
                 Ascorbic Acid 
                 Immunoglobulin M 
               
               
                 Carbachol 
                 Oxyquinoline 
                 Doxepin 
               
               
                 Malathion 
                 vorinostat 
                 Rolipram 
               
               
                 kavain 
                 Vitamin K 3 
                 16-ketoestradiol 
               
               
                 4-amino-6-hydrazino-7-beta-D- 
                 Apomorphine 
                 Phenoxybenzamine 
               
               
                 ribofuranosyl-7H-pyrrolo(2,3-d)- 
                   
                   
               
               
                 pyrimidine-5-carboxamide 
                   
                   
               
               
                 imatinib 
                 Dinoprost 
                 sapphyrin 
               
               
                 benzyloxycarbonylleucyl-leucyl- 
                 Doxorubicin 
                 Disulfiram 
               
               
                 leucine aldehyde 
                   
                   
               
               
                 sulfathiazole 
                 triadimefon 
                 LBH589 
               
               
                 Diltiazem 
                 Hydroxyzine 
                 Aztreonam 
               
               
                 adalimumab 
                 Benzo(a)pyrene 
                 heliotrine 
               
               
                 resveratrol 
                 Methylnitrosourea 
                 rituximab 
               
               
                 Ethacrynic Acid 
                 Propylthiouracil 
                 Diazinon 
               
               
                 fluticasone 
                 Tetradecanoylphorbol Acetate 
                 Methotrexate 
               
               
                 Sulfasalazine 
                 Clomipramine 
                 fulvestrant 
               
               
                 copolymer 1 
                 Piperonyl Butoxide 
                 Levonorgestrel 
               
               
                 4-hydroxytamoxifen 
                 bromodichloromethane 
                 dasatinib 
               
               
                 Acetaminophen 
                 Tretinoin 
                 Azathioprine 
               
               
                 Hemin 
                 Chorionic Gonadotropin 
                 Labetalol 
               
               
                 Fluoxetine 
                 Nifedipine 
                 Iproniazid 
               
               
                 testosterone 
                 17 beta- 
                   
               
               
                 Aflatoxin B1 
                 Phenacetin 
                 cypionate 
               
               
                 Ergocalciferols 
                 HI 6 
                 Topotecan 
               
               
                 irinotecan 
                 Mycophenolic Acid 
                 Methyl Methanesulfonate 
               
               
                 colforsin 
                 bortezomib 
                 Hydrogen Peroxide 
               
               
                 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl- 
                 methylatropine 
                 Nitric Oxide 
               
               
                 1H-im idazol-2-yl)benzamide 
                   
                   
               
               
                 pantoprazole 
                 Pregnenolone Carbonitrile 
                 Immunotoxins 
               
               
                 sulforafan 
                 Ethosuximide 
                 Promazine 
               
               
                 Methylene Chloride 
                 Colchicine 
                 Nortriptyline 
               
               
                 Particulate Matter 
                 Medroxyprogesterone Acetate 
                 torsemide 
               
               
                 rabeprazole 
                 Risperidone 
                 Nocodazole 
               
               
                 Puromycin 
                 ochratoxin A 
                 Tacrine 
               
               
                 Penicillamine 
                 Enalapril 
                 Atropine 
               
               
                 Caffeine 
                 Indomethacin 
                 Camptothecin 
               
               
                 fluvastatin 
                 sodium arsenite 
                 Diazepam 
               
               
                 Fluorouracil 
                 Clotrimazole 
                 Amitriptyline 
               
               
                 Azacitidine 
                   
                   
               
            
           
           
               
            
               
                 G2. Molecules that downregulate SLC36A1: 
               
            
           
           
               
               
               
            
               
                 carbetapentane 
                 Methoxsalen 
                 lonidamine 
               
               
                 Alpha-Amanitin 
                 genipin 
                 quinethazone 
               
               
                 Betaxolol 
                 clemizole 
                 Bisoprolol 
               
               
                 verteporfin 
                 Prenylamine 
                 Nafronyl 
               
               
                 fenspiride 
                 ciclopirox 
                 ascorbate-2-phosphate 
               
               
                 Indapamide 
                 GW 501516 
                 Cholera Toxin 
               
               
                 Dihydroergotamine 
                 Methamphetamine 
                 parbendazole 
               
               
                 harmol 
                 Trioxsalen 
                 BCG Vaccine 
               
               
                 Eugenol 
                 Benserazide 
                 Apigenin 
               
               
                 moxonidine 
                 Immunoglobulin G 
                 naphthalene 
               
               
                 enterotoxin I, staphylococcal 
                 Bethanechol 
                 Curcumin 
               
               
                 Mesalamine 
                 Famotidine 
                 Growth Hormone 
               
               
                 Santonin 
                 mebhydroline 
                 Cisapride 
               
               
                 Coumarins 
                 Platelet Activating Factor 
                 Mannitol 
               
               
                 Tetrachlorodibenzodioxin 
                 2-nitrofluorene 
                 Ambroxol 
               
               
                 Aflatoxins 
                 Ganciclovir 
                 hydroxyachillin 
               
               
                 Ethambutol 
                 MK 0591 
                 Tolmetin 
               
               
                 flunixin 
                 Acetohexamide 
                 phthalylsulfathiazole 
               
               
                 Thapsigargin 
                 Tunicamycin 
                 Sulfadimethoxine 
               
               
                 rauwolscine-OHPC 
                 lobelanidine 
                 acidocin CH5, 
               
               
                   
                   
                 
                   Lactobacillus acidophilus 
                 
               
               
                 infliximab 
                 Glipizide 
                 Concanavalin A 
               
               
                 chelidonine 
                 Clorgyline 
                 Antigen-Antibody Complex 
               
               
                 2,2′-(hydroxynitrosohydrazono)bis- 
                 Practolol 
                 Azoxymethane 
               
               
                 ethanamine 
                   
                   
               
               
                 Oxytocin 
                 skimmianine 
                 Ethisterone 
               
               
                 shikonin 
                 Minocycline 
                 1-Methyl-3-isobutylxanthine 
               
               
                 Flutamide 
                 Primaquine 
                 Mafenide 
               
               
                 Diethylhexyl Phthalate 
                 Acepromazine 
                 Cyclophosphamide 
               
               
                 Harmine 
                 Protoveratrines 
                 solasodine 
               
               
                 Dinoprostone 
                 17-(allylamino)-17- 
                 Prednisolone 
               
               
                   
                 demethoxygeldanamycin 
                   
               
               
                 Corticosterone 
                 Ceftazidime 
                 CPG-oligonucleotide 
               
               
                 Palmitic Acid 
                 Selenomethionine 
                 Cholecalciferol 
               
               
                 halofuginone 
                 Beclomethasone 
                 beta-cyclodextrin-benzaldehyde 
               
               
                 amlexanox 
                 trilinolein 
                 amylocaine 
               
               
                 Staurosporine 
                 Deoxycholic Acid 
                 Gemfibrozil 
               
               
                 Atrazine 
                 Isoniazid 
                 sangivamycin 
               
               
                 triptolide 
                 Enterotoxins 
                 Rifampin 
               
               
                 titanium dioxide 
                 ellipticine 
                 AICA ribonucleotide 
               
               
                 nifuroxazide 
                 Estriol 
                 Paroxetine 
               
               
                 Dextran Sulfate 
                 Pyrazinamide 
                 Procainamide 
               
               
                 Dilazep 
                 Imipramine 
                 TO-901317 
               
               
                 Clonidine 
                 salsolidine 
                 Estradiol 
               
               
                 6-azathymine 
                 4-acetylaminofluorene 
                 Chlorprothixene 
               
               
                 Niclosamide 
                 Methyltestosterone 
                 Ethanol 
               
               
                 8-Bromo Cyclic Adenosine 
                 Propofol 
                 Poly I-C 
               
               
                 Monophosphate 
                   
                   
               
               
                 Immunoglobulins, 
                 Intravenous Hydralazine 
                 sanguinarine 
               
               
                 Dextromethorphan 
                 Piracetam 
                 Acrolein 
               
               
                 Cyclosporine 
                 Vincamine 
                 Lovastatin 
               
               
                 Cycloheximide 
                 ciprofibrate 
                 Luteinizing Hormone 
               
               
                 Penicillin G 
                 vinclozolin 
                 emtricitabine 
               
               
                 bis(tri-n-butyltin)oxide 
                 Benzbromarone 
                 Folic Acid 
               
               
                 bicalutamide 
                 Pyrogens 
                 Bicuculline 
               
               
                 Doxazosin 
                 Deoxyglucose 
                 docetaxel 
               
               
                 R 848 
                 Phenobarbital 
                 tenofovir 
               
               
                 arsenic trioxide 
                 Luteolin 
                 Pentylenetetrazole 
               
               
                 Mitoxantrone 
                 Norfloxacin 
                 poly ICLC 
               
               
                 lead acetate 
                 Diethylstilbestrol 
                 cobaltous chloride 
               
               
                 Hydroxyurea 
                 fasudil 
                 piclamilast 
               
               
                 dibenzazepine 
                 Sirolimus 
                 X-Rays 
               
               
                 2-(4-morpholinyl)-8-phenyl- 
                 enterotoxin B, 
                 trovafloxacin 
               
               
                 4H-1-benzopyran-4-one 
                 staphylococcal 
                   
               
               
                 Cisplatin 
                 Cytokines 
                 Dinitrofluorobenzene 
               
               
                 Cephalothin 
                 quelamycin 
                 Epitestosterone 
               
               
                 Albendazole 
                 Anti-Retroviral Agents 
                 salicylamide 
               
               
                 Niacinamide 
                 Chlormadinone Acetate 
                 Guanethidine 
               
               
                 Amoxicillin 
                 versipelostatin 
                 Ionomyin 
               
               
                 Metform in 
                 Papaverine 
                 mycophenolate mofetil 
               
               
                 pirinixic acid 
                 balsalazide 
                 Bezafibrate 
               
               
                 Trimethadione 
                 Sulpiride 
                 Haloperidol 
               
               
                 Forskolin 
                 Ticlopidine 
                 Ultraviolet Rays 
               
               
                 Tacrolimus 
                 Methapyrilene 
                 Chloroform 
               
               
                 Nicotine 
                 Procarbazine 
                 Dactinomycin 
               
               
                 Phytohemagglutinins 
                 bisphenol A 
                 erlotinib 
               
               
                 nimesulide 
                 Cytarabine 
                 Carmustine 
               
               
                 Naproxen 
                 Diclofenac 
                 Aspirin 
               
               
                 Clofibrate 
                   
                   
               
            
           
           
               
            
               
                 H1. Molecules that upregulate SLC36A2: 
               
            
           
           
               
               
               
            
               
                 Ascorbic Acid 
                 Teriparatide 
                 aluminum sulfate 
               
               
                 Gonadotropins 
                 Bismuth 
                 Salicylates 
               
               
                 acodazole 
                 Enterotoxins 
                 rosiglitazone 
               
               
                 beta-Naphthoflavone 
                 Tretinoin 
                 Chorionic Gonadotropin 
               
               
                 Azacitidine 
                 Hyaluronic Acid 
                 4-(5-benzo(1,3)dioxol-5-yl- 
               
               
                   
                   
                 4-pyridin-2-yl-1H-imidazol- 
               
               
                   
                   
                 2-yl)benzamide 
               
               
                 Cycloheximide 
                 Metronidazole 
                 bisphenol A 
               
               
                 Heparin 
                 MF59 oil emulsion 
                 pioglitazone 
               
               
                 Tetracycline 
                 Phenobarbital 
                 blebbistatin 
               
               
                 Niacinamide 
                 CPG-oligonucleotide 
                 Trenbolone Acetate, 
               
               
                   
                   
                 (17beta)-isomer 
               
               
                 4-hydroxytamoxifen 
                 Dimethylnitrosamine 
                 Hemin 
               
               
                 Insulin 
                 Azoxymethane 
                 imatinib 
               
               
                 Quercetin 
                 Doxorubicin 
                 Immunotoxins 
               
               
                 Clomipramine 
                 Dinoprostone 
                 Sulindac 
               
               
                 gefitinib 
                 Tetrachlorodibenzodioxin 
                 Genistein 
               
               
                 Indomethacin 
                 Dactinomycin 
                 bortezomib 
               
               
                 Diethylstilbestrol 
                 Methotrexate 
                 Sirolimus 
               
            
           
           
               
            
               
                 H2. Molecules that downregulate SLC36A2: 
               
            
           
           
               
               
               
            
               
                 ubiquinol 
                 BRL 37344 
                 Bleomycin 
               
               
                 Trichloroepoxypropane 
                 ranolazine 
                 Nandrolone 
               
               
                 chlorinated dibenzofurans 
                 pristane 
                 withaferin A 
               
               
                 Berberine 
                 lysophosphatidic acid 
                 Ouabain 
               
               
                 Melphalan 
                 1,5-naphthalenediamine 
                 vanadium pentoxide 
               
               
                 Ozone 
                 quintozene 
                 resveratrol 
               
               
                 Chitosan 
                 R 848 
                 Dinitrofluorobenzene 
               
               
                 Anti-Retroviral Agents 
                 Estradiol 
                 dexibuprofen 
               
               
                 sulforafan 
                 Cytokines 
                 enterotoxin B, 
               
               
                   
                   
                 staphylococcal 
               
               
                 Megestrol Acetate 
                 Isoproterenol 
                 acidocin CH5,  Lactobacillus   
               
               
                   
                   
                 
                   acidophilus 
                 
               
               
                 Hydralazine 
                 Antigen-Antibody Complex 
                 Betamethasone 
               
               
                 Growth Hormone 
                 Vitamin E 
                 Dexamethasone 
               
               
                 Methylene Chloride 
                 Fluoxetine 
                 Estriol 
               
               
                 Cyclophosphamide 
                 Phenytoin 
                 Captopril 
               
               
                 Progesterone 
                 Kainic Acid 
                 Tetradecanoylphorbol 
               
               
                   
                   
                 Acetate 
               
               
                 Calcitriol 
                 Colchicine 
                 Valproic Acid 
               
               
                 Bezafibrate 
                 Cisplatin 
                   
               
            
           
           
               
            
               
                 I1. Molecules that upregulate SLC36A4: 
               
            
           
           
               
               
               
            
               
                 Glutamic Acid 
                 Phytohemagglutinins 
                 Cymarine 
               
               
                 daidzein 
                 Brefeldin A 
                 Caffeine 
               
               
                 2,2-bis(bromomethyl)-1,3- 
                 Ergocalciferols 
                 Patulin 
               
               
                 propanediol 
                   
                   
               
               
                 Deferoxamine 
                 Cefuroxime 
                 1-ethyl-2- 
               
               
                   
                   
                 benzimidazolinone 
               
               
                 Dihydrotestosterone 
                 Methylnitrosourea 
                 Tretinoin 
               
               
                 8-Bromo Cyclic Adenosine 
                 25-hydroxycholesterol 
                 Lithium 
               
               
                 Monophosphate 
                   
                   
               
               
                 Ecdysone 
                 bisphenol A 
                 Eugenol 
               
               
                 Medroxyprogesterone 
                 Acetate R 848 
                 fragment C, human 
               
               
                   
                   
                 serum albumin 
               
               
                 Genistein 
                 Malathion 
                 alpha-Tocopherol 
               
               
                 Potassium Dichromate 
                 N-Methylaspartate 
                 infliximab 
               
               
                 bafilomycin A 
                 6-bromoindirubin-3′-oxime 
                 Estradiol 
               
               
                 4-biphenylamine 
                 tenofovir 
                 Dinoprostone 
               
               
                 2,2′-(hydroxynitrosohydrazono)bis- 
                 DDT 
                 Enterotoxins 
               
               
                 ethanamine 
                   
                   
               
               
                 Diethylstilbestrol 
                 benzyloxycarbonylleucyl- 
                 interferon alfa-2b 
               
               
                   
                 leucyl-leucine aldehyde 
                   
               
               
                 gamma-Tocopherol 
                 cyanoginosin LR 
                 Glycerol 
               
               
                 Folic Acid 
                 Azacitidine 
                 vorinostat 
               
               
                 sorafenib 
                 procyanidin 
                 Progesterone 
               
               
                 Tunicamycin 
                 Pregnenolone Carbonitrile 
                 Cardiotoxins 
               
               
                 Dexamethasone 
                 Calcitriol 
                 Nifedipine 
               
               
                 Captopril 
                 Piperonyl Butoxide 
                 Plicamycin 
               
               
                 Acetaminophen 
                 indole-3-carbinol 
                 Levonorgestrel 
               
               
                 Vincristine 
                 Cholecalciferol 
                 Thapsigargin 
               
               
                 Ranitidine 
                 pristane 
                 quintozene 
               
               
                 Theophylline 
                 triadimefon 
                 Doxepin 
               
               
                 Choline 
                 2-(4-morpholinyl)-8-phenyl- 
                 Azoxymethane 
               
               
                   
                 4H-1-benzopyran-4-one 
                   
               
               
                 Y 27632 
                 rosiglitazone 
                 letrozole 
               
               
                 Enalapril 
                 Dactinomycin 
                 Acetylcysteine 
               
               
                 Cisplatin 
                 Phosphorylcholine 
                 cobaltous chloride 
               
               
                 Aflatoxin B1 
                 Propylthiouracil 
                 colforsin 
               
               
                 Cadmium 
                 Insulin 
                 Ecdysterone 
               
               
                 lead acetate 
                 4-hydroxytamoxifen 
                 Paclitaxel 
               
               
                 Promethazine 
                 Chlorpromazine 
                 Cam ptothecin 
               
               
                 Ionomyin 
                 Amitrole 
                 Ethanol 
               
               
                 Isoniazid 
                 sodium arsenite 
                 Pyrazinamide 
               
               
                 Chlorambucil 
                 Ultraviolet Rays 
                 4-(5-benzo(1,3)dioxol-5- 
               
               
                   
                   
                 yl-4-pyridin-2-yl-1H- 
               
               
                   
                   
                 imidazol-2-yl)benzamide 
               
               
                 bortezomib 
                 imatinib 
                 gefitinib 
               
               
                 Ethinyl Estradiol 
                 Vitamin K 3 
                 Hydroxyurea 
               
            
           
           
               
            
               
                 I2. Molecules that downregulate SLC36A4: 
               
            
           
           
               
               
               
            
               
                 chromium hexavalention 
                 3-deazaneplanocin 
                 1-(2-cyano-3,12- 
               
               
                   
                   
                 dioxooleana-1,9-dien-28- 
               
               
                   
                   
                 oyl) imidazole 
               
               
                 Metformin 
                 Inosine Monophosphate 
                 Am 580 
               
               
                 cryptoxanthin 
                 lapatinib 
                 1-(5-lsoquinolinesulfonyl)- 
               
               
                   
                   
                 2-Methylpiperazine 
               
               
                 SC 514 
                 4-cyclododecyl-2,6- 
                 4-dichlorobenzene 
               
               
                   
                 dimethylmorpholine acetate 
                   
               
               
                 Histidinol 
                 Aphidicolin 
                 N-(2-aminophenyl)-4-(N- 
               
               
                   
                   
                 (pyridin-3- 
               
               
                   
                   
                 ylmethoxycarbonyl)aminomethyl) 
               
               
                   
                   
                 benzamide 
               
               
                 trichostatin A 
                 Hemin 
                 blebbistatin 
               
               
                 Sirolimus 
                 Quercetin 
                 N-nitrosomorpholine 
               
               
                 Azithromycin 
                 decitabine 
                 Methylene Chloride 
               
               
                 Cycloheximide 
                 TO-901317 
                 Poly I-C 
               
               
                 lactacystin 
                 Polychlorinated Biphenyls 
                 Benzo(a)pyrene 
               
               
                 fulvestrant 
                 romidepsin 
                 Diethylhexyl Phthalate 
               
               
                 bicalutamide 
                 Dinitrofluorobenzene 
                 enzastaurin 
               
               
                 monastrol 
                 fluticasone 
                 salmeterol 
               
               
                 Doxycycline 
                 Bucladesine 
                 2-dichlorobenzene 
               
               
                 Calcium 
                 2-(1H-indazol-4-yl)-6-(4- 
                 Calcium Chloride 
               
               
                   
                 methanesulfonylpiperazin-1- 
                   
               
               
                   
                 ylmethyl)-4-morpholin-4- 
                   
               
               
                   
                 ylthieno(3,2-d)pyrimidine 
                   
               
               
                 halofuginone 
                 4-acetylaminofluorene 
                 CPG-oligonucleotide 
               
               
                 geldanamycin 
                 Cyproterone Acetate 
                 Phenobarbital 
               
               
                 withaferin A 
                 Hydrogen Peroxide 
                 Raloxifene 
               
               
                 bexarotene 
                 Dimethyl Sulfoxide 
                 Curcum in 
               
               
                 atorvastatin 
                 Doxorubicin 
                 erlotinib 
               
               
                 dihydroquinghaosu 
                 piperaquine 
                 fasudil 
               
               
                 sapphyrin 
                 BCG Vaccine 
                 acidocin CH5,  Lactobacillus   
               
               
                   
                   
                 
                   acidophilus 
                 
               
               
                 Antigen-Antibody Complex 
                 Lactic Acid 
                 Vitamin E 
               
               
                 bromobenzene 
                 troglitazone 
                 Zinc Oxide 
               
               
                 Tacrine 
                 phorbolol myristate acetate 
                 pioglitazone 
               
               
                 Ribavirin 
                 Papaverine 
                 Bleomycin 
               
               
                 LBH589 
                 X-Rays 
                 Ascorbic Acid 
               
               
                 Cyclosporine 
                 Daunorubicin 
                 bevacizumab 
               
               
                 Pyrogens 
                 beta-Naphthoflavone 
                 Ozone 
               
               
                 1-Methyl-3-isobutylxanthine  
                 gatifloxacin 
                 Methimazole 
               
               
                 2-Acetylaminofluorene 
                 peginterferon alfa-2a 
                 Tetradecanoylphorbol 
               
               
                   
                   
                 Acetate 
               
               
                 Etoposide 
                 docetaxel 
                 beta-glycerophosphoric acid 
               
               
                 leflunomide 
                 Indomethacin 
                 Diclofenac 
               
               
                 Formaldehyde 
                 Cyclophosphamide 
                 Methotrexate 
               
               
                 Valproic Acid 
                   
                   
               
            
           
           
               
            
               
                 J1. Molecules that upregulate SLC6A20: 
               
            
           
           
               
               
               
            
               
                 Sulfamerazine 
                 sodium selenate 
                 gefitinib 
               
               
                 dibenzazepine 
                 Hemin 
                 N,N-dimethylarginine 
               
               
                 aluminum sulfate 
                 fingolimod 
                 7-aminocephalosporanic acid 
               
               
                 1-Methyl-4-phenyl-1,2,3,6- 
                 MRK 003 
                 everolimus 
               
               
                 tetrahydropyridine 
                   
                   
               
               
                 acodazole 
                 SB 203580 
                 carbinoxamine 
               
               
                 Curcumin 
                 Pizotyline 
                 Cephalexin 
               
               
                 picrotoxinin 
                 trichlorofluoromethane 
                 Chlorhexidine 
               
               
                 bis(tri-n-butyltin)oxide 
                 Perhexiline 
                 picotamide 
               
               
                 Tetradecanoylphorbol Acetate 
                 Particulate Matter 
                 naphthalan 
               
               
                 thioperamide 
                 Fursultiamin 
                 levocabastine 
               
               
                 erlotinib 
                 isocorydine 
                 ochratoxin A 
               
               
                 Cyclopenthiazide 
                 SEW2871 
                 esculetin 
               
               
                 Atractyloside 
                 Dihydrostreptomycin 
                 lobelanidine 
               
               
                   
                 Sulfate 
                   
               
               
                 acetorphan 
                 Vehicle Emissions 
                 Naltrexone 
               
               
                 Loxapine 
                 medrysone 
                 Pancuronium 
               
               
                 Ultraviolet Rays 
                 cyanoginosin LR 
                 Dichlororibofuranosylbenzimidazole 
               
               
                 N-(2-cyclohexyloxy-4- 
                 Pentetic Acid 
                 iodoform 
               
               
                 nitrophenyl)methanesulfonamide 
                   
                   
               
               
                 Pheniramine 
                 Indapamide 
                 Meptazinol 
               
               
                 Flutamide 
                 Acebutolol 
                 Edrophonium 
               
               
                 Spiramycin 
                 Etiocholanolone 
                 Alprostadil 
               
               
                 boldine 
                 asiaticoside 
                 Loperamide 
               
               
                 Sulfamethazine 
                 gibberellic acid 
                 citiolone 
               
               
                 vanoxerine 
                 Cefotaxime 
                 Bicuculline 
               
               
                 pyrvinium 
                 hesperetin 
                 Isradipine 
               
               
                 Tiapamil Hydrochloride 
                 Suloctidil 
                 Ganciclovir 
               
               
                 Paraquat 
                 Selegiline 
                 Mesalamine 
               
               
                 diphenidol 
                 Clodronic Acid 
                 decitabine 
               
               
                 Dilazep 
                 Bleomycin 
                 Hexetidine 
               
               
                 Meclofenoxate 
                 clemizole 
                 Paclitaxel 
               
               
                 bicalutamide 
                 Gabexate 
                 Enterotoxins 
               
               
                 Heparin 
                 Am iloride 
                 triptolide 
               
               
                 Cytokines 
                 Metribolone 
                 enzastaurin 
               
               
                 Tranylcypromine 
                 Am 580 
                 enterotoxin B, staphylococcal 
               
               
                 flunisolide 
                 Carboplatin 
                 Zinc Oxide 
               
               
                 Methylnitrosourea 
                 trichostatin A 
                 pramoxine 
               
               
                 Sirolimus 
                 Phenelzine 
                 Hydrogen Peroxide 
               
               
                 Reserpine 
                 Genistein 
                 phosphonoacetamide 
               
               
                 Primaquine 
                 Dihydrotestosterone 
                 Flurbiprofen 
               
               
                 Clonidine 
                 glimepiride 
                 Carbimazole 
               
               
                 Fenoprofen 
                 Fluorouracil 
                 Chlorambucil 
               
               
                 Naproxen 
                 Roxithromycin 
                 Valproic Acid 
               
               
                 Chloroquine 
                 Probenecid 
                 geldanamycin 
               
               
                 Ergocalciferols 
                 Cortisone 
                 Phenobarbital 
               
               
                 Acyclovir 
                 Nitrofurantoin 
                 Pyrogens 
               
               
                 Calcium 
                 Neomycin 
                 Ifosfamide 
               
               
                 R 848 
                 X-Rays 
                 imatinib 
               
               
                 gatifloxacin 
                 resveratrol 
                 Cyclosporine 
               
               
                 Quercetin 
                 Nifedipine 
                 Ranitidine 
               
               
                 Azithromycin 
                 Benzo(a)pyrene 
                 Doxorubicin 
               
               
                 Diethylstilbestrol 
                 Tretinoin 
                 Methyl Methanesulfonate 
               
               
                 Lactic Acid 
                 Azacitidine 
                 Methapyrilene 
               
               
                 Acetaminophen 
                 Cisplatin 
                   
               
            
           
           
               
            
               
                 J2. Molecules that downregulate SLC6A20: 
               
            
           
           
               
               
               
            
               
                 Go 6976 
                 Progesterone 
                 Parathion 
               
               
                 testosterone 17 beta- 
                 Apomorphine 
                 Fonofos 
               
               
                 cypionate 
                   
                   
               
               
                 Alpha-Amanitin 
                 Shiga Toxin 
                 Grape Seed 
               
               
                   
                   
                 Proanthocyanidins 
               
               
                 shikonin 
                 Malathion 
                 sulfanilamide 
               
               
                 Fusaric Acid 
                 polidocanol 
                 Teriparatide 
               
               
                 Doxylamine 
                 tibolone 
                 Ethylene Oxide 
               
               
                 mefexamide 
                 infliximab 
                 quintozene 
               
               
                 Arecoline 
                 Dextran Sulfate 
                 caffeic acid 
               
               
                 Gonadotropins 
                 Estradiol 
                 acyline 
               
               
                 gabapentin 
                 Puromycin 
                 chlorcyclizine 
               
               
                 sodium arsenite 
                 3-deazaneplanocin 
                 Hydrochloric Acid 
               
               
                 estradiol 3-benzoate 
                 Isoniazid 
                 Folic Acid 
               
               
                 nilutamide 
                 Eugenol 
                 imiquimod 
               
               
                 Levodopa 
                 Rifampin 
                 Diethylhexyl Phthalate 
               
               
                 Chorionic Gonadotropin 
                 Epitestosterone 
                 Deoxyglucose 
               
               
                 Luteinizing Hormone 
                 Cocaine 
                 Zinc 
               
               
                 rosiglitazone 
                 Anti-Retroviral Agents 
                 bromodichloromethane 
               
               
                 Captopril 
                 Azoxymethane 
                 bisphenol A 
               
               
                 Choline 
                 Methylene Chloride 
                 Tetrachlorodibenzodioxin 
               
               
                 efavirenz 
                 Deferoxamine 
                 Cholecalciferol 
               
               
                 bortezomib 
                 vorinostat 
                 Dexamethasone 
               
               
                 Clomipramine 
                 Lamivudine 
                 Etoposide 
               
               
                 Diclofenac 
                 Fluoxetine 
                 Metformin 
               
            
           
           
               
            
               
                 K1. Molecules that upregulate SLC6A13: 
               
            
           
           
               
               
               
            
               
                 sapphyrin 
                 1-(5- 
                 Furosemide 
               
               
                   
                 Isoquinolinesulfonyl)-2- 
                   
               
               
                   
                 Methylpiperazine 
                   
               
               
                 Diethylhexyl Phthalate 
                 Chitosan 
                 triptolide 
               
               
                 Clofibrate 
                 Ethyl Methanesulfonate 
                 monastrol 
               
               
                 Digitoxin 
                 Isoflurane 
                 Carteolol 
               
               
                 phosphonoacetamide 
                 Zinc Oxide 
                 fosfosal 
               
               
                 topiramate 
                 Mexiletine 
                 Carbarson 
               
               
                 2-nitrofluorene 
                 flunisolide 
                 tiaprofenic acid 
               
               
                 sildenafil 
                 Estradiol 
                 Sulfameter 
               
               
                 Proglumide 
                 Cytokines 
                 butenafine 
               
               
                 deferiprone 
                 hexachloroethane 
                 Ethylene Glycol 
               
               
                 Lidoflazine 
                 sulforafan 
                 cefepime 
               
               
                 carcinine 
                 Amiodarone 
                 tenoxicam 
               
               
                 prednicarbate 
                 Meclofenamic Acid 
                 Acetaminophen 
               
               
                 lead tetraacetate 
                 midecamycin 
                 myricetin 
               
               
                 Clarithromycin 
                 Lithium Chloride 
                 trovafloxacin 
               
               
                 Propranolol 
                 Amprolium 
                 Simvastatin 
               
               
                 shikonin 
                 glycidol 
                 ochratoxin A 
               
               
                 scriptaid 
                 sodium chlorate 
                 Puromycin 
               
               
                   
                   
                 Aminonucleoside 
               
               
                 VX 
                 sulfathiazole 
                 Talampicillin 
               
               
                 Isoflurophate 
                 Diclofenac 
                 Auranofin 
               
               
                 torsemide 
                 bendazolic acid 
                 Hymecromone 
               
               
                 Busulfan 
                 Deoxycholic Acid 
                 sparfloxacin 
               
               
                 phenylhydrazine 
                 Vidarabine 
                 Ibuprofen 
               
               
                 Dichlororibofuranosylbenzimidazole 
                 Lomustine 
                 Clofibric Acid 
               
               
                 Mianserin 
                 troglitazone 
                 picotamide 
               
               
                 Pantothenic Acid 
                 Quercetin 
                 Penicillamine 
               
               
                 Polychlorinated Biphenyls 
                 Niacinamide 
                 sodium nitrate 
               
               
                 ponasterone A 
                 Valproic Acid 
                 Indomethacin 
               
               
                 Fenofibrate 
                 oltipraz 
                 Meclofenoxate 
               
               
                 benoxaprofen 
                 Dexamethasone 
                 erlotinib 
               
               
                 Xylazine 
                 Minoxidil 
                 Finasteride 
               
               
                 Sulfachlorpyridazine 
                 Aspirin 
                 diindolylmethane 
               
               
                 amitraz 
                 Chlorzoxazone 
                 tropisetron 
               
               
                 Doxorubicin 
                 Captopril 
                 Meptazinol 
               
               
                 vinylidene chloride 
                 benphothiamine 
                 Azaguanine 
               
               
                 Perhexiline 
                 compactin 
                 phenethyl 
               
               
                   
                   
                 isothiocyanate 
               
               
                 Diquat 
                 Mitomycin 
                 Neomycin 
               
               
                 zaleplon 
                 trichostatin A 
                 Testosterone 
               
               
                 balsalazide 
                 alitretinoin 
                 hesperetin 
               
               
                 Kinetin 
                 Cycloheximide 
                 rofecoxib 
               
               
                 chloroxylenol 
                 Lindane 
                 Dimethylformamide 
               
               
                 sesam in 
                 Ciprofloxacin 
                 Staurosporine 
               
               
                 Vincristine 
                 Cefixime 
                 fluvastatin 
               
               
                 aplidine 
                 Oxyquinoline 
                 Ticrynafen 
               
               
                 Azacitidine 
                 Spironolactone 
                 venlafaxine 
               
               
                 Sulfadoxine 
                 Tocainide 
                 Pregnenolone 
               
               
                 ibufenac 
                 graveoline 
                 1-hydroxycholecalciferol 
               
               
                 Amlodipine 
                 Carmustine 
                 phenothiazine 
               
               
                 Prednisolone 
                 romidepsin 
                 bromfenac 
               
               
                 Procarbazine 
                 Thiabendazole 
                 CPG-oligonucleotide 
               
               
                 tranilast 
                 sodium selenate 
                 Methyl 
               
               
                   
                   
                 Methanesulfonate 
               
               
                 Aristolochic Acids 
                 terbinafine 
                 carbinoxamine 
               
               
                 Digoxin 
                 Gliclazide 
                 Pivampicillin 
               
               
                 leflunomide 
                 oxcarbazepine 
                 Gentamicins 
               
               
                 Fenbendazole 
                 rosiglitazone 
                 decitabine 
               
               
                 Methylcholanthrene 
                 lead acetate 
                 Megestrol Acetate 
               
               
                 Chlorambucil 
                 Pravastatin 
                 homatropine 
               
               
                 dioxybenzone 
                 Betamethasone 
                 6-methoxy-2- 
               
               
                   
                   
                 naphthylacetic acid 
               
               
                 Promethazine 
                 Ritonavir 
                 modafinil 
               
               
                 dexibuprofen 
                 Lovastatin 
                 Kanamycin 
               
               
                 Naproxen 
                 Nevirapine 
                 hydrastinine 
               
               
                 Etoposide 
                 Thioguanine 
                 Triamterene 
               
               
                 Cyproterone Acetate 
                 Ofloxacin 
                 4-dichlorobenzene 
               
               
                 Deferoxamine 
                 nabumetone 
                 sodium arsenite 
               
               
                 R 848 
                 bisphenol A 
                 sangivamycin 
               
               
                 Epirubicin 
                 Benzocaine 
                 wortmannin 
               
               
                 Netilmicin 
                 Nitrofurantoin 
                 1,2,3-trichloropropane 
               
               
                 Raloxifene 
                 Cisplatin 
                 BCG Vaccine 
               
               
                 Canavanine 
                 lamotrigine 
                 hydroxyachillin 
               
               
                 Antibodies, Monoclonal 
                 Nitrofurazone 
                 famciclovir 
               
               
                 Mercuric Chloride 
                 Triiodothyronine 
                 Droperidol 
               
               
                 irinotecan 
                 Acetazolamide 
                 Maprotiline 
               
               
                 Tacrine 
                 Thiostrepton 
                 Lithium 
               
               
                 cerivastatin 
                 Tretinoin 
                 Dibucaine 
               
               
                 Domperidone 
                 Rifabutin 
                 Benzethonium 
               
               
                 Camptothecin 
                 Azoxymethane 
                 Imipramine 
               
               
                 Disopyramide 
                 Pregnenolone 
                 Losartan 
               
               
                   
                 Carbonitrile 
                   
               
               
                 Ketoprofen 
                 Methotrexate 
                 Baclofen 
               
               
                 SU 5402 
                 Vitamin K 3 
                 Diflunisal 
               
               
                 alpha-Tocopherol 
                 vorinostat 
                 Sulpiride 
               
               
                 Luteolin 
                 Cyclosporine 
                 valsartan 
               
               
                 Genistein 
                 phenacemide 
                 1-Methyl-3- 
               
               
                   
                   
                 isobutylxanthine 
               
               
                 Ascorbic Acid 
                 N,N′-diphenyl-4- 
                 2-(4-morpholinyl)-8- 
               
               
                   
                 phenylenediamine 
                 phenyl-4H-1- 
               
               
                   
                   
                 benzopyran-4-one 
               
               
                 Reserpine 
                 Erythromycin 
                 Pergolide 
               
               
                 Streptomycin 
                 Nitric Oxide 
                 Lorazepam 
               
               
                 Chlorpyrifos 
                 lapatinib 
                 Melphalan 
               
               
                 efavirenz 
                 atorvastatin 
                 bortezomib 
               
               
                 Enalapril 
                 Dactinomycin 
                 Fluorouracil 
               
               
                 Lamivudine 
                 Hydroxyurea 
                 Isoproterenol 
               
            
           
           
               
            
               
                 K2. Molecules that down regulate SLC6A13: 
               
            
           
           
               
               
               
            
               
                 Aroclors 
                 ferric nitrilotriacetate 
                 Ethionine 
               
               
                 Aminosalicylic Acid 
                 Methapyrilene 
                 amineptin 
               
               
                 tianeptine 
                 carvedilol 
                 Labetalol 
               
               
                 Paclitaxel 
                 Itraconazole 
                 Yohimbine 
               
               
                 desloratadine 
                 sulconazole 
                 Sotalol 
               
               
                 Methiocarb 
                 Amantadine 
                 coumarin 
               
               
                 Chloroquine 
                 Colchicine 
                 cyanoginosin LR 
               
               
                 TO-901317 
                 Hexachlorobenzene 
                 Doxepin 
               
               
                 Omeprazole 
                 tenidap 
                 Methylcellulose 
               
               
                 piperidolate 
                 Monocrotaline 
                 Estriol 
               
               
                 beta-Naphthoflavone 
                 Ethinyl Estradiol 
                 Safrole 
               
               
                 norethindrone acetate 
                 Chloroform 
                 lansoprazole 
               
               
                 Bacitracin 
                 Tinidazole 
                 Fluoxetine 
               
               
                 Zidovudine 
                 Ketoconazole 
                 Tacrolim us 
               
               
                 Clomipramine 
                 Isotretinoin 
                 gibberellic acid 
               
               
                 Etodolac 
                 Sulfisoxazole 
                 Granisetron 
               
               
                 lobelanidine 
                 Loratadine 
                 Dicumarol 
               
               
                 Citalopram 
                 Cyproterone 
                 Hypericum extract LI 160 
               
               
                 methylparaben 
                 N-nitrosomorpholine 
                 Nortriptyline 
               
               
                 Clozapine 
                 Trimethadione 
                 Metronidazole 
               
               
                 KCB-1 protein, recombinant 
                 epidermal growth factor (1-45) 
                 Ethisterone 
               
               
                 meloxicam 
                 2-Acetylaminofluorene 
                 sunitinib 
               
               
                 Tetracycline 
                 Fursultiamin 
                 Carbenoxolone 
               
               
                 Desipramine 
                 Carbon Tetrachloride 
                 N-acetylsphingosine 
               
               
                 Miconazole 
                 Naloxone 
                 gefitinib 
               
               
                 Amphetamine 
                 Secobarbital 
                 bromobenzene 
               
               
                 valdecoxib 
                 Bretylium Tosylate 
                 Chlorpromazine 
               
               
                 Atropine 
                 nimesulide 
                 Amitriptyline 
               
               
                 Doxapram 
                 Ifosfamide 
                 Lithium Carbonate 
               
               
                 Acebutolol 
                 Khellin 
                 Cinnarizine 
               
               
                 Thioctic Acid 
                 Diethylstilbestrol 
                 piperacetazine 
               
               
                 mebeverine 
                 pralidoxime 
                 Ethambutol 
               
               
                 Mestranol 
                 Clotrimazole 
                 flubendazole 
               
               
                 Methyltestosterone 
                 Sarin 
                 eticlopride 
               
               
                 aristolochic acid I 
                 Diethylnitrosamine 
                 Fonofos 
               
               
                 Mycotoxins 
                 Fluphenazine 
                 Guanfacine 
               
               
                 oxolamine 
                 Metformin 
                 Stavudine 
               
               
                 Teriparatide 
                 apicidin 
                 Stanozolol 
               
               
                 Mephentermine 
                 pantoprazole 
                 Isoniazid 
               
               
                 Deoxyglucose 
                 naringin 
                 Diazepam 
               
               
                 Rifampin 
                 6-Mercaptopurine 
                 crotamiton 
               
               
                 norflurane 
                 4-octylphenol 
                 Sirolimus 
               
               
                 Sulbactam 
                 Cytarabine 
                 Ramipril 
               
               
                 Bicuculline 
                 Vinblastine 
                 Nifedipine 
               
               
                 Paroxetine 
                 Chlortetracycline 
                 sulfabenzamide 
               
               
                 Allopurinol 
                 Cortisone 
                 1,2-dithiol-3-thione 
               
               
                 HC toxin 
                 rabeprazole 
                 Sertraline 
               
               
                 harman 
                 acetovanillone 
                 Mebendazole 
               
               
                 Melatonin 
                 Danazol 
                 Hexamethonium 
               
               
                 letrozole 
                 Choline 
                 marimastat 
               
               
                 Aflatoxin B1 
                 Cetylpyridinium 
                 pristane 
               
               
                 Chlormezanone 
                 Carbamazepine 
                 2,3-dioxo-6-nitro-7- 
               
               
                   
                   
                 sulfamoylbenzo(f)quinoxaline 
               
               
                 Mifepristone 
                 Tamoxifen 
                 Roxithromycin 
               
               
                 4-nonylphenol 
                 DDT 
                 dexamisole 
               
               
                 Ajmaline 
                 Promazine 
                 Folic Acid 
               
               
                 cineole 
                 pioglitazone 
                 Propylthiouracil 
               
               
                 Phenobarbital 
                 Bezafibrate 
                 testosterone 17 beta- 
               
               
                   
                   
                 cypionate 
               
               
                 Abscisic Acid 
                 olanzapine 
                 4-biphenylamine 
               
               
                 salicylamide 
                 Phalloidine 
                 Azithromycin 
               
               
                 beta-cyclodextrin- 
                 Ethionamide 
                 Clonazepam 
               
               
                 benzaldehyde 
                   
                   
               
               
                 Vancomycin 
                 ferulic acid 
                 Tolazamide 
               
               
                 tetrahydrotriamcinolone 
                 Cytochalasin B 
                 Benzo(a)pyrene 
               
               
                 Cyclophosphamide 
                 Azauridine 
                 amlexanox 
               
               
                 Fluocinolone Acetonide 
                 Haloperidol 
                 temozolomide 
               
               
                 Minocycline 
                 nimetazepam 
                 Norethindrone 
               
               
                 sorafenib 
                 nateglinide 
                 Dihydrotestosterone 
               
               
                 2-dichlorobenzene 
                 Tetrachlorodibenzodioxin 
                 Fluconazole 
               
               
                 Alpha-Amanitin 
                 idebenone 
                 Amoxicillin 
               
               
                 Vitamin E 
                 Gemfibrozil 
                 Bromisovalum 
               
               
                 ascorbate-2-phosphate 
                 Catechin 
                 tosufloxacin 
               
               
                 Ampicillin 
                 Nafenopin 
                 Nitrazepam 
               
               
                 Chlormadinone Acetate 
                 anastrozole 
                 Spectinomycin 
               
               
                 Glipizide 
                 Econazole 
                 Clomiphene 
               
               
                 Sulindac 
                 Azathioprine 
                 quetiapine 
               
               
                 Dinitrofluorobenzene 
                 Dimenhydrinate 
                 Clonidine 
               
               
                 Amrinone 
                 Thioacetamide 
                 Levobunolol 
               
               
                 Cephaloridine 
                 Vanadates 
                 Neostigmine 
               
               
                 quintozene 
                 Enoxacin 
                 bromodichloromethane 
               
               
                 diflorasone diacetate 
                 Altretamine 
                 Phenacetin 
               
               
                 Phenelzine 
                 Amoxapine 
                 Streptozocin 
               
               
                 Procainamide 
                 artemisinine 
                 lomefloxacin 
               
               
                 enterotoxin B, 
                 direct black 3 
                 Oxazepam 
               
               
                 staphylococcal 
                   
                   
               
               
                 Lead 
                 estradiol 3-benzoate 
                 alginic acid 
               
               
                 Levonorgestrel 
                 Phenol 
                 Phenformin 
               
               
                 mono-(2-ethylhexyl)phthalate 
                 Chlorpheniramine 
                 LBH589 
               
               
                 Methylnitrosourea 
                 pirinixic acid 
                 Ethacrynic Acid 
               
               
                 Chloramphenicol 
                 Saquinavir 
                 versipelostatin 
               
               
                 Calcitriol 
                 imatinib 
                 6-bromoindirubin-3′-oxime 
               
               
                 doxofylline 
                 Bupropion 
                 perfluorooctanoic acid 
               
               
                 Diltiazem 
                 Caffeine 
                 Disulfiram 
               
               
                 Zalcitabine 
                 Nicotine 
                 Hydroxyzine 
               
               
                 celecoxib 
                 Theophylline 
                 tenofovir 
               
               
                 Perphenazine 
                 Shiga Toxin 
                 Rolipram 
               
               
                 Ticlopidine 
                   
                   
               
            
           
           
               
            
               
                 L1. Molecules that upregulate SLC6A14: 
               
            
           
           
               
               
               
            
               
                 infliximab 
                 moroxydine 
                 Diethylhexyl Phthalate 
               
               
                 Progesterone 
                 N-methylolacrylamide 
                 quintozene 
               
               
                 Calcium 
                 Trichloroepoxypropane 
                 naphthalenediimide 
               
               
                 bisphenol A 
                 Lithium Carbonate 
                 naphthalan 
               
               
                 8-Bromo Cyclic 
                 Vincamine 
                 Vitamin K 2 
               
               
                 Adenosine 
                   
                   
               
               
                 Monophosphate 
                   
                   
               
               
                 Methylene Chloride 
                 cidofovir 
                 Pyrogens 
               
               
                 Dimethylnitrosamine 
                 pipenzolate 
                 Bismuth 
               
               
                 Practolol 
                 dipropizine 
                 Penicillin G 
               
               
                 Ticlopidine 
                 4-hydroxyestradiol-17 
                 8-(3-Chlorostyryl)-1,3,7- 
               
               
                   
                 beta 
                 trimethylxanthine 
               
               
                 Pivampicillin 
                 Quinidine 
                 Ethinyl Estradiol 
               
               
                 Idoxuridine 
                 Terbutaline 
                 BW B70C 
               
               
                 4,5-dianilinophthalimide 
                 Enterotoxins 
                 Netilmicin 
               
               
                 CD 437 
                 1-Methyl-3-isobutylxanthine 
                 Amrinone 
               
               
                 Cefotetan 
                 4′-N-benzoylstaurosporine 
                 N-Methylscopolamine 
               
               
                 vanadium pentoxide 
                 Pregnenolone 
                 Poly I-C 
               
               
                 Hydrochloric Acid 
                 picrotoxinin 
                 Ethynodiol Diacetate 
               
               
                 fenbufen 
                 Hymecromone 
                 Tetracycline 
               
               
                 Pyocyanine 
                 Spectinomycin 
                 Pentamidine 
               
               
                 Ultraviolet Rays 
                 Dibucaine 
                 Cyclopenthiazide 
               
               
                 Tetradecanoylphorbol 
                 Bleomycin 
                 irinotecan 
               
               
                 Acetate 
                   
                   
               
               
                 mycophenolate mofetil 
                 lobelanidine 
                 Proscillaridin 
               
               
                 letrozole 
                 canadine 
                 Metronidazole 
               
               
                 benfluorex 
                 Clobetasol 
                 daidzein 
               
               
                 Cytochalasin B 
                 Antimycin A 
                 vinclozolin 
               
               
                 Lactic Acid 
                 Estrogens 
                 4-methyl-N-(3-(4-methylimidazol-1- 
               
               
                   
                   
                 yl)-5-(trifluoromethyl)phenyl)-3-((4- 
               
               
                   
                   
                 pyridin-3-ylpyrimidin-2- 
               
               
                   
                   
                 yl)amino)benzamide 
               
               
                 wortmannin 
                 Flecainide 
                 Dexamethasone 
               
               
                 Minoxidil 
                 decitabine 
                 Folic Acid 
               
               
                 Vehicle Emissions 
                 Piperonyl Butoxide 
                 Podophyllotoxin 
               
               
                 Dantrolene 
                 Zalcitabine 
                 Dichlororibofuranosylbenzimidazole 
               
               
                 blebbistatin 
                 Ascorbic Acid 
                 Phosgene 
               
               
                 Bupropion 
                 Finasteride 
                 Insulin 
               
               
                 U 0126 
                 Disopyramide 
                 4-nonylphenol 
               
               
                 docetaxel 
                 Epitestosterone 
                 celecoxib 
               
               
                 Particulate Matter 
                 colforsin 
                 acidocin CH5,  Lactobacillus   
               
               
                   
                   
                 
                   acidophilus 
                 
               
               
                 Tetrachlorodibenzodioxin 
                 pralidoxime 
                 quelamycin 
               
               
                 4-(5-benzo(1,3)dioxol-5- 
                 Methapyrilene 
                 Ribavirin 
               
               
                 yl-4-pyridin-2-yl-1H- 
                   
                   
               
               
                 imidazol-2-yl)benzamide 
                   
                   
               
               
                 Dactinomycin 
                 Carboplatin 
                   
               
            
           
           
               
            
               
                 L2. Molecules that downregulate SLC6A14: 
               
            
           
           
               
               
               
            
               
                 1-amino-2,4- 
                 fulvestrant 
                 trimethobenzamide 
               
               
                 dibromoanthraquinone 
                   
                   
               
               
                 Fluocinonide 
                 gefitinib 
                 tetrafluoroethylene 
               
               
                 4-amino-6-hydrazino-7- 
                 iodoform 
                 Norethynodrel 
               
               
                 beta-D-ribofuranosyl-7H- 
                   
                   
               
               
                 pyrrolo(2,3-d)-pyrimidine-5- 
                   
                   
               
               
                 carboxamide 
                   
                   
               
               
                 Dihydroergotamine 
                 solasodine 
                 Benzo(a)pyrene 
               
               
                 Milrinone 
                 Thyroxine 
                 4-acetylaminofluorene 
               
               
                 Estradiol 
                 Levonorgestrel 
                 Dilazep 
               
               
                 Curcumin 
                 Genistein 
                 tris(2,3- 
               
               
                   
                   
                 dibromopropyl)phosphate 
               
               
                 Thiostrepton 
                 verteporfin 
                 15-deoxy-delta(12, 14)- 
               
               
                   
                   
                 prostaglandin J2 
               
               
                 Corticosterone 
                 withaferin A 
                 Diethylstilbestrol 
               
               
                 Azoxymethane 
                 Reserpine 
                 2-methoxyestradiol 
               
               
                 phthalylsulfathiazole  
                 Oxytocin 
                 Apigenin 
               
               
                 Scopolamine Hydrobromide  
                 medrysone 
                 4-biphenylamine 
               
               
                 meropenem 
                 Carbachol 
                 Niridazole 
               
               
                 Chloroquine 
                 4-hydroxytamoxifen 
                 diindolylmethane 
               
               
                 Diazinon 
                 Ethisterone 
                 Isradipine 
               
               
                 Alcuronium 
                 chlorinated dibenzofurans 
                 Trimipramme 
               
               
                 tribenoside 
                 Oxyphenbutazone 
                 tyrphostin AG 1478 
               
               
                 Luteolin 
                 Furazolidone 
                 Atovaquone 
               
               
                 Halcinonide 
                 salmeterol 
                 ergocryptine 
               
               
                 Bromocriptine 
                 ebselen 
                 Clioquinol 
               
               
                 Sulfisoxazole 
                 Promegestone 
                 Am 580 
               
               
                 polidocanol 
                 chloropyramine 
                 Trimethoprim 
               
               
                 fluticasone 
                 Phenoxybenzamine 
                 rottlerin 
               
               
                 piperlonguminine 
                 lansoprazole 
                 mometasone furoate 
               
               
                 hydrastine 
                 flunisolide 
                 Zimeldine 
               
               
                 Amoxicillin 
                 Equilin 
                 Cotinine 
               
               
                 everolimus 
                 skimmianine 
                 17-(dimethylaminoethylamino)- 
               
               
                   
                   
                 17-demethoxygeldanamycin 
               
               
                 harpagoside 
                 bromperidol 
                 Isosorbide 
               
               
                 prednicarbate 
                 rosiglitazone 
                 Theobromine 
               
               
                 Etidronic Acid 
                 Flavoxate 
                 Clofazimine 
               
               
                 sapphyrin 
                 LBH589 
                 Fludrocortisone 
               
               
                 Gossypol 
                 resveratrol 
                 cephaelin 
               
               
                 Felodipine 
                 Malathion 
                 Imipenem 
               
               
                 1-(5-Isoquinolinesulfonyl)-2- 
                 Natamycin 
                 imatinib 
               
               
                 Methylpiperazine  
                   
                   
               
               
                 epitiostanol 
                 zardaverine 
                 Catechin 
               
               
                 phenethyl isothiocyanate  
                 Atenolol 
                 securinine 
               
               
                 17-(allylamino)-17- 
                 6-thioguanosine 
                 Prenylamine 
               
               
                 demethoxygeldanamycin 
                   
                   
               
               
                 sanguinarine 
                 Propidium 
                 discretamine 
               
               
                 Androsterone 
                 Lindane 
                 ciclopirox 
               
               
                 Methylergonovine 
                 dironyl 
                 Betahistine 
               
               
                 Budesonide 
                 famprofazone 
                 Ethacrynic Acid 
               
               
                 Clonidine 
                 tripterine 
                 Metaraminol 
               
               
                 acacetin 
                 Dextran Sulfate 
                 Quercetin 
               
               
                 nifuroxazide 
                 Astemizole 
                 oltipraz 
               
               
                 Dinitrofluorobenzene 
                 Sulfamerazine 
                 methylbenzethonium 
               
               
                 Vancomycin 
                 triptolide 
                 Vitamin K 3 
               
               
                 Tolbutamide 
                 buparvaquone 
                 Cadmium 
               
               
                 sulconazole 
                 enzastaurin 
                 Bucladesine 
               
               
                 Betaxolol 
                 Griseofulvin 
                 Bepridil 
               
               
                 cinchonine 
                 geldanamycin 
                 Azathioprine 
               
               
                 Vitamin E 
                 Sulfamethoxazole 
                 sulforafan 
               
               
                 Trifluoperazine 
                 Paclitaxel 
                 vanoxerine 
               
               
                 monorden 
                 Diclofenac 
                 Doxorubicin 
               
               
                 Tretinoin 
                 parthenolide 
                 Mefloquine 
               
               
                 Tunicamycin 
                 torsemide 
                 Thapsigargin 
               
               
                 Lithium 
                 Promazine 
                 monastrol 
               
               
                 GW 3965 
                 Selenomethionine 
                 Aflatoxin B1 
               
               
                 Primaquine 
                 Hydrocortisone 
                 Raloxifene 
               
               
                 Mexiletine 
                 dibenzazepine 
                 Dipyrone 
               
               
                 Dipyridamole 
                 Freund&#39;s Adjuvant 
                 Papaverine 
               
               
                 2-(4-morpholinyl)-8-phenyl- 
                 Cyclosporine 
                 Hydrogen Peroxide 
               
               
                 4H-1-benzopyran-4-one 
                   
                   
               
               
                 trichostatin A 
                 Valproic Acid 
                 Triiodothyronine 
               
               
                 1-Methyl-4-phenyl-1,2,3,6- 
                 enterotoxin B, 
                 Puromycin 
               
               
                 tetrahydropyridine 
                 staphylococcal 
                   
               
               
                 Isotretinoin 
                 Pyrazinamide 
                 Cycloheximide 
               
               
                 benzyloxycarbonylleucyl- 
                 Estriol 
                 vorinostat 
               
               
                 leucyl-leucine aldehyde 
                   
                   
               
               
                 erlotinib 
                 Testosterone 
                 Nifedipine 
               
               
                 Carbamazepine 
                 dasatinib 
                 Chlorpromazine 
               
               
                 Amiodarone 
                 Hemin 
                 Ketoconazole 
               
               
                 Fluphenazine 
                 Vincristine 
                 Omeprazole 
               
               
                 Sirolimus 
                 Cyclophosphamide 
                 Simvastatin 
               
               
                 Lovastatin 
                 Tamoxifen 
                 Acetaminophen 
               
               
                 Thioacetamide 
                 Ethanol 
                 Cisplatin 
               
            
           
           
               
            
               
                 M1. Molecules that upregulate SLC6A15: 
               
            
           
           
               
               
               
            
               
                 flavanone 
                 PI103 
                 alginic acid 
               
               
                 Ethylene Dibromide 
                 Oxymetholone 
                 Hydroxyzine 
               
               
                 Azacitidine 
                 Cefixime 
                 Cymarine 
               
               
                 4-octylphenol 
                 Dimethadione 
                 Doxycycline 
               
               
                 Megestrol Acetate 
                 Alprazolam 
                 nimesulide 
               
               
                 Diflunisal 
                 nifenazone 
                 versipelostatin 
               
               
                 Finasteride 
                 Diethylstilbestrol 
                 Miconazole 
               
               
                 Calcium 
                 temsirolimus 
                 Idarubicin 
               
               
                 Ethisterone 
                 Mephenytoin 
                 Valproic Acid 
               
               
                 Chorionic Gonadotropin 
                 edelfosine 
                 Carboplatin 
               
               
                 Diethylhexyl Phthalate 
                 vanadyl sulfate 
                 Bromisovalum 
               
               
                 Hydrochloric Acid 
                 Norethindrone 
                 X-Rays 
               
               
                 Econazole 
                 Chlorambucil 
                 leflunomide 
               
               
                 Simvastatin 
                 Trichloroepoxypropane 
                 Chlorpromazine 
               
               
                 Ascorbic Acid 
                 cefepime 
                 Plicamycin 
               
               
                 2-(1H-indazol-4-yl)-6-(4-  
                 LBH589 
                 Ibuprofen 
               
               
                 methanesulfonylpiperazin- 
                   
                   
               
               
                 1-ylmethyl)-4-morpholin-4- 
                   
                   
               
               
                 ylthieno(3,2-d)pyrimidine 
                   
                   
               
               
                 Caerulein 
                 Ethamsylate 
                 Deoxyglucose 
               
               
                 quintozene 
                 pioglitazone 
                 Pargyline 
               
               
                 flumequine 
                 Clopenthixol 
                 gefitinib 
               
               
                 Lactic Acid 
                 amprenavir 
                 N-methylolacrylamide 
               
               
                 Rifampin 
                 Enterotoxins 
                 clemizole 
               
               
                 Ivermectin 
                 Acetylmuramyl-Alanyl- 
                 Nadolol 
               
               
                   
                 Isoglutamine 
                   
               
               
                 Cytokines 
                 Clotrimazole 
                 oxaliplatin 
               
               
                 picotamide 
                 Carbon Tetrachloride 
                 Secobarbital 
               
               
                 bromfenac 
                 beta-cyclodextrin- 
                 Chloroquine 
               
               
                   
                 benzaldehyde 
                   
               
               
                 Rolitetracycline 
                 Niacinamide 
                 MRK 003 
               
               
                 Cytarabine 
                 Equilin 
                 Glycocholic Acid 
               
               
                 Cyclopenthiazide 
                 suxibuzone 
                 tranilast 
               
               
                 Metform in 
                 Isocarboxazid 
                 Hydrocortisone 
               
               
                 ovalicin 
                 vinclozolin 
                 Ethylene Glycol 
               
               
                 Sulindac 
                 dexamisole 
                 Hexestrol 
               
               
                 Aztreonam 
                 Epirizole 
                 Practolol 
               
               
                 tetrahydrotriamcinolone 
                 furaltadon 
                 Carbamazepine 
               
               
                 Nafronyl 
                 3-hydroxyacetanilide 
                 Butyric Acid 
               
               
                 vorinostat 
                 naftopidil 
                 flunisolide 
               
               
                 Sirolimus 
                 Clofibrate 
                 bromobenzene 
               
               
                 Ultraviolet Rays 
                 Acetylcysteine 
                 Methylene Chloride 
               
               
                 atorvastatin 
                 2-m ethoxyestradiol 
                 Zidovudine 
               
               
                 Cholecalciferol 
                 Guanfacine 
                 gatifloxacin 
               
               
                 bortezomib 
                 Puromycin 
                 repaglinide 
               
               
                 6-Mercaptopurine  
                 phthalylsulfathiazole 
                 Mifepristone 
               
               
                 Spectinomycin 
                 candesartan 
                 olanzapine 
               
               
                 beta-glycerophosphoric acid 
                 Ondansetron 
                 Dimenhydrinate 
               
               
                 Kainic Acid 
                 Acepromazine 
                 N-nitrosomorpholine 
               
               
                 Bezafibrate 
                 Tunicamycin 
                 Carbachol 
               
               
                 Deoxycholic Acid 
                 rimexolone 
                 Tobramycin 
               
               
                 Mesalamine 
                 Acetohexamide 
                 Ethosuximide 
               
               
                 Fluorometholone 
                 Piroxicam 
                 Diazepam 
               
               
                 Cyclosporine 
                 Heparin 
                 Naloxone 
               
               
                 Propafenone 
                 Aphidicolin 
                 Bacitracin 
               
               
                 isoascorbic acid 
                 Glyburide 
                 cyclonite 
               
               
                 Baclofen 
                 Methyl Methanesulfonate 
                 Amoxapine 
               
               
                 Gliclazide 
                 Dicumarol 
                 Hydralazine 
               
               
                 Cromolyn Sodium 
                 Clomipramine 
                 Amphetamine 
               
               
                 naphthalan 
                 vinorelbine 
                 sodium arsenite 
               
               
                 Amikacin 
                 Formaldehyde 
                 oxcarbazepine 
               
               
                 Insulin 
                 Levonorgestrel 
                 Amiloride 
               
               
                 Follicle Stimulating 
                 Nitrendipine 
                 Phenacetin 
               
               
                 Hormone 
                   
                   
               
               
                 Asbestos 
                 scriptaid 
                 Particulate Matter 
               
               
                 cerivastatin 
                 4-methyl-N-(3-(4- 
                 sulconazole 
               
               
                   
                 methylimidazol-1-yl)-5- 
                   
               
               
                   
                 (trifluoromethyl)phenyl)-3-  
                   
               
               
                   
                 ((4-pyridin-3-ylpyrimidin-2- 
                   
               
               
                   
                 yl)amino)benzamide 
                   
               
               
                 quetiapine 
                 celecoxib 
                 Thalidomide 
               
               
                 Trenbolone Acetate, 
                 Alpha-Amanitin 
                 Perhexiline 
               
               
                 (17beta)-isomer 
                   
                   
               
               
                 Sulfisoxazole 
                 2-Acetylaminofluorene 
                 Camptothecin 
               
               
                 Zalcitabine 
                 Ergocalciferols 
                 Methylcholanthrene 
               
               
                 Dantrolene 
                 Nortriptyline 
                 Fenofibrate 
               
               
                 Griseofulvin 
                 Amiodarone 
                 Sparteine 
               
               
                 Iproniazid 
                 fomepizole 
                 Ethinyl Estradiol 
               
               
                 torsemide 
                 Luteinizing 
                 Hormone Citalopram 
               
               
                 Lithium 
                 Indomethacin 
                 Methyldopa 
               
               
                 Hydrochlorothiazide 
                 Clofibric Acid 
                 Lovastatin 
               
               
                 Progesterone 
                 zomepirac 
                 Fluorouracil 
               
               
                 Oxymetazoline 
                 Bupropion 
                 meloxicam 
               
               
                 pralidoxime 
                 Danazol 
                 Calcitriol 
               
               
                 Clozapine 
                 Dactinomycin 
                 Ketoconazole 
               
               
                 Colchicine 
                 Hydroxyurea 
                 Ticlopidine 
               
               
                 Azathioprine 
                 Chlorpropamide 
                 Bithionol 
               
               
                 Tacrolimus 
                 Azithromycin 
                 Tetradecanoylphorbol 
               
               
                   
                   
                 Acetate 
               
               
                 Vitamin K 3 
                 Isoniazid 
                 Gemfibrozil 
               
               
                 Atropine 
                 Methapyrilene 
                 Dimethylformamide 
               
               
                 Terbutaline 
                 Isoproterenol 
                   
               
            
           
           
               
            
               
                 M2. Molecules that downregulate SLC6A15: 
               
            
           
           
               
               
               
            
               
                 tianeptine 
                 Rotenone 
                 polidocanol 
               
               
                 Enalapril 
                 3-deazaneplanocin 
                 Hydrogel 
               
               
                 Ranitidine 
                 geldanamycin 
                 Botulinum Toxins 
               
               
                 Antimycin A 
                 1-ethyl-2-benzimidazolinone 
                 epoxomicin 
               
               
                 Mitomycin 
                 Corticosterone 
                 Estriol 
               
               
                 lactacystin 
                 Tretinoin 
                 U 0126 
               
               
                 Vitamin A 
                 4-(4-fluorophenyl)-2-(4- 
                 Gonadotropins 
               
               
                   
                 hydroxyphenyl)-5-(4- 
                   
               
               
                   
                 pyridyl)imidazole 
                   
               
               
                 Amphotericin B 
                 Thioguanine 
                 Fluoxetine 
               
               
                 fasudil  
                 decitabine 
                 Gentamicins 
               
               
                 trichostatin A 
                 Estradiol 
                 1-amino-2,4- 
               
               
                   
                   
                 dibromoanthraquinone 
               
               
                 temozolomide 
                 Pyrazinamide 
                 Cadmium 
               
               
                 Promegestone 
                 Chlorpyrifos 
                 clopidogrel 
               
               
                 Ouabain 
                 mycophenolate mofetil 
                 Diethylnitrosamine 
               
               
                 Timolol 
                 bisphenol A 
                 Ceftriaxone 
               
               
                 25-hydroxycholesterol 
                 Genistein 
                 Tubocurarine 
               
               
                 alpha-Amino-3-hydroxy-5- 
                 Doxorubicin 
                 Etoposide 
               
               
                 methyl-4- 
                   
                   
               
               
                 isoxazolepropionic Acid 
                   
                   
               
               
                 Ifosfamide 
                 Poly I-C 
                 Sumatriptan 
               
               
                 4-(5-benzo(1,3)dioxol-5-yl- 
                 cyanopindolol 
                 bafilomycin A 
               
               
                 4-pyridin-2-yl-1H-imidazol- 
                   
                   
               
               
                 2-yl)benzamide 
                   
                   
               
               
                 Ketamine 
                 Paclitaxel 
                 Sarin 
               
               
                 Sotalol 
                 Procarbazine 
                 Atrazine 
               
               
                 harman 
                 Procainamide 
                 Dexamethasone 
               
               
                 lacidipine 
                 n-hexanal 
                 SB 203580 
               
               
                 Phenylephrine 
                 Chitosan 
                 Quercetin 
               
               
                 17-(allylamino)-17- 
                 Propranolol 
                 lead tetraacetate 
               
               
                 demethoxygeldanamycin 
                   
                   
               
               
                 2-(4-morpholinyl)-8-phenyl- 
                 Streptomycin 
                 Cisplatin 
               
               
                 4H-1-benzopyran-4-one 
                   
                   
               
               
                 efavirenz 
                 Lidocaine 
                 cidofovir 
               
               
                 Carbimazole 
                 sildenafil 
                 Acrolein 
               
               
                 Acyclovir 
                 enterotoxin B, staphylococcal 
                 Y 27632 
               
               
                 Losartan  
                 Lead 
                 Loratadine 
               
               
                 blebbistatin 
                 Bleomycin 
                 4-hydroxytamoxifen 
               
               
                 Dimethyl Sulfoxide 
                 sulforafan 
                 ciprofibrate 
               
               
                 Vecuronium Bromide 
                 N-Methyl-3,4- 
                 linalool 
               
               
                   
                 methylenedioxyamphetamine 
                   
               
               
                 fulvestrant 
                 Immunotoxins 
                 Lamivudine 
               
               
                 Oxazepam 
                 sodium selenate 
                 1-Methyl-3- 
               
               
                   
                   
                 isobutylxanthine 
               
               
                 famciclovir 
                 Folic Acid 
                 Pyrogens 
               
               
                 Anti-Retroviral Agents 
                 Diphenhydramine 
                 triptolide 
               
               
                 Deferoxamine 
                 Metribolone 
                 sanguinarine 
               
               
                 Triiodothyronine 
                 Monocrotaline 
                 gabapentin 
               
               
                 Phenobarbital 
                 Tranylcypromine 
                 erlotinib 
               
               
                 Captopril 
                 Phenytoin 
                 Ozone 
               
               
                 Daunorubicin 
                 Ethanol 
                 Penicillamine 
               
               
                 docetaxel 
                 Tetrachlorodibenzodioxin 
                 imatinib 
               
               
                 Cyclophosphamide 
                 Benzo(a)pyrene 
                 Thapsigargin 
               
               
                 cobaltous chloride 
                 infliximab 
                 rituximab 
               
               
                 rosiglitazone 
                 Dihydrotestosterone 
                 Methotrexate 
               
               
                 Nicotine 
                 Forskolin 
                 Epirubicin 
               
               
                 Levodopa 
                 Choline 
                   
               
            
           
           
               
            
               
                 N1. Molecules that upregulate SLC6A17: 
               
            
           
           
               
               
               
            
               
                 alpha-Amino-3-hydroxy-5-methyl-4- 
                 Deoxycholic Acid 
                 alpha-Tocopherol 
               
               
                 isoxazolepropionic Acid 
                   
                   
               
               
                 gamma-Tocopherol 
                 2-tert-butylhydroquinone 
                 Enterotoxins 
               
               
                 Dactinomycin 
                 Tretinoin 
                 Polychlorinated 
               
               
                   
                   
                 Biphenyls 
               
               
                 trichostatin A 
                 BCG Vaccine 
                 LBH589 
               
               
                 Dichlororibofuranosylbenzimidazole 
                 Hydrocortisone 
                 8-aminohexylamino cAMP 
               
               
                 cobaltous chloride 
                 Oxazepam 
                 buparvaquone 
               
               
                 Bicuculline 
                 vinclozolin 
                 SEW2871 
               
               
                 Epitestosterone 
                 Lithium Chloride 
                 AICA ribonucleotide 
               
               
                 Cholecalciferol 
                 enzastaurin 
                 Bupropion 
               
               
                 SU 5402 
                 Immunoglobulins, 
                 Diethylhexyl Phthalate 
               
               
                   
                 Intravenous 
                   
               
               
                 pirinixic acid 
                 Plicamycin 
                 Bucladesine 
               
               
                 Insulin 
                 Vincristine 
                 1-Methyl-3- 
               
               
                   
                   
                 isobutylxanthine 
               
               
                 Methylene Chloride 
                 Ethanol 
                 Hydroxyurea 
               
               
                 Oxyquinoline 
                 Cycloheximide 
                 Fluoxetine 
               
               
                 Hydrogen Peroxide 
                 decitabine 
                 Growth Hormone 
               
               
                 Cyclosporine 
                 R 848 
                 Deferoxamine 
               
               
                 vorinostat 
                 Methimazole 
                 Quercetin 
               
               
                 Nifedipine 
                 Cisplatin 
                 Testosterone 
               
               
                 Acetaminophen 
                 Doxorubicin 
                 Hemin 
               
               
                 Phenobarbital 
                   
                   
               
            
           
           
               
            
               
                 N2. Molecules that down regulate SLC6A17: 
               
            
           
           
               
               
               
            
               
                 Tranylcypromine 
                 fasudil 
                 Ouabain 
               
               
                 4-hydroxy-2-nonenal 
                 Phorbol Esters 
                 Forskolin 
               
               
                 Pyrazinamide 
                 Ethambutol 
                 Tetrahydrocannabinol 
               
               
                 Rifampin 
                 imiquimod 
                 Lithium 
               
               
                 Staurosporine 
                 Isoniazid 
                 Zinc 
               
               
                 monastrol 
                 HC toxin 
                 lactacystin 
               
               
                 N-Methylaspartate 
                 Dimethyl Sulfoxide 
                 Pentachlorophenol 
               
               
                 Coumaphos 
                 Clodronic Acid 
                 4-biphenylamine 
               
               
                 SB 203580 
                 Levodopa 
                 1-(5-Isoquinolinesulfonyl)-2- 
               
               
                   
                   
                 Methylpiperazine 
               
               
                 Methamphetamine 
                 Hydroxyzine 
                 blebbistatin 
               
               
                 Bleomycin  
                 quintozene 
                 bis(tri-n-butyltin)oxide 
               
               
                 1,2-dilinolenoyl-3-(4- 
                 Camptothecin 
                 scriptaid 
               
               
                 aminobutyryl)propane- 
                   
                   
               
               
                 1,2,3-triol 
                   
                   
               
               
                 phosphonoacetamide 
                 Cefuroxime 
                 Glycerol 
               
               
                 Y 27632 
                 apicidin 
                 Luteinizing Hormone 
               
               
                 bromodichloromethane 
                 Freund&#39;s Adjuvant 
                 Niacinamide 
               
               
                 naphthalene 
                 Ultraviolet Rays 
                 Immunotoxins 
               
               
                 Mycophenolic Acid 
                 Estradiol 
                 resveratrol 
               
               
                 Phytohemagglutinins 
                 Fluorouracil 
                 troglitazone 
               
               
                 Captopril 
                 Azoxymethane 
                 Ozone 
               
               
                 Estriol 
                 Dexamethasone 
                 Rotenone 
               
               
                 gefitinib 
                 CPG-oligonucleotide 
                 quelamycin 
               
               
                 pioglitazone 
                 bisphenol A 
                 rosiglitazone 
               
               
                 Benzo(a)pyrene 
                 Alpha-Amanitin 
                 Methotrexate 
               
               
                 Tamoxifen 
                 Amiodarone 
                 Cyclophosphamide 
               
               
                 Etoposide 
                 Paclitaxel 
                 Tunicamycin 
               
               
                 bortezomib 
                 erlotinib 
                 X-Rays 
               
               
                 Tetradecanoylphorbol 
                 Diethylstilbestrol 
                 Carbon Tetrachloride 
               
               
                 Acetate 
                   
                   
               
               
                 Progesterone 
                 Valproic Acid 
                   
               
            
           
           
               
            
               
                 O1. Molecules that upregulate SLC6A19: 
               
            
           
           
               
               
               
            
               
                 4-hydroxy-2-nonenal 
                 imatinib 
                 pelargonic acid 
               
               
                 neuropeptide Y (18-36) 
                 Paclitaxel 
                 Fenretinide 
               
               
                 Carboplatin 
                 Testosterone 
                 lysophosphatidic acid 
               
               
                 Tetrachlorodibenzodioxin 
                 Platelet Activating Factor 
                 Inosine Monophosphate 
               
               
                 Nicotine 
                 TO-901317 
                 4′-N-benzoylstaurosporine 
               
               
                 5′-methylthioadenosine 
                 fulvestrant 
                 gefitinib 
               
               
                 dihydroquinghaosu 
                 piperaquine 
                 Oxyquinoline 
               
               
                 Doxorubicin  
                 monastrol 
                 sulforafan 
               
               
                 2-methoxyestradiol 
                 SU 5402 
                 sangivamycin 
               
               
                 Sodium Dodecyl Sulfate 
                 decitabine 
                 Nitric Oxide 
               
               
                 Perhexiline 
                 SC 514 
                 imiquimod 
               
               
                 Immunoglobulin G 
                 dibenzazepine 
                 enzastaurin 
               
               
                 Reserpine 
                 Cisplatin 
                 bicalutamide 
               
               
                 testosterone 17 beta- 
                 Cefuroxime 
                 Dactinomycin 
               
               
                 cypionate 
                   
                   
               
               
                 blebbistatin 
                 Methylnitrosourea 
                 vorinostat 
               
               
                 Azacitidine 
                 Estradiol 
                 efavirenz 
               
               
                 Alpha-Amanitin 
                 Enterotoxins 
                 geldanamycin 
               
               
                 Mannitol 
                 Ethanol 
                 Tolbutamide 
               
               
                 Vitamin E 
                 1-Methyl-3-isobutylxanthine  
                 Metformin 
               
               
                 Hydrogen Peroxide 
                 Theophylline 
                 trichostatin A 
               
               
                 Lamivudine 
                 Amphotericin B 
                 2-Acetylaminofluorene 
               
               
                 BCG Vaccine 
                 beta-glycerophosphoric acid 
                 Dexamethasone 
               
               
                 Phenobarbital 
                 Diethylnitrosamine 
                 Cyclosporine 
               
               
                 Methapyrilene 
                 Indomethacin 
                 Colchicine 
               
               
                 Benzo(a)pyrene 
                 nimesulide 
                 Gentamicins 
               
               
                 Sirolimus 
                 Fluorouracil 
                 Doxycycline 
               
               
                 X-Rays 
                 Tretinoin 
                 Acetaminophen 
               
            
           
           
               
            
               
                 O2. Molecules that downregulate SLC6A19: 
               
            
           
           
               
               
               
            
               
                 Fonofos 
                 beta-cyclodextrin- 
                 Parathion 
               
               
                   
                 benzaldehyde 
                   
               
               
                 cyclonite 
                 motexafin gadolinium 
                 8-aminohexylamino cAMP 
               
               
                 phorbolol myristate acetate 
                 R 848 
                 Beclomethasone 
               
               
                 Concanavalin A 
                 alpha-Amino-3-hydroxy-5- 
                 Folic Acid 
               
               
                   
                 methyl-4-isoxazolepropionic Acid 
                   
               
               
                 Ionomyin 
                 alitretinoin 
                 Choline 
               
               
                 Epitestosterone 
                 Cholecalciferol 
                 Ascorbic Acid 
               
               
                 Tetradecanoylphorbol 
                 shikonin 
                 direct black 3 
               
               
                 Acetate 
                   
                   
               
               
                 Am 580 
                 Anti-Retroviral Agents 
                 Deoxyglucose 
               
               
                 sodium arsenite 
                 Freund′s Adjuvant 
                 Brefeldin A 
               
               
                 Palmitic Acid 
                 aluminum sulfate 
                 Poly I-C 
               
               
                 Bicuculline 
                 infliximab 
                 Chloroquine 
               
               
                 Dinitrofluorobenzene 
                 pioglitazone 
                 Cycloheximide 
               
               
                 Phytohemagglutinins 
                 Kainic Acid 
                 CPG-oligonucleotide 
               
               
                 Tamoxifen 
                 Captopril 
                 bisphenol A 
               
               
                 Insulin 
                 rituximab 
                 Dihydrotestosterone 
               
               
                 Methotrexate 
                 Ribavirin 
                 Carbon Tetrachloride 
               
            
           
           
               
            
               
                 P1. Molecules that upregulate SLC38A2: 
               
            
           
           
               
               
               
            
               
                 2-tert-butyl-9-fluoro-3,6-dihydro-7H- 
                 apratoxin A 
                 1-hydroxycholecalciferol 
               
               
                 benz(h)imidazo(4,5-f)isoquinoline-7-one 
                   
                   
               
               
                 Niacin 
                 2-Acetylaminofluorene 
                 Zalcitabine 
               
               
                 pyrvinium 
                 eseroline 
                 Clomipramine 
               
               
                   
                 N,N′-diphenyl-4- 
                 Tranylcypromine 
               
               
                 Ethionamide 
                 phenylenediamine 
                   
               
               
                 motexafin gadolinium 
                 Dichlorvos 
                 closantel 
               
               
                 Phenacetin 
                 Aspirin 
                 methylparaben 
               
               
                 Sotalol 
                 phenylhydrazine 
                 methyl salicylate 
               
               
                 ferulic acid 
                 salicylamide 
                 Clarithromycin 
               
               
                 Chlorpromazine 
                 Caffeine 
                 compactin 
               
               
                 lactacystin 
                 Niclosamide 
                 Nitrofurantoin 
               
               
                 ibufenac 
                 trovafloxacin 
                 Bromhexine 
               
               
                 temafloxacin 
                 Praziquantel 
                 Rolipram 
               
               
                 Shiga Toxin 
                 Methazolamide 
                 Fenbendazole 
               
               
                 Cinnarizine 
                 Thioridazine 
                 Mianserin 
               
               
                 Ergocalciferols 
                 Carbamazepine 
                 Theophylline 
               
               
                 Baclofen 
                 Monensin 
                 Cholecalciferol 
               
               
                 Foscarnet 
                 chloropyramine 
                 Gentian Violet 
               
               
                 Norepinephrine 
                 vinylidene chloride 
                 coumarin 
               
               
                 ipriflavone 
                 Trimeprazine 
                 Buthionine Sulfoximine 
               
               
                 Ticrynafen 
                 zaleplon 
                 Fluphenazine 
               
               
                 Chloramphenicol 
                 Acetaminophen 
                 butenafine 
               
               
                 Chlorhexidine 
                 Doxepin 
                 Aflatoxin B1 
               
               
                 piclamilast 
                 tranilast 
                 dimethisoquin 
               
               
                 Megestrol 
                 balsalazide 
                 romidepsin 
               
               
                 Yellow Fever Vaccine 
                 Methanol 
                 nateglinide 
               
               
                 Sulindac 
                 Digoxin 
                 Methotrimeprazine 
               
               
                 glimepiride 
                 Nitrazepam 
                 Prednisolone 
               
               
                 Phosgene 
                 bendazolic acid 
                 Methocarbamol 
               
               
                 Bisacodyl 
                 cyanoginosin LR 
                 Dimaprit 
               
               
                 Disulfiram 
                 Glutamic Acid 
                 PI103 
               
               
                 Dimethylformamide 
                 Cephalothin 
                 methylbenzethonium 
               
               
                 hydrazine 
                 Strophanthidin 
                 zileuton 
               
               
                 Mefenamic Acid 
                 alclometasone dipropionate 
                 Methyltestosterone 
               
               
                 profenamine 
                 Vecuronium Bromide 
                 troglitazone 
               
               
                 Halcinonide 
                 GW 3965 
                 Metronidazole 
               
               
                 oxfendazole 
                 wortmannin 
                 Dequalinium 
               
               
                 Lindane 
                 Pemoline 
                 Lasalocid 
               
               
                 ONO 2235 
                 Cymarine 
                 1,3-dichloro-2-propanol 
               
               
                 Stanozolol 
                 Amantadine 
                 Thioacetamide 
               
               
                 amitraz 
                 Morphine 
                 Gossypol 
               
               
                 cloperastine 
                 Chlorambucil 
                 Budesonide 
               
               
                 Verapamil 
                 Safrole 
                 Fluocinolone Acetonide 
               
               
                 Chloroform 
                 Capsaicin 
                 Amiodarone 
               
               
                 Isoniazid 
                 beta-cyclodextrin-benzaldehyde 
                 bromfenac 
               
               
                 Lithocholic Acid 
                 Cyclophosphamide 
                 Pizotyline 
               
               
                 Clofibric Acid 
                 methixene 
                 Colchicine 
               
               
                 Domperidone 
                 Albendazole 
                 Fluocinonide 
               
               
                 U 54494A 
                 lysophosphatidic acid 
                 Zinc Oxide 
               
               
                 benzamil 
                 amlexanox 
                 Bupropion 
               
               
                 Trimipramine 
                 CEP 14083 
                 Digitoxigenin 
               
               
                 homochlorocyclizine 
                 Diquat 
                 Dicyclomine 
               
               
                 Tolazamide 
                 thioperamide 
                 Estradiol 
               
               
                 Methyl Methanesulfonate 
                 Dimethylnitrosamine 
                 Chlormadinone Acetate 
               
               
                 Fludrocortisone 
                 Amphetamine 
                 Inosine Monophosphate 
               
               
                 Proglumide 
                 Altretamine 
                 Methiothepin 
               
               
                 systhane 
                 Aldosterone 
                 Chloroquine 
               
               
                 Niacinamide 
                 Naproxen 
                 Desipramine 
               
               
                 Proadifen 
                 rimexolone 
                 Lidoflazine 
               
               
                 Pyrilamine 
                 cetraxate 
                 cerivastatin 
               
               
                 Ibuprofen 
                 Gentamicins 
                 Deoxycholic Acid 
               
               
                 Pyrazinamide 
                 Minocycline 
                 Azaperone 
               
               
                 Methapyrilene 
                 Tunicamycin 
                 Amlodipine 
               
               
                 CPG-oligonucleotide 
                 Clomiphene 
                 nebivolol 
               
               
                 phenothiazine 
                 Amoxicillin 
                 hydroquinidine 
               
               
                 estradiol 3-benzoate 
                 Propafenone 
                 Albuterol 
               
               
                 amineptin 
                 Folic Acid 
                 Cyclosporine 
               
               
                 Estriol 
                 2-(4-morpholinoanilino)- 
                 Tacrine 
               
               
                   
                 6-cyclohexylaminopurine 
                   
               
               
                 olanzapine 
                 tetrandrine 
                 Epirubicin 
               
               
                 Enalapril 
                 Dexamethasone 
                 Neostigmine 
               
               
                 Histidinol 
                 Trihexyphenidyl 
                 triadimefon 
               
               
                 Pregnenolone 
                 eperisone 
                 irinotecan 
               
               
                 piperacetazine 
                 Indomethacin 
                 Isoflurophate 
               
               
                 Prenylamine 
                 Spironolactone 
                 Diethylnitrosamine 
               
               
                 Fluvoxamine 
                 Sirolimus 
                 3-hydroxyacetanilide 
               
               
                 Mustard Gas 
                 alpha-Amino-3-hydroxy- 
                   
               
               
                   
                 5-methyl-4-isoxazolepropionic Acid 
                 MF59 oil emulsion 
               
               
                 bisphenol A 
                 Rifabutin 
                 Fluspirilene 
               
               
                 meloxicam 
                 anastrozole 
                 Proscillaridin 
               
               
                 Berberine 
                 N-acetylsphingosine 
                 leflunomide 
               
               
                 Roflumilast 
                 Bepridil 
                 Benzo(a)pyrene 
               
               
                 Mesoridazine 
                 Oxprenolol 
                 letrozole 
               
               
                 hydroquinone 
                 halofuginone 
                 flunisolide 
               
               
                 ubiquinol 
                 Aflatoxins 
                 piperlonguminine 
               
               
                 halofantrine 
                 Ethyl Methanesulfonate 
                 lanatoside C 
               
               
                 Ethambutol 
                 Protriptyline 
                 bromobenzene 
               
               
                 calmidazolium 
                 Monocrotaline 
                 Etodolac 
               
               
                 Thiorphan 
                 nimesulide 
                 Triprolidine 
               
               
                 acemetacin 
                 Spiperone 
                 Triiodothyronine 
               
               
                 Prednisone 
                 tenidap 
                 Prochlorperazine 
               
               
                 Melatonin 
                 Methyldopa 
                 cobaltous chloride 
               
               
                 direct black 3 
                 Alprazolam 
                 monobenzone 
               
               
                 KCB-1 protein, recombinant 
                 epidermal growth factor (1-45) 
                 Ciprofloxacin 
               
               
                 2-dichlorobenzene 
                 gefitinib 
                 Triamterene 
               
               
                 Trifluoperazine 
                 Zidovudine 
                 diflorasone diacetate 
               
               
                 Choline 
                 chlorcyclizine 
                 Carmustine 
               
               
                 Hydralazine 
                 Finasteride 
                 Thapsigargin 
               
               
                 valsartan 
                 medrysone 
                 Beclomethasone 
               
               
                 geraniol 
                 Tetradecanoylphorbol Acetate 
                 Itraconazole 
               
               
                 Erythromycin 
                 Imipramine 
                 Fendiline 
               
               
                 Lovastatin 
                 Astern izole 
                 Dihydrotestosterone 
               
               
                 4-acetylaminofluorene 
                 Methylprednisolone 
                 mometasone furoate 
               
               
                 Puromycin 
                 Ceftriaxone 
                 venlafaxine 
               
               
                 Aminonucleoside 
                   
                   
               
               
                 nickel chloride 
                 Chlorprothixene 
                 pantoprazole 
               
               
                 TO-901317 
                 Proguanil 
                 Phenylbutazone 
               
               
                 Tranexamic Acid 
                 Clemastine 
                 pramoxine 
               
               
                 Danazol 
                 R 848 
                 Cisapride 
               
               
                 Diclofenac 
                 parbendazole 
                 oxidized-L-alpha-1-palmitoyl-2- 
               
               
                   
                   
                 arachidonoyl-sn-glycero-3- 
               
               
                   
                   
                 phosphorylcholine 
               
               
                 Pyrogens 
                 Vanadates 
                 lansoprazole 
               
               
                 Azathioprine 
                 Mycophenolic Acid 
                 Ethylene Glycol 
               
               
                 Nefopam 
                 Norethynodrel 
                 clemizole 
               
               
                 tripterine 
                 nisoxetine 
                 Tamoxifen 
               
               
                 Chlormezanone 
                 Nitrofurazone 
                 Mefloquine 
               
               
                 eticlopride 
                 Tetracycline 
                 Omeprazole 
               
               
                 vanoxerine 
                 Thiethylperazine 
                 marimastat 
               
               
                 dibenzazepine 
                 lingzhi 
                 prednicarbate 
               
               
                 Desoxycorticosterone 
                 Oxyquinoline 
                 Cyproheptadine 
               
               
                 tetrahydrotriamcinolone 
                 Hexetidine 
                 4-hydroxy-2-nonenal 
               
               
                 bortezomib 
                 Captopril 
                 Promethazine 
               
               
                 Diazinon 
                 Iproniazid 
                 pimethixene 
               
               
                 Propranolol 
                 Vinblastine 
                 doxofylline 
               
               
                 Brefeldin A 
                 Hydroxyzine 
                 asperflavin 
               
               
                 ursolic acid 
                 Enoxacin 
                 Acetazolamide 
               
               
                 Nocodazole 
                 1-Methyl-4-phenyl- 
                 Saquinavir 
               
               
                   
                 1,2,3,6-tetrahydropyridine 
                   
               
               
                 Ouabain 
                 Metergoline 
                 Sumatriptan 
               
               
                 boldine 
                 Stavudine 
                 N-(2-cyclohexyloxy-4- 
               
               
                   
                   
                 nitrophenyl)methanesulfonamide 
               
               
                 Pravastatin 
                 Nystatin 
                 chelidonine 
               
               
                 Diazepam 
                 N, N-dimethylarginine 
                 Perphenazine 
               
               
                 dasatinib 
                 Pergolide 
                 Podophyllotoxin 
               
               
                 Orphenadrine 
                 Haloperidol 
                 Ketorolac 
               
               
                 Palmitic Acid 
                 Promazine 
                 Dizocilpine Maleate 
               
               
                 Tinidazole 
                 sodium arsenite 
                 Furosemide 
               
               
                 Diphenhydramine 
                 Loxapine 
                 bafilomycin A 
               
               
                 Maprotiline 
                 Propylthiouracil 
                 Isoproterenol 
               
               
                 Clopenthixol 
                 Methamphetamine 
                 Perhexiline 
               
               
                 4-(5-benzo(1,3)dioxol-5-yl- 
                 rabeprazole 
                 Oxymetazoline 
               
               
                 4-pyridin-2-yl-1H-imidazol- 
                   
                   
               
               
                 2-yl)benzamide 
                   
                   
               
               
                 Pimozide 
                 2-methoxyestradiol 
                 Nafenopin 
               
               
                 Thioguanine 
                 2-(4-morpholinyl)-8-phenyl-4H-1- 
                 Penicillamine 
               
               
                   
                 benzopyran-4-one 
                   
               
               
                 6-Mercaptopurine 
                 phenacemide 
                 Labetalol 
               
               
                 Loratadine 
                 Nordihydroguaiaretic 
                 Ethacrynic Acid 
               
               
                   
                 Acid 
                   
               
               
                 Nicotine 
                 Lobeline 
                 Phenoxybenzamine 
               
               
                 Mephentermine 
                 candesartan 
                 fluvastatin 
               
               
                 acadesine 
                 idebenone 
                 6-methoxy-2-naphthylacetic acid 
               
               
                 Chitosan 
                 Fluconazole 
                 Meclizine 
               
               
                 Citalopram 
                 Ifosfamide 
                 Acetylcysteine 
               
               
                 desloratadine 
                 Nevirapine 
                 Nitric Oxide 
               
               
                 fragment C, human serum albumin 
                 Risperidone 
                 resveratrol 
               
               
                 Amiloride 
                 Soman 
                 benzyloxycarbonylleucyl-leucyl- 
               
               
                   
                   
                 leucine aldehyde 
               
               
                 Chlorpyrifos 
                 Puromycin 
                 Quinidine 
               
               
                 HI 6 
                 alpha-Tocopherol 
                 Streptomycin 
               
               
                 2-(1H-indazol-4-yl)-6-(4- 
                 Rifampin 
                 carvedilol 
               
               
                 methanesulfonylpiperazin- 
                   
                   
               
               
                 1-ylmethyl)-4-morpholin-4- 
                   
                   
               
               
                 ylthieno(3,2-d)pyrimidine 
                   
                   
               
               
                 Staurosporine 
                 1-Methyl-3-isobutylxanthine 
                 Moxisylyte 
               
               
                 lamotrigine 
                 Ketoprofen 
                 perfluorooctanoic acid 
               
               
                 MRK 003 
                 Vitamin K 3 
                 Nifedipine 
               
               
                 erlotinib 
                 Aminoglutethimide 
                 Phytohemagglutinins 
               
               
                 Methotrexate 
                 Fluorouracil 
                 Diltiazem 
               
               
                 Ribavirin 
                 Clozapine 
                   
               
            
           
           
               
            
               
                 P2. Molecules that downregulate SLC38A2: 
               
            
           
           
               
               
               
            
               
                 ellipticine 
                 Mitoxantrone 
                 4′-epidaunomycin 
               
               
                 N(1)-methyl-2-lysergic 
                 midecamycin 
                 triptolide 
               
               
                 acid diethylamide 
                   
                   
               
               
                 Echinomycin 
                 Paraoxon 
                 quelamycin 
               
               
                 Busulfan 
                 Dactinomycin 
                 sapphyrin 
               
               
                 Buformin 
                 Deoxyglucose 
                 Chlortetracycline 
               
               
                 Phenformin  
                 Papaverine 
                 Alpha-Amanitin 
               
               
                 Econazole 
                 cephaelin 
                 versipelostatin 
               
               
                 Coumarins 
                 perfosfamide 
                 Aclarubicin 
               
               
                 Polychlorinated Biphenyls  
                 Diamide 
                 Adenosine-5′-(N- 
               
               
                   
                   
                 ethylcarboxamide) 
               
               
                 sesamin 
                 Metformin 
                 Terfenadine 
               
               
                 Antazoline 
                 Cyproterone Acetate 
                 CpG ODN 2216 
               
               
                 iodoform 
                 Butyric Acid 
                 Deferoxamine 
               
               
                 Nisoldipine 
                 Cortisone 
                 Cyclandelate 
               
               
                 oltipraz 
                 Emetine 
                 tenofovir 
               
               
                 flavopiridol 
                 insulin-like growth factor I (57-70) 
                 8-aminohexylamino cAMP 
               
               
                 Ketoconazole 
                 Hycanthone 
                 verteporfin 
               
               
                 neuropeptide Y (18-36) 
                 amprenavir 
                 1-(2-cyano-3,12-dioxooleana- 
               
               
                   
                   
                 1,9-dien-28-oyl) imidazole 
               
               
                 Guanethidine 
                 apicidin 
                 Ultraviolet Rays 
               
               
                 Methylcholanthrene 
                 Dinoprostone 
                 Sulpiride 
               
               
                 Atovaquone 
                 Ceftazidime 
                 aluminum sulfate 
               
               
                 Zinc Sulfate 
                 dihydroquinghaosu 
                 piperaquine 
               
               
                 beta-Naphthoflavone 
                 Methylnitronitrosoguanidine 
                 Bezafibrate 
               
               
                 Ganciclovir 
                 Fenofibrate 
                 Testosterone 
               
               
                 tropisetron 
                 pirinixic acid 
                 Paclitaxel 
               
               
                 trichostatin A 
                 Triacetin 
                 Secobarbital 
               
               
                 vanadium pentoxide 
                 Doxorubicin 
                 Cantharidin 
               
               
                 Apigenin 
                 Mifepristone 
                 rosiglitazone 
               
               
                 Phenobarbital 
                 anisindione 
                 hydrastine 
               
               
                 gatifloxacin 
                 isoconazole 
                 Lorazepam 
               
               
                 Amoxapine 
                 acidocin CHS, 
                 Hemin 
               
               
                   
                 
                   Lactobacillus acidophilus 
                 
                   
               
               
                 Tretinoin 
                 Carotenoids 
                 Grape Seed Proanthocyanidins 
               
               
                 fasudil 
                 Dimenhydrinate 
                 fipexide 
               
               
                 Immunoglobulin M 
                 grepafloxacin 
                 Oxazepam 
               
               
                 Mebendazole 
                 Trimethadione 
                 blebbistatin 
               
               
                 daboiatoxin 
                 X-Rays 
                 3-nitropropionic acid 
               
               
                 N-Methyl-3,4- 
                 edelfosine 
                 Metribolone 
               
               
                 methylenedioxyamphetamine 
                   
                   
               
               
                 Piperonyl Butoxide 
                 trilinolein 
                 Flurbiprofen 
               
               
                 Cycloheximide 
                 cineole 
                 Y 27632 
               
               
                 Camptothecin 
                 Luteolin 
                 gabapentin 
               
               
                 Pentobarbital 
                 Rotenone 
                 Lidocaine 
               
               
                 Hydrogen Peroxide 
                 Natriuretic Peptide, C-Type 
                 Azithromycin 
               
               
                 Insulin 
                 Nadolol 
                 Ipratropium 
               
               
                   
                   
                 7,8-Dihydro-7,8- 
               
               
                 rofecoxib 
                 pioglitazone 
                 dihydroxybenzo(a)pyrene 9,10- 
               
               
                   
                   
                 oxide 
               
               
                 senecionine 
                 Paroxetine 
                 Ethionine 
               
               
                 Clonazepam 
                 Ethisterone 
                 Poly I-C 
               
               
                 Miconazole 
                 shikonin 
                 Dehydrocholic Acid 
               
               
                 Flunarizine 
                 Tacrolimus 
                 imatinib 
               
               
                 Valproic Acid 
                 naphthalene 
                 Benzalkonium Compounds 
               
               
                 Azacitidine 
                 valdecoxib 
                 atorvastatin 
               
               
                 Clofibrate 
                 bis(tri-n-butyltin)oxide 
                 Genistein 
               
               
                 calycanthine 
                 ethaverine 
                 lacidipine 
               
               
                 alginic acid 
                 Doxapram 
                 4-nonylphenol 
               
               
                 decitabine 
                 Platelet Activating Factor 
                 Timolol 
               
               
                 Chlordiazepoxide 
                 Glyburide 
                 Ranitidine 
               
               
                 vorinostat 
                 2,2′-(hydroxynitrosohydrazono) 
                 Dichlororibofuranosylbenzimidazole 
               
               
                   
                 bis-ethanamine 
                   
               
               
                 4-(4-fluorophenyl)-2-(4- 
                 Clotrimazole 
                 Dobutamine 
               
               
                 hydroxyphenyl)-5-(4- 
                   
                   
               
               
                 pyridyl)imidazole 
                   
                   
               
               
                 Benserazide 
                 4-methyl-N-(3-(4- 
                 Amitriptyline 
               
               
                   
                 methylimidazol-1-yl)-5- 
                   
               
               
                   
                 (trifluoromethyl)phenyl)-3-  
                   
               
               
                   
                 ((4-pyridin-3-ylpyrimidin-2- 
                   
               
               
                   
                 yl)amino)benzamide 
                   
               
               
                 Dimethyl Sulfoxide 
                 Nitroarginine 
                 Malathion 
               
               
                 Metaproterenol 
                 Dacarbazine 
                 Sarin 
               
               
                 Acepromazine 
                 acacetin 
                 Tiapamil Hydrochloride 
               
               
                 discretamine 
                 Concanavalin A 
                 Droperidol 
               
               
                 3-deazaneplanocin 
                 Benperidol 
                 Quinacrine 
               
               
                 Digitoxin 
                 Neomycin 
                 LBH589 
               
               
                 procyanidin 
                 Zimeldine 
                 8-Bromo Cyclic Adenosine 
               
               
                   
                   
                 Monophosphate 
               
               
                 Quercetin 
                 Atropine 
                 U 0126 
               
               
                 dexchlorpheniramine 
                 2,2′-Dipyridyl 
                 Simvastatin 
               
               
                 Plicamycin 
                 Ticlopidine 
                 HC toxin 
               
               
                 sildenafil 
                 1-(5-lsoquinolinesulfonyl)- Famotidine 
                   
               
               
                   
                 2-Methylpiperazine 
                   
               
               
                 ochratoxin A 
                 Vitamin E 
                 Calcitriol 
               
               
                 Phenylephrine 
                 oxybutynin 
                 Mitomycin 
               
               
                 Lomustine 
                 Terazosin 
                 Ethylnitrosourea 
               
               
                 Azauridine 
                 Cytarabine 
                 salmeterol 
               
               
                 efavirenz 
                 scriptaid 
                 Clonidine 
               
               
                 Gemfibrozil 
                 Ascorbic Acid 
                 SU 5402 
               
               
                 17-(allylamino)-17- 
                 SB 203580 
                 Vincristine 
               
               
                 demethoxygeldanamycin 
                   
                   
               
               
                 Clindamycin 
                 Pregnenolone Carbonitrile 
                 Anisomycin 
               
               
                 Losartan 
                 Lamivudine 
                 Ionomyin 
               
               
                 Ramipril 
                 Ofloxacin 
                 Kainic Acid 
               
               
                 NG-Nitroarginine Methyl 
                 Atenolol 
                 gemcitabine 
               
               
                 Ester 
                   
                   
               
               
                 Hydroxyurea 
                 geldanamycin 
                 Terbutaline 
               
               
                 Levodopa 
                 sorafenib 
                 Probucol 
               
               
                 Melphalan 
                 Tocainide 
                   
               
            
           
           
               
            
               
                 Q1. Molecules that upregulate SLC38A4: 
               
            
           
           
               
               
               
            
               
                 2-methoxyestradiol 
                 4-acetylaminofluorene 
                 Captopril 
               
               
                 N-(2-cyclohexyloxy-4- 
                 Hydrocortisone 
                 Sulfaguanidine 
               
               
                 nitrophenyl)methanesulfonamide 
                   
                   
               
               
                 ascorbate-2-phosphate 
                 Isoniazid 
                 6-bromoindirubin-3′-oxime 
               
               
                 Ascorbic Acid 
                 Rifampin 
                 Ethylene Glycol 
               
               
                 Trichloroepoxypropane 
                 SEW2871 
                 sparfloxacin 
               
               
                 Mitomycin 
                 troglitazone 
                 N-Methylaspartate 
               
               
                 Penicillamine 
                 Clarithromycin 
                 8-aminohexylamino cAMP 
               
               
                 vinclozolin 
                 Dihydrotestosterone 
                 Ozone 
               
               
                 Nitrendipine 
                 lapatinib 
                 Sulfisoxazole 
               
               
                 Ergocalciferols 
                 Zalcitabine 
                 Sirolimus 
               
               
                 Dexamethasone 
                 Calcium 
                 Cetylpyridinium 
               
               
                 Mannitol 
                 Dextran Sulfate 
                 Aflatoxin B1 
               
               
                 Ibuprofen 
                 Benzethonium 
                 Theophylline 
               
               
                 4-nonylphenol 
                 aluminum sulfate 
                 ibufenac 
               
               
                 benoxaprofen 
                 Rifabutin 
                 Ciprofloxacin 
               
               
                 meloxicam 
                 Nimodipine 
                 temsirolimus 
               
               
                 methyl salicylate 
                 Azoxymethane 
                 cidofovir 
               
               
                 cryptoxanthin 
                 U 0126 
                 hydrazine 
               
               
                 lead tetraacetate 
                 torsemide 
                 Gentian Violet 
               
               
                 Lomustine 
                 Tryptophan 
                 Valproic Acid 
               
               
                 boldine 
                 trovafloxacin 
                 Probenecid 
               
               
                 Aspirin 
                 flavopiridol 
                 Dimethylnitrosamine 
               
               
                 Doxorubicin 
                 4′-N-benzoylstaurosporine 
                 Procarbazine 
               
               
                 amprenavir 
                 pristane 
                 tosufloxacin 
               
               
                 butenafine 
                 5-fluorouridine 
                 Fluocinolone Acetonide 
               
               
                 arsenic acid 
                 Busulfan 
                 Amphotericin B 
               
               
                 rofecoxib 
                 Hydralazine 
                 phenethyl isothiocyanate 
               
               
                 Atenolol 
                 2-tert-butylhydroquinone 
                 Diethylhexyl Phthalate 
               
               
                 Ethylestrenol 
                 Niacin 
                 Choline 
               
               
                 cilostazol 
                 vinorelbine 
                 Epirubicin 
               
               
                 chloroxylenol 
                 Thioguanine 
                 Chlorambucil 
               
               
                 Chorionic Gonadotropin 
                 ferric nitrilotriacetate 
                 Physostigmine 
               
               
                 Diethylnitrosamine 
                 Indomethacin 
                 Bithionol 
               
               
                 Camptothecin 
                 Caffeine 
                 Nafenopin 
               
               
                 Tiapamil Hydrochloride 
                 Sparteine 
                 Citalopram 
               
               
                 Forskolin 
                 diphenidol 
                 Gentamicins 
               
               
                 pramoxine 
                 Oxyquinoline 
                 Roxithromycin 
               
               
                 Didanosine 
                 Fenofibrate 
                 Betamethasone 
               
               
                 Octopamine 
                 valsartan 
                 Phenacetin 
               
               
                 1-Methyl-3-isobutylxanthine 
                 LPS 9 
                 gefitinib 
               
               
                 diloxanide furoate 
                 estradiol 3-benzoate 
                 Daunorubicin 
               
               
                 sildenafil 
                 Itraconazole 
                 Acetazolamide 
               
               
                 arsenic trioxide 
                 Nortriptyline 
                 Digitoxin 
               
               
                 efavirenz 
                 Clofibrate 
                 3,3′,4′,5-tetrachlorosalicylanilide 
               
               
                 Chlorpromazine 
                 Felodipine 
                 ebastine 
               
               
                 Gonadotropins 
                 Mexiletine 
                 ifenprodil 
               
               
                 Phosgene 
                 Carbimazole 
                 Zidovudine 
               
               
                 Sulfadiazine 
                 Monocrotaline 
                 Diethylstilbestrol 
               
               
                 Etomidate 
                 coumarin 
                 Clomiphene 
               
               
                 Methylcholanthrene 
                 Ouabain 
                 Bezafibrate 
               
               
                 harmol 
                 Dexfenfluramine 
                 Rolipram 
               
               
                 sorafenib 
                 Tolazamide 
                 Meclofenoxate 
               
               
                 Heparin 
                 Promazine 
                 lomefloxacin 
               
               
                 Acyclovir 
                 Amoxicillin 
                 wortmannin 
               
               
                 4-octylphenol 
                 Dimethylformamide 
                 Chloramphenicol 
               
               
                 Mercuric Chloride 
                 Methyldopa 
                 Lamivudine 
               
               
                 fluvastatin 
                 Vitamin K 3 
                 Levonorgestrel 
               
               
                 Ketoconazole 
                 zileuton 
                 glimepiride 
               
               
                 phenothiazine 
                 Vincristine 
                 methyleugenol 
               
               
                 Thalidomide 
                 Fluoxetine 
                 Simvastatin 
               
               
                 zomepirac 
                 Cefuroxime 
                 flubendazole 
               
               
                 N-nitrosomorpholine 
                 Progesterone 
                 Melatonin 
               
               
                 Altretamine 
                 dihydroquinghaosu 
                 piperaquine 
               
               
                 Phenytoin 
                 1,2,3-trichloropropane 
                 Lithocholic Acid 
               
               
                 Levodopa 
                 Mefenamic Acid 
                 nabumetone 
               
               
                 tranilast 
                 idebenone 
                 Etoposide 
               
               
                 Aclarubicin 
                 Neomycin 
                 Methotrexate 
               
               
                 1-(5-lsoquinolinesulfonyl)-2- 
                 Chlormezanone 
                 buflomedil 
               
               
                 Methylpiperazine 
                   
                   
               
               
                 Moxisylyte 
                 artemether 
                 Cocaine 
               
               
                 Bupropion 
                 SU 5402 
                 monastrol 
               
               
                 Sotalol 
                 Pyrazinamide 
                 Methyl Methanesulfonate 
               
               
                 Dicyclomine 
                 Clomipramine 
                 Trimethadione 
               
               
                 Doxycycline 
                 acidocin CH5, 
                 Dichlorvos 
               
               
                   
                 
                   Lactobacillus acidophilus 
                 
                   
               
               
                 acemetacin 
                 Nystatin 
                 dexibuprofen 
               
               
                 Dinitrofluorobenzene 
                 Nevirapine 
                 Stanozolol 
               
               
                 2-Acetylaminofluorene 
                 Ethambutol 
                 Dactinomycin 
               
               
                 Naproxen 
                 Terbutaline 
                 Naloxone 
               
               
                 Fluconazole 
                 Fluorouracil 
                 Amoxapine 
               
               
                 Ultraviolet Rays 
                 Sulfadoxine 
                 Tocainide 
               
               
                 Lactic Acid 
                 6-Mercaptopurine 
                 Stavudine 
               
               
                 Ribavirin 
                 erlotinib 
                 Deoxyglucose 
               
               
                 Spironolactone 
                 R 848 
                 Norethindrone 
               
               
                 olanzapine 
                 Atropine 
                   
               
            
           
           
               
            
               
                 Q2. Molecules that downregulate SLC38A4: 
               
            
           
           
               
               
               
            
               
                 bicalutamide 
                 apicidin 
                 Tolbutamide 
               
               
                 1-amino-2,4- 
                 scriptaid 
                 17-(allylamino)-17- 
               
               
                 dibromoanthraquinone 
                   
                 demethoxygeldanamycin 
               
               
                 Go 6976 
                 LBH589 
                 cobaltous chloride 
               
               
                 vorinostat 
                 Chitosan 
                 Cycloheximide 
               
               
                 Clonidine 
                 Tetanus Toxin 
                 HC toxin 
               
               
                 Cholera Toxin 
                 DDT 
                 2,4-diaminotoluene 
               
               
                 Diazinon 
                 Colchicine 
                 8-Bromo Cyclic Adenosine 
               
               
                   
                   
                 Monophosphate 
               
               
                 infliximab 
                 senecionine 
                 triadimefon 
               
               
                 Risperidone 
                 Hexachlorobenzene 
                 Okadaic Acid 
               
               
                 Sulindac 
                 Omeprazole 
                 Tubocurarine 
               
               
                 Lindane 
                 GW 501516 
                 Simazine 
               
               
                 trichostatin A 
                 Ethylnitrosourea 
                 Cyclosporine 
               
               
                 Coumaphos 
                 Thapsigargin 
                 Danazol 
               
               
                 Tretinoin 
                 pioglitazone 
                 trilinolein 
               
               
                 quintozene 
                 Insulin 
                 cetraxate 
               
               
                 rabeprazole 
                 25-hydroxycholesterol 
                 4′-epidaunomycin 
               
               
                 Sulpiride 
                 Cyclophosphamide 
                 Carmustine 
               
               
                 Propylthiouracil 
                 Nisoldipine 
                 Glycerol 
               
               
                 Noscapine 
                 Lead 
                 Tetradecanoylphorbol 
               
               
                   
                   
                 Acetate 
               
               
                 Cardiotoxins 
                 ovalicin 
                 Medroxyprogesterone 
               
               
                   
                   
                 Acetate 
               
               
                 testosterone 17 beta- 
                 Norepinephrine 
                 Tinidazole 
               
               
                 cypionate 
                   
                   
               
               
                 Azathioprine 
                 hexachlorobutadiene 
                 mono-(2-ethylhexyl)phthalate 
               
               
                 Plicamycin 
                 Disopyramide 
                 Ranitidine 
               
               
                 Labetalol 
                 Perhexiline 
                 ranolazine 
               
               
                 Eugenol 
                 Alpha-Amanitin 
                 Benzbromarone 
               
               
                 famciclovir 
                 beta-Naphthoflavone 
                 Bromocriptine 
               
               
                 Benzo(a)pyrene 
                 cathelicidin antimicrobial peptide 
                 rosiglitazone 
               
               
                 Vecuronium Bromide 
                 Hexachlorophene 
                 Papaverine 
               
               
                 trichlorofluoromethane 
                 (melle-4)cyclosporin 
                 Cisplatin 
               
               
                 clopidogrel 
                 ipriflavone 
                 bendazolic acid 
               
               
                 Beclomethasone 
                 doxofylline 
                 Diclofenac 
               
               
                 Erythromycin 
                 Flutamide 
                 Nifedipine 
               
               
                 cortisone acetate 
                 Phenobarbital 
                 atorvastatin 
               
               
                 Bleomycin 
                 Tunicamycin 
                 geraniol 
               
               
                 Pyrogens 
                 Promethazine 
                 Etidronic Acid 
               
               
                 Tacrine 
                 crotamiton 
                 Caerulein 
               
               
                 Dipyrone 
                 celecoxib 
                 Primidone 
               
               
                 vanadium pentoxide 
                 sodium selenate 
                 sodium arsenite 
               
               
                 Cyproterone Acetate 
                 Ethionine 
                 Terazosin 
               
               
                 Bromhexine 
                 Acetaminophen 
                 Sulbactam 
               
               
                 Miconazole 
                 Malathion 
                 Ticlopidine 
               
               
                 Phenol 
                 Tetrachlorodibenzodioxin 
                 Cadmium 
               
               
                 nitrosobenzylmethylamine 
                 Carbamazepine 
                 Estradiol 
               
               
                 terbinafine 
                 Paclitaxel 
                 Haloperidol 
               
               
                 Aminoglutethimide 
                 Mestranol 
                 Vinblastine 
               
               
                 Methyltestosterone 
                 Palmitic Acid 
                 Carbon Tetrachloride 
               
               
                 Ketorolac 
                 Fenbendazole 
                 Aminosalicylic Acid 
               
               
                 ciprofibrate 
                 Lovastatin 
                 Chlormadinone Acetate 
               
               
                 Cholecalciferol 
                 Tetracaine 
                 genipin 
               
               
                 lead acetate 
                 sulforafan 
                 Nitrofurantoin 
               
               
                 Dantrolene 
                 ferulic acid 
                 Methapyrilene 
               
               
                 Tamoxifen 
                 sulconazole 
                 Clotrimazole 
               
               
                 quetiapine 
                 Isoproterenol 
                 Idarubicin 
               
               
                 Hydroxyzine 
                 Ethinyl Estradiol 
                 Dimenhydrinate 
               
               
                 Azacitidine 
                 Nizatidine 
                 Clonazepam 
               
               
                 Procaine 
                 bromfenac 
                 Pyocyanine 
               
               
                 artemisinine 
                 anastrozole 
                 nimesulide 
               
               
                 Isotretinoin 
                 Tetracycline 
                 Particulate Matter 
               
               
                 decitabine 
                 heliotrine 
                 Furosemide 
               
               
                 Cyproheptadine 
                 MF59 oil emulsion 
                 Bacitracin 
               
               
                 Finasteride 
                 Vitamin E 
                 Salicylic Acid 
               
               
                 Ethanol 
                 Fluphenazine 
                 Acrolein 
               
               
                 Loratadine 
                 Netilmicin 
                 AICA ribonucleotide 
               
               
                 acadesine 
                 lansoprazole 
                 Hydrogen Peroxide 
               
               
                 Gemfibrozil 
                 Cytarabine 
                 Melphalan 
               
               
                 Mitoxantrone 
                 Streptomycin 
                 compactin 
               
               
                 Diazepam 
                 Y 27632 
                 pantoprazole 
               
               
                 Quercetin 
                 Lithium 
                 Chlorzoxazone 
               
               
                 Mifepristone 
                 carvedilol 
                 Deoxycholic Acid 
               
               
                 SB 203580 
                 1,2-dilinolenoyl-3-(4- 
                 bromobenzene 
               
               
                   
                 aminobutyryl)propane-1,2,3-triol 
                   
               
               
                 Acarbose 
                 fulvestrant 
                 Doxapram 
               
               
                 Metform in 
                 Piperonyl Butoxide 
                 leflunomide 
               
               
                 Sulfadimethoxine 
                 Poly I-C 
                 irinotecan 
               
               
                 3-hydroxyacetanilide 
                 acyline 
                 bisphenol A 
               
               
                 Ticrynafen 
                 Dobutamine 
                 Kainic Acid 
               
               
                 2-(4-morpholinyl)-8-phenyl- 
                 Nitrofurazone 
                 Imipramine 
               
               
                 4H-1-benzopyran-4-one 
                   
                   
               
               
                 Minoxidil 
                 norethindrone acetate 
                 Calcitriol 
               
               
                 Tranylcypromine 
                 Chloroform 
                 NG-Nitroarginine Methyl 
               
               
                   
                   
                 Ester 
               
               
                 Lorazepam 
                 Methimazole 
                 Amiodarone 
               
               
                 Chloroquine 
                 Diltiazem 
                 Doxepin 
               
               
                 Sertraline 
                 Amlodipine 
                 Dinoprostone 
               
               
                 Estriol 
                 Ifosfamide 
                 Amantadine 
               
               
                 benzyloxycarbonylleucyl- 
                 2-dichlorobenzene 
                 Genistein 
               
               
                 leucyl-leucine aldehyde 
                   
                   
               
               
                 Carboplatin 
                 pralidoxime 
                 imatinib 
               
               
                 Thioacetamide 
                 Enalapril 
                 Amitriptyline 
               
            
           
           
               
            
               
                 R1. Molecules that upregulate SLC6A7: 
               
            
           
           
               
               
               
            
               
                 Canavanine 
                 Lithium 
                 sodium arsenite 
               
               
                 Theobromine 
                 amprenavir 
                 aceclofenac 
               
               
                 Digitoxin 
                 Nomifensine 
                 diindolylmethane 
               
               
                 Ribostamycin 
                 telenzepine 
                 nabumetone 
               
               
                 Nitrendipine 
                 N-Methyl-3,4- 
                 Hydroxyzine 
               
               
                   
                 methylenedioxyamphetamine 
                   
               
               
                 valsartan 
                 Dimethylformamide 
                 tetrahydrotriamcinolone 
               
               
                 Sulindac 
                 Glycopyrrolate 
                 Clopamide 
               
               
                 Capsaicin 
                 Trichloroacetic Acid 
                 Secobarbital 
               
               
                 Pentobarbital 
                 Nadolol 
                 Aminophylline 
               
               
                 Mitomycin 
                 Aminopyrine 
                 sildenafil 
               
               
                 triptolide 
                 Ketoprofen 
                 trovafloxacin 
               
               
                 4-octylphenol 
                 alverine 
                 Simvastatin 
               
               
                 Diflunisal 
                 Cefmetazole 
                 Ouabain 
               
               
                 Chlorambucil 
                 Hesperidin 
                 Bisacodyl 
               
               
                 phenethyl isothiocyanate 
                 cephalonium 
                 lead acetate 
               
               
                 Clofibrate 
                 Salicylates 
                 moxonidine 
               
               
                 Ticrynafen 
                 Ibuprofen 
                 Dyphylline 
               
               
                 tranilast 
                 Erythromycin Ethylsuccinate 
                 Bithionol 
               
               
                 Progesterone 
                 Digoxin 
                 Sparteine 
               
               
                 buflomedil 
                 Methacycline 
                 esculetin 
               
               
                   
                   
                 4-(N-methyl-N- 
               
               
                 olanzapine 
                 Amantadine 
                 nitrosamino)-1-(3-pyridyl)- 
               
               
                   
                   
                 1-butanone 
               
               
                 Lovastatin 
                 Clarithromycin 
                 carcinine 
               
               
                 oxybutynin 
                 benazepril 
                 Mexiletine 
               
               
                 benoxaprofen 
                 Probucol 
                 Azathioprine 
               
               
                 Gliclazide 
                 Foscarnet 
                 Rifabutin 
               
               
                 Metoprolol 
                 Methyldopa 
                 Finasteride 
               
               
                 Norethindrone 
                 amylocaine 
                 Hydrocortisone 
               
               
                 Hydrochlorothiazide 
                 Econazole 
                 Megestrol Acetate 
               
               
                 Diethylstilbestrol 
                 leflunomide 
                 Sulfadoxine 
               
               
                 Ethamsylate 
                 nimesulide 
                 bromperidol 
               
               
                 Clomiphene 
                 Podophyllotoxin 
                 Chlordiazepoxide 
               
               
                 Citric Acid 
                 Mifepristone 
                 Didanosine 
               
               
                 Canrenoate Potassium 
                 Chlorpromazine 
                 Clonidine 
               
               
                 4-methyl-N-(3-(4-methylimidazol-1-yl)-5- 
                 Flurbiprofen 
                 Stavudine 
               
               
                 (trifluoromethyl)phenyl)-3-((4-pyridin-3- 
                   
                   
               
               
                 ylpyrimidin-2-yl)amino)benzamide 
                   
                   
               
               
                 gabapentin 
                 temafloxacin 
                 Ethisterone 
               
               
                 tenidap 
                 compactin 
                 Procainamide 
               
               
                 Chloroquine 
                 Ranitidine 
                 Aconitine 
               
               
                 Fluconazole 
                 famciclovir 
                 Sulfameter 
               
               
                 ibufenac 
                 Amlodipine 
                 Tetracaine 
               
               
                 diphenidol 
                 vinylidene chloride 
                 Ethanol 
               
               
                 Valproic Acid 
                 flunisolide 
                 clinafloxacin 
               
               
                 Theophylline 
                 Pantothenic Acid 
                 sulforafan 
               
               
                 Fursultiamin 
                 Cisapride 
                 tracazolate 
               
               
                 2-chloropyrazine 
                 Meptazinol 
                 verteporfin 
               
               
                 4′-N-benzoylstaurosporine 
                 eperisone 
                 atorvastatin 
               
               
                 estradiol 3-benzoate 
                 Acetaminophen 
                 tropisetron 
               
               
                 gibberellic acid 
                 oxolamine 
                 Etoposide 
               
               
                 Propidium 
                 phenothiazine 
                 Tropicamide 
               
               
                 Nafenopin 
                 Carbon Tetrachloride 
                 Nimodipine 
               
               
                 Noscapine 
                 Amitriptyline 
                 pramoxine 
               
               
                 Clomipramine 
                 Roxarsone 
                 pantoprazole 
               
               
                 Tetracycline 
                 Thiamphenicol 
                 Ondansetron 
               
               
                 Dicyclomine 
                 anastrozole 
                 oltipraz 
               
               
                 Tetanus Toxin 
                 Tiapamil Hydrochloride 
                 Miconazole 
               
               
                 Fluocinolone Acetonide 
                 acacetin 
                 heliotrine 
               
               
                 oxfendazole 
                 Hydroxyurea 
                 wortmannin 
               
               
                 Paroxetine 
                 bisphenol A 
                 dexibuprofen 
               
               
                 Etidronic Acid 
                 Nortriptyline 
                 Droperidol 
               
               
                 Ergocalciferols 
                 pioglitazone 
                 Lamivudine 
               
               
                 Metolazone 
                 Physostigmine 
                 Betaxolol 
               
               
                 Metoclopramide 
                 Raloxifene 
                 mycophenolate mofetil 
               
               
                 marimastat 
                 Cyclosporine 
                 Cholera Toxin 
               
               
                 Dexfenfluramine 
                 Cisplatin 
                 candesartan 
               
               
                 Y 27632 
                 Flupenthixol 
                 Chlorpheniramine 
               
               
                 Phenobarbital 
                 Doxazosin 
                 TO-901317 
               
               
                 Immunoglobulin M 
                 Chlortetracycline 
                 Kainic Acid 
               
               
                 Sulpiride 
                 Estradiol 
                 phenacemide 
               
               
                 Minoxidil 
                 ochratoxin A 
                 Luteolin 
               
               
                 Cimetidine 
                 Cholecalciferol 
                 Netilmicin 
               
               
                 Lithium Chloride 
                 Methimazole 
                 Trifluoperazine 
               
               
                 Bacitracin 
                 Amiloride 
                 Prazosin 
               
               
                 Fluphenazine 
                 Saquinavir 
                 Colchicine 
               
               
                 gefitinib 
                 Itraconazole 
                 Flavoxate 
               
               
                 Vincamine 
                 vanoxerine 
                 Triacetin 
               
               
                 Pemoline 
                 N,N′-diphenyl-4-phenylenediamine 
                 Gentamicins 
               
               
                 oxcarbazepine 
                 Losartan 
                 rabeprazole 
               
               
                 Azithromycin 
                 Clobetasol 
                 Clonazepam 
               
               
                 Thioacetamide 
                 nateglinide 
                 Asbestos 
               
               
                 Warfarin 
                 Amiodarone 
                 valdecoxib 
               
               
                 Altretamine 
                 Ramipril 
                 N-nitrosomorpholine 
               
               
                 lamotrigine 
                 rituximab 
                 zomepirac 
               
               
                 Furosemide 
                 Hydralazine 
                 Puromycin 
               
               
                 pirinixic acid 
                 Paclitaxel 
                 bromfenac 
               
               
                 Diethylhexyl Phthalate 
                 Aflatoxin B1 
                 Dexamethasone 
               
               
                 Ketoconazole 
                 Vinblastine 
                 Thioguanine 
               
               
                 Methylprednisolone 
                 U 0126 
                 Calcitriol 
               
               
                 bromobenzene 
                 Ethinyl Estradiol 
                 irinotecan 
               
               
                 Haloperidol 
                 Alpha-Amanitin 
                 Dactinomycin 
               
               
                 Vincristine 
                 Cycloheximide 
                 isoascorbic acid 
               
               
                 fluvastatin 
                 Tetradecanoylphorbol Acetate 
                   
               
            
           
           
               
            
               
                 R2. Molecules that downregulate SLC6A7: 
               
            
           
           
               
               
               
            
               
                 Nisoldipine 
                 Ethylene Glycol 
                 Nevirapine 
               
               
                 Promethazine 
                 Benzocaine 
                 PK 11195 
               
               
                 solasodine 
                 Hexachlorophene 
                 Penicillin G Benzathine 
               
               
                 Alprazolam 
                 Atenolol 
                 graveoline 
               
               
                 Ciprofloxacin 
                 lomefloxacin 
                 Mebendazole 
               
               
                 Nitrofurantoin 
                 Cyproterone 
                 Sulfinpyrazone 
               
               
                 Cefaclor 
                 flubendazole 
                 Melatonin 
               
               
                 Urethane 
                 N-Methylaspartate 
                 3,3′,4′,5-tetrachlorosalicylanilide 
               
               
                 Ifosfamide 
                 zopiclone 
                 Aminoglutethimide 
               
               
                 lead tetraacetate 
                 Glipizide 
                 Oxymetazoline 
               
               
                 Clofibric Acid 
                 sparfloxacin 
                 Chromium 
               
               
                 balsalazide 
                 Gentian Violet 
                 Etiocholanolone 
               
               
                 minaprine 
                 Mesna 
                 Penicillamine 
               
               
                 Thioctic Acid 
                 Trimethadione 
                 Promazine 
               
               
                 Omeprazole 
                 citiolone 
                 Hexetidine 
               
               
                 Indomethacin 
                 ipriflavone 
                 alpha-Amino-3-hydroxy-5- 
               
               
                   
                   
                 methyl-4-isoxazolepropionic Acid 
               
               
                 Aspirin 
                 methyl salicylate 
                 fenbufen 
               
               
                 Vecuronium Bromide 
                 Benzethonium 
                 levocabastine 
               
               
                 Acetazolamide 
                 closantel 
                 glimepiride 
               
               
                 chlorinated dibenzofurans 
                 Succinylcholine 
                 Busulfan 
               
               
                 Niacin 
                 Sulfamethoxazole 
                 Clotrimazole 
               
               
                 Carmustine 
                 Fonofos 
                 Procarbazine 
               
               
                 Cefotaxime 
                 Propylthiouracil 
                 Primaquine 
               
               
                 modafinil 
                 Tramadol 
                 Isoproterenol 
               
               
                 sodium selenate 
                 rofecoxib 
                 resveratrol 
               
               
                 Neomycin 
                 Enterotoxins 
                 artemether 
               
               
                 Clofazimine 
                 Acyclovir 
                 Rifampin 
               
               
                 Griseofulvin 
                 Methyltestosterone 
                 salicylamide 
               
               
                 chloroxylenol 
                 Pempidine 
                 letrozole 
               
               
                 celecoxib 
                 6-methoxy-2-naphthylacetic acid 
                 Diethylnitrosamine 
               
               
                 Ticlopidine 
                 Bromisovalum 
                 Atropine 
               
               
                 Isoflurophate 
                 torsemide 
                 Isoniazid 
               
               
                 dexchlorpheniramine 
                 Loratadine 
                 Carboplatin 
               
               
                 Cromolyn Sodium 
                 Ritonavir 
                 Mannitol 
               
               
                 Lomustine 
                 Vitamin E 
                 Sulfaphenazole 
               
               
                 Tocainide 
                 Iproniazid 
                 Tetrachlorodibenzodioxin 
               
               
                 Phenacetin 
                 tazobactam 
                 Cyclophosphamide 
               
               
                 Terazosin 
                 norethindrone acetate 
                 2-methoxyestradiol 
               
               
                 abamectin 
                 Azacitidine 
                 meloxicam 
               
               
                 geraniol 
                 2,3-dioxo-6-nitro-7- 
                 Soman 
               
               
                   
                 sulfamoylbenzo(f)quinoxaline 
                   
               
               
                 Debrisoquin 
                 Verapamil 
                 Methocarbamol 
               
               
                 acemetacin 
                 Amikacin 
                 ubiquinol 
               
               
                 Beclomethasone 
                 oxiconazole 
                 Biperiden 
               
               
                 Doxorubicin 
                 troglitazone 
                 Kanamycin 
               
               
                 Mefenamic Acid 
                 ozagrel 
                 enrofloxacin 
               
               
                 7-aminocephalosporanic acid 
                 Fenofibrate 
                 HI 6 
               
               
                 Chloroform 
                 Aminosalicylic Acid 
                 Cytarabine 
               
               
                 SC 514 
                 Tubocurarine 
                 nifuroxazide 
               
               
                 Zidovudine 
                 ONO 2235 
                 Praziquantel 
               
               
                 Chlorzoxazone 
                 Astemizole 
                 Safrole 
               
               
                 valacyclovir 
                 Fluoxetine 
                 Dipyridamole 
               
               
                 Bezafibrate 
                 4-nonylphenol 
                 Oxytetracycline 
               
               
                 clopidogrel 
                 lansoprazole 
                 Bleomycin 
               
               
                 venlafaxine 
                 telmisartan 
                 methylatropine 
               
               
                 idebenone 
                 Citalopram 
                 Gossypol 
               
               
                 Erythromycin 
                 1,5-naphthalenediamine 
                 meropenem 
               
               
                 Cinnarizine 
                 diphemanil methylsulfate 
                 Albendazole 
               
               
                 phthalylsulfathiazole 
                 Tranexamic Acid 
                 Estriol 
               
               
                 Cortisone 
                 artemisinine 
                 1-hydroxycholecalciferol 
               
               
                 tianeptine 
                 ethotoin 
                 Piperonyl Butoxide 
               
               
                 Norfloxacin 
                 Oxazepam 
                 Riluzole 
               
               
                 bromodichloromethane 
                 Aztreonam 
                 Nystatin 
               
               
                 Ethambutol 
                 2,2′-(hydroxynitrosohydrazono)bis- 
                 Spironolactone 
               
               
                   
                 ethanamine 
                   
               
               
                 4,4′-diaminodiphenylmethane 
                 Sertraline 
                 Naproxen 
               
               
                 Azlocillin 
                 gatifloxacin 
                 imiquimod 
               
               
                 Metronidazole 
                 Labetalol 
                 Diazepam 
               
               
                 zaleplon 
                 Nicotine 
                 Daunorubicin 
               
               
                 Azoxymethane 
                 Vancomycin 
                 Tranylcypromine 
               
               
                 enzastaurin 
                 Fludrocortisone 
                 lactacystin 
               
               
                 Maprotiline 
                 Pilocarpine 
                 Tacrine 
               
               
                 Mitoxantrone 
                 Cyproterone Acetate 
                 parthenolide 
               
               
                 Hydrogen Peroxide 
                 Methylcholanthrene 
                 Sirolimus 
               
               
                 quelamycin 
                 Pyrazinamide 
                 Pyrogallol 
               
               
                 Freund′s Adjuvant 
                 Poly I-C 
                 Doxepin 
               
               
                 Tamoxifen 
                 Prochlorperazine 
                 Piroxicam 
               
               
                 Diphenhydramine 
                 fomepizole 
                 Mestranol 
               
               
                 Tolbutamide 
                 Tolazamide 
                 Roxithromycin 
               
               
                 Genistein 
                 Triamterene 
                 imatinib 
               
               
                 Prednisone 
                 Carbimazole 
                 pralidoxime 
               
               
                 Fluorouracil 
                 Forskolin 
                 17-(allylamino)-17- 
               
               
                   
                   
                 demethoxygeldanamycin 
               
               
                 Tretinoin 
                 Thioridazine 
                 Levodopa 
               
               
                 Bupropion 
                 CPG-oligonucleotide 
                 Streptozocin 
               
               
                 Imipramine 
                 Ultraviolet Rays 
                 Melphalan 
               
               
                 rosiglitazone 
                 beta-Naphthoflavone 
                 quintozene 
               
               
                 Methotrexate 
                 Caffeine 
                 Epirubicin 
               
               
                 4-(5-benzo(1,3)dioxol-5-yl- 
                 Diclofenac 
                   
               
               
                 4-pyridin-2-yl-1H-imidazol-2-yl)benzamide 
                   
                   
               
            
           
           
               
            
               
                 S1. Molecules that upregulate DTNBP1: 
               
            
           
           
               
               
               
            
               
                 SC 514 
                 PK 11195 
                 Paraoxon 
               
               
                 Go 6976 
                 decitabine 
                 X-Rays 
               
               
                 Emetine 
                 Prostaglandins E 
                 Azacitidine 
               
               
                 Paclitaxel 
                 Dinoprostone 
                 norflurane 
               
               
                 benzyloxycarbonylleucyl- 
                 emtricitabine 
                 tetrafluoroethylene 
               
               
                 leucyl-leucine aldehyde 
                   
                   
               
               
                 shogaol 
                 procyanidin 
                 Promegestone 
               
               
                 Cytochalasin D 
                 temsirolimus 
                 Moxisylyte 
               
               
                 Mianserin 
                 iodoform 
                 Ethanol 
               
               
                 Levodopa 
                 Carcinogens 
                 Immunoglobulin M 
               
               
                 (melle-4)cyclosporin 
                 gatifloxacin 
                 tenofovir 
               
               
                 Staurosporine 
                 Antibodies, Monoclonal 
                 sapphyrin 
               
               
                 Ethionine 
                 bortezomib 
                 enrofloxacin 
               
               
                 Ecdysterone 
                 lenalidomide 
                 Sodium Dodecyl Sulfate 
               
               
                 2-(1H-indazol-4-yl)-6-(4- 
                 epoxomicin 
                 Estradiol 
               
               
                 methanesulfonylpiperazin- 
                   
                   
               
               
                 1-ylmethyl)-4-morpholin-4- 
                   
                   
               
               
                 ylthieno(3,2-d)pyrimidine 
                   
                   
               
               
                 Hemin 
                 Azithromycin 
                 Buspirone 
               
               
                 Carboplatin 
                 motexafin gadolinium 
                 BCG Vaccine 
               
               
                 monastrol 
                 Isoproterenol 
                 Disopyramide 
               
               
                 Inosine Monophosphate 
                 Cytochalasin B 
                 Antimycin A 
               
               
                 Ajmaline 
                 Sulpiride 
                 Amitriptyline 
               
               
                 1,3-dichlorobenzene 
                 systhane 
                 ascorbate-2-phosphate 
               
               
                 vorinostat 
                 8-((4-chlorophenyl)thio)cyclic-3′,5-AMP 
                 Ethionamide 
               
               
                 Spironolactone 
                 Nifedipine 
                 Tetrachlorodibenzodioxin 
               
               
                 Poly I-C 
                 Immunoglobulin G 
                 Methamphetamine 
               
               
                 mycophenolate mofetil 
                 Daunorubicin 
                 Tretinoin 
               
               
                 Doxepin 
                 Piperonyl Butoxide 
                 dasatinib 
               
               
                 acidocin CH5,  Lactobacillus   
                 GW 3965 
                 4-(5-benzo(1,3)dioxol-5-yl- 
               
               
                 
                   acidophilus 
                 
                   
                 4-pyridin-2-yl-1H-imidazol- 
               
               
                   
                   
                 2-yl)benzamide 
               
               
                 gefitinib 
                 CPG-oligonucleotide 
                 erlotinib 
               
               
                 U 0126 
                 everolimus 
                 peginterferon alfa-2a 
               
               
                 rituximab 
                 rosiglitazone 
                 cerivastatin 
               
               
                 letrozole 
                 atorvastatin 
                 benziodarone 
               
               
                 troglitazone 
                 gemcitabine 
                 bicalutamide 
               
               
                 norethindrone acetate 
                 HI 6 
                 nimesulide 
               
               
                 withaferin A 
                 lead acetate 
                 methylatropine 
               
               
                 arsenic trioxide 
                 geldanamycin 
                 Enalapril 
               
               
                 NG-Nitroarginine Methyl 
                 Bleomycin 
                 Triiodothyronine 
               
               
                 Ester 
                   
                   
               
               
                 Chitosan 
                 Cortisone 
                 Methylprednisolone 
               
               
                 Fluocinolone Acetonide 
                 Danazol 
                 Norethindrone 
               
               
                 Cyclosporine 
                 Imipramine 
                 Carbamazepine 
               
               
                 Methotrexate 
                 Genistein 
                 Quercetin 
               
               
                 Aflatoxin B1 
                 Rolipram 
                 Propylthiouracil 
               
               
                 Phenobarbital 
                 Tunicamycin 
                 Hydralazine 
               
               
                 Paroxetine 
                 Flunarizine 
                 Ranitidine 
               
               
                 Benzbromarone 
                 Clonidine 
                 Reserpine 
               
               
                 Quinidine 
                 Tolbutamide 
                 Chlorpropamide 
               
               
                 Acetylcysteine 
                 Pyrogallol 
                 Sarin 
               
               
                 Nitrofurantoin 
                 Haloperidol 
                 Ifosfamide 
               
               
                 Minocycline 
                 Doxycycline 
                 Idarubicin 
               
               
                 Sulindac 
                 Thapsigargin 
                 Amantadine 
               
               
                 Isotretinoin 
                 Diethylhexyl Phthalate 
                 Ascorbic Acid 
               
               
                 Azoxymethane 
                 Methapyrilene 
                 Metformin 
               
               
                 Flutamide 
                 Atenolol 
                 Cadmium 
               
            
           
           
               
            
               
                 S2. Molecules that downregulate DTNBP1: 
               
            
           
           
               
               
               
            
               
                 N (1)-methyl-2-lysergic acid diethylamide 
                 lysophosphatidic acid 
                 triptolide 
               
               
                 Nickel 
                 Diquat 
                 Terbutaline 
               
               
                 alpha-Amino-3-hydroxy-5-methyl- 
                 Nerve Growth Factors 
                 Propanil 
               
               
                 4-isoxazolepropionic Acid 
                   
                   
               
               
                 ubiquinol 
                 Melphalan 
                 bis(tri-n-butyltin)oxide 
               
               
                 Aphidicolin 
                 2-amino-1-methyl-6- 
                 Acetylmuramyl-Alanyl- 
               
               
                   
                 phenylimidazo(4,5-b)pyridine 
                 Isoglutamine 
               
               
                 CEP 14083 
                 Topotecan 
                 4-acetylaminofluorene 
               
               
                 Triazolam 
                 coumarin 
                 Ethambutol 
               
               
                 Camptothecin 
                 Ceftriaxone 
                 Theophylline 
               
               
                 R 848 
                 indole-3-carbinol 
                 Platelet Activating Factor 
               
               
                 8-aminohexylamino cAMP 
                 trichostatin A 
                 Alpha-Amanitin 
               
               
                 4-hydroxytamoxifen 
                 Pentachlorophenol 
                 7,8-Dihydro-7,8- 
               
               
                   
                   
                 dihydroxybenzo(a)pyrene 9,10- 
               
               
                   
                   
                 oxide 
               
               
                 1-(5-Isoquinolinesulfonyl)-2- 
                 Cisplatin 
                 Zinc Oxide 
               
               
                 Methylpiperazine 
                   
                   
               
               
                 n-hexanal 
                 Dihydrotestosterone 
                 Ibuprofen 
               
               
                 sangivamycin 
                 Acrolein 
                 Dactinomycin 
               
               
                 sulforafan 
                 naphthalan 
                 Growth Hormone 
               
               
                 Doxorubicin 
                 4-biphenylamine 
                 cobaltous chloride 
               
               
                 Cytokines 
                 shikonin 
                 Curcumin 
               
               
                 Colchicine 
                 cidofovir 
                 Sirolimus 
               
               
                 Tacrine 
                 Estrogens 
                 8-Bromo Cyclic Adenosine 
               
               
                   
                   
                 Monophosphate 
               
               
                 bevacizumab 
                 Cholera Toxin 
                 Acetaminophen 
               
               
                 Phosphorylcholine 
                 3-deazaneplanocin 
                 Phenacetin 
               
               
                 Dichlororibofuranosylbenzimidazole 
                 Potassium Dichromate 
                 Plicamycin 
               
               
                 quintozene 
                 CpG ODN 2216 
                 4-amino-6-hydrazino-7- 
               
               
                   
                   
                 beta-D-ribofuranosyl-7H- 
               
               
                   
                   
                 pyrrolo(2,3-d)-pyrimidine-5- 
               
               
                   
                   
                 carboxamide 
               
               
                 fasudil 
                 penciclovir 
                 Benzo(a)pyrene 
               
               
                 Dantrolene 
                 Vincristine 
                 ferric nitrilotriacetate 
               
               
                 Chorionic Gonadotropin 
                 Testosterone 
                 phenethyl isothiocyanate 
               
               
                 Hydrogel 
                 Insulin 
                 Acetazolamide 
               
               
                 N-nitrosomorpholine 
                 Pyrazinamide 
                 Isoniazid 
               
               
                 Caffeine 
                 Ultraviolet Rays 
                 Methyltestosterone 
               
               
                 Cephapirin 
                 SB 203580 
                 Lithium 
               
               
                 Brefeldin A 
                 N-methylpyrrolidone 
                 Rifampin 
               
               
                 1,2-dilinolenoyl-3-(4- 
                 Vehicle Emissions 
                 Tetradecanoylphorbol 
               
               
                 am inobutyryl)propane-1,2,3-triol 
                 Acetate 
                   
               
               
                 imatinib 
                 Dexamethasone 
                 Penicillamine 
               
               
                 Vancomycin 
                 Methylene Chloride 
                 Deferoxamine 
               
               
                 lapatinib 
                 dibenzazepine 
                 sunitinib 
               
               
                 Roflumilast 
                 17-(allylamino)-17- 
                   
               
               
                   
                 demethoxygeldanamycin 
                 infliximab 
               
               
                 lactacystin 
                 fluvastatin 
                 phosphonoacetamide 
               
               
                 2,3-dioxo-6-nitro-7- 
                 pioglitazone 
                 resveratrol 
               
               
                 sulfamoylbenzo(f)quinoxaline 
                   
                   
               
               
                 irinotecan 
                 4-nonylphenol 
                 terbinafine 
               
               
                 bromobenzene 
                 enterotoxin B, 
                 phenothiazine 
               
               
                   
                 staphylococcal 
                   
               
               
                 beta-glycerophosphoric acid 
                 AICA ribonucleotide 
                 oxaliplatin 
               
               
                 pralidoxime 
                 ochratoxin A 
                 bromodichloromethane 
               
               
                 closantel 
                 quelamycin 
                 sodium arsenite 
               
               
                 testosterone 17 beta-cypionate 
                 bisphenol A 
                 crotamiton 
               
               
                 Pyrogens 
                 Cardiotoxins 
                 Anti-Retroviral Agents 
               
               
                 Ribavirin 
                 Immunoglobulins, 
                 Antigen-Antibody 
               
               
                   
                 Intravenous 
                 Complex 
               
               
                 N-Methylaspartate 
                 Ionomyin 
                 Dinoprost 
               
               
                 Medroxyprogesterone Acetate 
                 Progesterone 
                 Prednisolone 
               
               
                 Cyproterone Acetate 
                 Chlormadinone 
                 Acetate Ergocalciferols 
               
               
                 Ciprofloxacin 
                 Oxyquinoline 
                 Indomethacin 
               
               
                 Luteolin 
                 beta-Naphthoflavone 
                 Diazepam 
               
               
                 Cycloheximide 
                 Hydroxyzine 
                 Fluconazole 
               
               
                 Miconazole 
                 Econazole 
                 Monocrotaline 
               
               
                 Azathioprine 
                 Chlormezanone 
                 Omeprazole 
               
               
                 Fluphenazine 
                 Chlorpromazine 
                 Mitomycin 
               
               
                 Bithionol 
                 Diethylnitrosamine 
                 Cyclophosphamide 
               
               
                 Chlorambucil 
                 Chloroform 
                 Carbon Tetrachloride 
               
               
                 Vitamin K 3 
                 Tetracycline 
                 Epirubicin 
               
               
                 Raloxifene 
                 Tamoxifen 
                 Diethylstilbestrol 
               
               
                 Lactic Acid 
                 Diclofenac 
                 Puromycin 
               
               
                   
                   
                 Aminonucleoside 
               
               
                 Aspirin 
                 Valproic Acid 
                 Disulfiram 
               
               
                 Mycophenolic Acid 
                 Fenofibrate 
                 Clofibrate 
               
               
                 Bezafibrate 
                 Atropine 
                 Tranylcypromine 
               
               
                 Methyldopa 
                 Guanethidine 
                 Sulfisoxazole 
               
               
                 Thioacetamide 
                 2-Acetylaminofluorene 
                 Formaldehyde 
               
               
                 Glycerol 
                 Lead 
                 Hydrogen Peroxide 
               
            
           
           
               
            
               
                 T1. Molecules that upregulate NDN: 
               
            
           
           
               
               
               
            
               
                 neuropeptide Y (18-36) 
                 perfosfamide 
                 decitabine 
               
               
                 naphthalene 
                 norflurane 
                 dibenzazepine 
               
               
                 trichostatin A 
                 Papaverine 
                 Cytochalasin D 
               
               
                 tyloxapol 
                 Methionine Sulfoximine 
                 mycophenolate mofetil 
               
               
                 Okadaic Acid 
                 Parathyroid Hormone 
                 beta-cyclodextrin-benzaldehyde 
               
               
                 Pivampicillin 
                 pelargonic acid 
                 Nocodazole 
               
               
                 Clodronic Acid 
                 lonidamine 
                 Tryptophan 
               
               
                 trichlorofluoromethane 
                 Botulinum Toxins, Type A 
                 fazarabine 
               
               
                 Edrophonium 
                 acodazole 
                 Tranylcypromine 
               
               
                 Dibucaine 
                 Riboflavin 
                 Tetanus Toxin 
               
               
                 Norepinephrine 
                 Tretinoin 
                 Ergocalciferols 
               
               
                 velnacrine 
                 diindolylmethane 
                 tetrahydrozoline 
               
               
                 Mianserin 
                 2,4-diaminotoluene 
                 amylocaine 
               
               
                 1-(2-cyano-3,12-dioxooleana-1,9-dien-28- 
                 tris(2,3-dibromopropyl)phosphate 
                 tetrafluoroethylene 
               
               
                 oyl) imidazole 
                   
                   
               
               
                 Puromycin 
                 telenzepine 
                 Isoproterenol 
               
               
                 Aminonucleoside 
                   
                   
               
               
                 Betazole 
                 midecamycin 
                 Cholera Toxin 
               
               
                 N-Methylscopolamine 
                 Rolitetracycline 
                 temsirolimus 
               
               
                 Triprolidine 
                 Fursultiamin 
                 CPG-oligonucleotide 
               
               
                 Talampicillin 
                 Triflupromazine 
                 LPS 9 
               
               
                 1-amino-2,4- 
                 Glycerol 
                 dironyl 
               
               
                 dibromoanthraquinone 
                   
                   
               
               
                 Isoxsuprine 
                 Vitamin B 12 
                 hydrocotarnine 
               
               
                 Estrone 
                 Khellin 
                 Dextran Sulfate 
               
               
                 Cardiotoxins 
                 solasodine 
                 Doxorubicin 
               
               
                 Sirolimus 
                 oltipraz 
                 iodoform 
               
               
                 2-methoxyestradiol 
                 letrozole 
                 Dimethyl Sulfoxide 
               
               
                 dasatinib 
                 Hydrogen Peroxide 
                 Epirubicin 
               
               
                 sertaconazole 
                 Bupropion 
                 gram me 
               
               
                 Pregnenolone 
                 Amitriptyline 
                 1-ethyl-2-benzimidazolinone 
               
               
                 Cinnarizine 
                 delsoline 
                 Spiramycin 
               
               
                 MF59 oil emulsion 
                 Triamterene 
                 Lynestrenol 
               
               
                 ferric nitrilotriacetate 
                 Cyclophosphamide 
                 Bisoprolol 
               
               
                 sulforafan 
                 fenbufen 
                 Tacrine 
               
               
                 Propidium 
                 efavirenz 
                 sunitinib 
               
               
                 phenethyl isothiocyanate 
                 docetaxel 
                 Roxarsone 
               
               
                 17-(dimethylaminoethylamino)- 
                 Vitamin E 
                 Azacitidine 
               
               
                 17-demethoxygeldanamycin 
                   
                   
               
               
                 Albuterol 
                 Calcitriol 
                 Imipramine 
               
               
                 Rifampin 
                 aluminum sulfate 
                 Heparin 
               
               
                 Sulfamerazine 
                 Bacitracin 
                 resveratrol 
               
               
                 acemetacin 
                 bis(tri-n-butyltin)oxide 
                 heliotrine 
               
               
                 Ethambutol 
                 cinchonine 
                 acidocin CH5,  Lactobacillus   
               
               
                   
                   
                 
                   acidophilus 
                 
               
               
                 Diethylhexyl Phthalate 
                 Atropine 
                 Diazinon 
               
               
                 N-methylpyrrolidone 
                 Lamivudine 
                 Allopurinol 
               
               
                 Dapsone 
                 Nicotine 
                 fulvestrant 
               
               
                 phosphonoacetamide 
                 Cytokines 
                 Paclitaxel 
               
               
                 Amoxapine 
                 Progesterone 
                 Allantoin 
               
               
                 Fenbendazole 
                 GW 3965 
                 Mifepristone 
               
               
                 Dimethylnitrosamine 
                 Betahistine 
                 Flavoxate 
               
               
                 Fenoprofen 
                 fluticasone 
                 lapatinib 
               
               
                 Androsterone 
                 Cisplatin 
                 Hydralazine 
               
               
                 diflorasone diacetate 
                 Alpha-Amanitin 
                 Ethanol 
               
               
                 Acetaminophen 
                 Galantamine 
                 N-nitrosomorpholine 
               
               
                 gemcitabine 
                 sulconazole 
                 Pergolide 
               
               
                 2-(4-morpholinyl)-8-phenyl- 
                 Propylthiouracil 
                 Sulfadiazine 
               
               
                 4H-1-benzopyran-4-one 
                   
                   
               
               
                 Pregnenolone Carbonitrile 
                 Methimazole 
                 Dactinomycin 
               
               
                 Tetracycline 
                 aristolochic acid I 
                 Isotretinoin 
               
               
                 Inosine Monophosphate 
                 Doxycycline 
                 Fluorouracil 
               
               
                 Ultraviolet Rays 
                 gefitinib 
                 Dinoprostone 
               
               
                 Norethindrone 
                 Cytarabine 
                 Carboplatin 
               
               
                 Etoposide 
                 Sulindac 
                 Raloxifene 
               
               
                 Tamoxifen 
                 Metformin 
                   
               
            
           
           
               
            
               
                 T2. Molecules that upregulate NDN: 
               
            
           
           
               
               
               
            
               
                 scriptaid 
                 apicidin 
                 X-Rays 
               
               
                 shikonin 
                 Cefoperazone 
                 Natriuretic Peptide, C-Type 
               
               
                 quintozene 
                 Methylene Chloride 
                 monophosphoryl lipid A 
               
               
                 Pindolol 
                 2,2′-Dipyridyl 
                 2,4-Dinitrophenol 
               
               
                 Enterotoxins 
                 Ethylene Oxide 
                 naphthalan 
               
               
                 vanadium pentoxide 
                 Estrogens, Conjugated (USP) 
                 vorinostat 
               
               
                 ranolazine 
                 Emodin 
                 TO-901317 
               
               
                 4,4′-diaminodiphenylmethane 
                 Pyrazinamide 
                 Etidronic Acid 
               
               
                 Piperonyl Butoxide 
                 N-Methylaspartate 
                 Anti-Retroviral Agents 
               
               
                 Cymarine 
                 Fusidic Acid 
                 Ozone 
               
               
                 Ethylene Dibromide 
                 enterotoxin B, staphylococcal 
                 VX 
               
               
                 Butyric Acid 
                 Fonofos 
                 Deoxycholic Acid 
               
               
                 testosterone 17 beta-cypionate 
                 Rotenone 
                 1,2,3-trichloropropane 
               
               
                 Thiethylperazine 
                 Ampicillin 
                 Shiga Toxin 
               
               
                 Trichloroepoxypropane 
                 1-Methyl-3-isobutylxanthine  
                 Parathion 
               
               
                 chlorinated dibenzofurans 
                 isoconazole 
                 ceforanide 
               
               
                 Phenobarbital 
                 Immunoglobulins, Intravenous 
                 Abscisic Acid 
               
               
                 Fluocinolone Acetonide 
                 alpha-Amino-3-hydroxy-5- 
                 Methylnitrosourea 
               
               
                   
                 methyl-4-isoxazolepropionic Acid 
                   
               
               
                 Phosgene 
                 direct black 3 
                 perfluorooctane sulfonic acid 
               
               
                 iturelix 
                 Dexfenfluramine 
                 Hydrocortisone 
               
               
                 beta-glycerophosphoric acid 
                 infliximab 
                 lactacystin 
               
               
                 valdecoxib 
                 rosiglitazone 
                 Creatine 
               
               
                 Ranitidine 
                 Risperidone 
                 1-Methyl-4-phenyl-1,2,3,6- 
               
               
                   
                   
                 tetrahydropyridine 
               
               
                 Benzo(a)pyrene 
                 benzyloxycarbonylleucyl- 
                 everolimus 
               
               
                   
                 leucyl-leucine aldehyde 
                   
               
               
                 Acrolein 
                 Terfenadine 
                 R848 
               
               
                 ubiquinol 
                 Thapsigargin 
                 Insulin 
               
               
                 Chitosan 
                 Metolazone 
                 temozolomide 
               
               
                 Chorionic Gonadotropin 
                 Azoxymethane 
                 Phytohemagglutinins 
               
               
                 Isoniazid 
                 cyclobenzaprine 
                 Cyproterone Acetate 
               
               
                 4-biphenylamine 
                 Bleomycin 
                 Y 27632 
               
               
                 6-methoxy-2-naphthylacetic acid 
                 Paroxetine 
                 Calcium 
               
               
                 Dexamethasone 
                 Ascorbic Acid 
                 4-O-methyl-12-O- 
               
               
                   
                   
                 tetradecanoylphorbol 13-acetate 
               
               
                 halofuginone 
                 Testosterone 
                 Hydrochloric Acid 
               
               
                 Cyproheptadine 
                 Enalapril 
                 Ouabain 
               
               
                 Urethane 
                 Chlorpropamide 
                 Gonadotropins 
               
               
                 Moclobemide 
                 Diethylstilbestrol 
                 linezolid 
               
               
                 Dinitrofluorobenzene 
                 Vehicle Emissions 
                 Corticosterone 
               
               
                 LBH589 
                 dexchlorpheniramine 
                 Valproic Acid 
               
               
                 mono-(2-ethylhexyl)phthalate 
                 imatinib 
                 Lithium 
               
               
                 Pyrogens 
                 4-dichlorobenzene 
                 alginic acid 
               
               
                 Medroxyprogesterone Acetate 
                 Carbamazepine 
                 Deoxyglucose 
               
               
                 Benzethonium 
                 Cefuroxime 
                 Lactic Acid 
               
               
                 4-hydroxy-2-nonenal 
                 Mitoxantrone 
                 isoascorbic acid 
               
               
                 Captopril 
                 Propofol 
                 Estradiol 
               
               
                 Tolbutamide 
                 Tetrachlorodibenzodioxin 
                 U 0126 
               
               
                 Methylprednisolone 
                 Phenacetin 
                 Loratadine 
               
               
                 tenofovir 
                 Dinoprost 
                 Forskolin 
               
               
                 Quercetin 
                 Tetradecanoylphorbol Acetate 
                 glimepiride 
               
               
                 4-(5-benzo(1,3)dioxol-5-yl- 
                 Vancomycin 
                 Cycloheximide 
               
               
                 4-pyridin-2-yl-1H-imidazol- 
                   
                   
               
               
                 2-yl)benzamide 
                   
                   
               
               
                 Azauridine 
                 Caffeine 
                 Methyl Methanesulfonate 
               
               
                 Tunicamycin 
                 Monocrotaline 
                 Fluoxetine 
               
               
                 Chlormadinone Acetate 
                 Metronidazole 
                 Betamethasone 
               
               
                 Ethinyl Estradiol 
                 Methotrexate 
                 Bucladesine 
               
               
                 Ethionine 
                 Folic Acid 
                 atorvastatin 
               
               
                 Amiodarone 
                 sodium arsenite 
                 hydrazine 
               
               
                 Prednisolone 
                 Genistein 
                 Lovastatin 
               
               
                 Trimethadione 
                 gatifloxacin 
                 Diazepam 
               
               
                 bortezomib 
                 Fenofibrate 
                 Nitrofurantoin 
               
               
                 Diethylnitrosamine 
                 Neomycin 
                 BCG Vaccine 
               
               
                 Ethionamide 
                 fluvastatin 
                 pioglitazone 
               
               
                 troglitazone 
                 leflunomide 
                 bisphenol A 
               
               
                 Poly I-C 
                 Ionomyin 
                 Epitestosterone 
               
               
                 Cyclosporine 
                 Indomethacin 
                 Miconazole 
               
               
                 Vincristine 
                 Colchicine 
                 Chlorpromazine 
               
               
                 Azithromycin 
                 Carbon Tetrachloride 
                 Ibuprofen 
               
               
                 Diclofenac 
                 Gemfibrozil 
                 Bezafibrate 
               
               
                 Thioacetamide 
                   
                   
               
            
           
           
               
            
               
                 U1. Molecules that upregulate TP53: 
               
            
           
           
               
               
               
            
               
                 sangivamycin 
                 4-amino-6-hydrazino-7- 
                 Curcumin 
               
               
                   
                 beta-D-ribofuranosyl-7H- 
                   
               
               
                   
                 pyrrolo(2,3-d)-pyrimidine-5-carboxamide 
                   
               
               
                 pirlindole 
                 Paclitaxel 
                 Piroxicam 
               
               
                 Ethionine 
                 Mannitol 
                 versipelostatin 
               
               
                 Caerulein 
                 2-Acetylaminofluorene 
                 Ethylene Oxide 
               
               
                 Dimethylnitrosamine 
                 Acetylmuramyl-Alanyl-Isoglutamine 
                 sapphyrin 
               
               
                 Foscarnet 
                 Sulfisoxazole 
                 Dicloxacillin 
               
               
                 4-(N-methyl-N- 
                 Cefmetazole 
                 Diclofenac 
               
               
                 nitrosamino)-1-(3-pyridyl)-1-butanone 
                   
                   
               
               
                 isoxicam 
                 Go 6976 
                 thiocolchicoside 
               
               
                 Oxytocin 
                 Plicamycin 
                 tranilast 
               
               
                 alphaxalone 
                 Moricizine 
                 Fluorouracil 
               
               
                 1-hydroxycholecalciferol 
                 1-Methyl-4-phenyl-1,2,3,6- 
                 Diethylhexyl Phthalate 
               
               
                   
                 tetrahydropyridine 
                   
               
               
                 Idoxuridine 
                 Mitomycin 
                 hexachlorobutadiene 
               
               
                 Viomycin 
                 phenoclor 
                 Gentamicins 
               
               
                 benoxaprofen 
                 Zalcitabine 
                 Isoniazid 
               
               
                 Estradiol 
                 lead tetraacetate 
                 Midodrine 
               
               
                 Pyrazinamide 
                 naphthalene 
                 Nickel 
               
               
                 Spironolactone 
                 Amiodarone 
                 Emetine 
               
               
                 Ethynodiol Diacetate 
                 Phenobarbital 
                 Oxyquinoline 
               
               
                 Thioacetamide 
                 bisphenol A 
                 PI103 
               
               
                 flumequine 
                 estradiol 3-benzoate 
                 Methylene Chloride 
               
               
                 Vecuronium Bromide 
                 apratoxin A 
                 Phytohemagglutinins 
               
               
                 Benzo(a)pyrene 
                 glycitein 
                 lornoxicam 
               
               
                 motexafin gadolinium 
                 Benzethonium 
                 Y 27632 
               
               
                 Yellow Fever Vaccine 
                 fasudil 
                 Netilmicin 
               
               
                 flavanone 
                 Nifedipine 
                 Histidinol 
               
               
                 (melle-4)cyclosporin 
                 Ethambutol 
                 Naproxen 
               
               
                 Ketorolac 
                 eseroline 
                 testosterone 17 beta-cypionate 
               
               
                 Megestrol Acetate 
                 Acrolein 
                 hydrastine 
               
               
                 pipenzolate 
                 Methylcholanthrene 
                 Aristolochic Acids 
               
               
                 Cyclosporine 
                 Diethylnitrosamine 
                 Furosemide 
               
               
                 Methimazole 
                 Nordefrin 
                 aceclofenac 
               
               
                 Oxytetracycline 
                 Sulfaphenazole 
                 phenacemide 
               
               
                 Aconitine 
                 Ethionamide 
                 Methyldopa 
               
               
                 Molsidomine 
                 Botulinum Toxins 
                 Orotic Acid 
               
               
                 1,3-dichlorobenzene 
                 Malathion 
                 phenothiazine 
               
               
                 daidzein 
                 Cephapirin 
                 temafloxacin 
               
               
                 artemisinine 
                 Botulinum Toxins, Type A 
                 Tunicamycin 
               
               
                 piclamilast 
                 Didanosine 
                 Roflumilast 
               
               
                 Epitestosterone 
                 Soman 
                 Metformin 
               
               
                 Cefoxitin 
                 Nom ifensine 
                 hexachloroethane 
               
               
                 sulfathiazole 
                 4-octylphenol 
                 Methotrexate 
               
               
                 deferiprone 
                 Mebendazole 
                 quintozene 
               
               
                 Nitrofurazone 
                 Dihydrotestosterone 
                 sodium arsenite 
               
               
                 Sulfadoxine 
                 Betamethasone 
                 ethamivan 
               
               
                 monophosphoryl lipid A 
                 Lomustine 
                 erlotinib 
               
               
                 Enalapril 
                 Ranitidine 
                 Clotrimazole 
               
               
                 triptolide 
                 Rifampin 
                 Bupropion 
               
               
                 Acetylcysteine 
                 lactacystin 
                 direct black 3 
               
               
                 HI 6 
                 nateglinide 
                 1,5-naphthalenediamine 
               
               
                 tris(2,3-dibromopropyl)phosphate 
                 Quinpirole 
                 sildenafil 
               
               
                 Captopril 
                 Vitamin E 
                 nimesulide 
               
               
                 lead acetate 
                 Ribostamycin 
                 sodium selenate 
               
               
                 Methapyrilene 
                 Disulfiram 
                 Tetradecanoylphorbol Acetate 
               
               
                 Monocrotaline 
                 Tryptophan 
                 Forskolin 
               
               
                 Mifepristone 
                 Risperidone 
                 Ganciclovir 
               
               
                 polidocanol 
                 Remoxipride 
                 beta-cyclodextrin-benzaldehyde 
               
               
                 N-Ac-CHAVC-NH2 
                 Abscisic Acid 
                 isopyrin 
               
               
                 Metribolone 
                 6-azathymine 
                 Azacitidine 
               
               
                 benazepril 
                 Bethanechol 
                 Famotidine 
               
               
                 Vancomycin 
                 diisopropyl methylphosphonate 
                 Ethylene Dibromide 
               
               
                 Fluspirilene 
                 atorvastatin 
                 iodoform 
               
               
                 7,8-Dihydro-7,8- 
                 Oxyphenisatin Acetate 
                 1-amino-2,4- 
               
               
                 dihydroxybenzo(a)pyrene 9,10-oxide 
                   
                 dibromoanthraquinone 
               
               
                 Ionidamine 
                 Pinacidil 
                 methylatropine 
               
               
                 Estriol 
                 Melphalan 
                 cephaelin 
               
               
                 Pirenzepine 
                 Altretamine 
                 beta-Naphthoflavone 
               
               
                 alpha-Amino-3-hydroxy-5- 
                 Cadmium  
                 Mesna 
               
               
                 methyl-4-isoxazolepropionic Acid 
                   
                   
               
               
                 Bithionol 
                 Ibuprofen 
                 Nafronyl 
               
               
                 Tolazoline 
                 Sotalol 
                 Muromonab-CD3 
               
               
                 Calcitriol 
                 amitraz 
                 Amphotericin B 
               
               
                 Cholecalciferol 
                 Sulbactam 
                 Insulin 
               
               
                 Beclomethasone 
                 Cardiotoxins 
                 Azlocillin 
               
               
                 SU 5416 
                 Selenomethionine 
                 oxcarbazepine 
               
               
                 Kanamycin 
                 Lithium 
                 Etodolac 
               
               
                 1,2,3-trichloropropane 
                 Mephenytoin 
                 Clarithromycin 
               
               
                 Carboplatin 
                 Chlorpromazine 
                 Enoxacin 
               
               
                 Azithromycin 
                 modafinil 
                 Cyproterone Acetate 
               
               
                 hydroxytamoxifen 
                 Moxalactam 
                 Ciprofloxacin 
               
               
                 Milrinone 
                 Miconazole 
                 rituximab 
               
               
                 Ethinyl Estradiol 
                 Aminosalicylic Acid 
                 6-Mercaptopurine 
               
               
                 Freund′s Adjuvant 
                 CpG ODN 2216 
                 Methyltestosterone 
               
               
                 Cyclophosphamide 
                 Busulfan 
                 nabumetone 
               
               
                 Harmaline 
                 Diflunisal 
                 Lincomycin 
               
               
                 Azathioprine 
                 Cyclopenthiazide 
                 Stavudine 
               
               
                 N, N′-diphenyl-4- 
                 Rolipram 
                 Phenylalanine 
               
               
                 phenylenediamine 
                   
                   
               
               
                 ONO 2235 
                 celecoxib 
                 4-hydroxy-2-nonenal 
               
               
                 Sulindac 
                 lamotrigine 
                 Ketoprofen 
               
               
                 Indomethacin 
                 Digoxin 
                 Cytarabine 
               
               
                 Baclofen 
                 fluvastatin 
                 cilostazol 
               
               
                 Nordihydroguaiaretic Acid 
                 Amphetamine 
                 Penicillamine 
               
               
                 Nystatin 
                 temozolomide 
                 dibenzazepine 
               
               
                 linezolid 
                 lacidipine 
                 flavopiridol 
               
               
                 acadesine 
                 olanzapine 
                 Hydroxyurea 
               
               
                 Nevirapine 
                 Chlorpyrifos 
                 Acetazolamide 
               
               
                 Streptomycin 
                 Niacin 
                 ciprofibrate 
               
               
                 Flupenthixol 
                 Econazole 
                 Allopurinol 
               
               
                 17-(allylamino)-17-demethoxygeldanamycin 
                 Amlodipine 
                 2,2′-Dipyridyl 
               
               
                 Nicotine 
                 Nitrendipine 
                 Neomycin 
               
               
                 edelfosine 
                 Mycophenolic Acid 
                 Fluphenazine 
               
               
                 Sumatriptan 
                 canadine 
                 Edrophonium 
               
               
                 acetovanillone 
                 Doxazosin 
                 Domperidone 
               
               
                 Atropine 
                 N-Methylaspartate 
                 Fluconazole 
               
               
                 Lovastatin 
                 mono-(2-ethylhexyl)phthalate 
                 U 0126 
               
               
                 Dexfenfluramine 
                 alpha-Tocopherol 
                 Methazolamide 
               
               
                 Ketoconazole 
                 desloratadine 
                 Aphidicolin 
               
               
                 Quercetin 
                 Citalopram 
                 Nadolol 
               
               
                 Podophyllotoxin 
                 Perhexiline 
                 leflunomide 
               
               
                 ferulic acid 
                 lansoprazole 
                 MRK 003 
               
               
                 pirinixic acid 
                 Omeprazole 
                 Papaverine 
               
               
                 Vinblastine 
                 Kainic Acid 
                 Luteolin 
               
               
                 4-(5-benzo(1,3)dioxol-5-yl- 
                 Lisinopril 
                 Staurosporine 
               
               
                 4-pyridin-2-yl-1H-imidazol-2-yl)benzamide 
                   
                   
               
               
                 Nimodipine 
                 NG-Nitroarginine Methyl Ester 
                 tenofovir 
               
               
                 Finasteride 
                 Levodopa 
                 Paroxetine 
               
               
                 carvedilol 
                 Aminoglutethimide 
                 Terbutaline 
               
               
                 Imipramine 
                 Clonazepam 
                 Pregnenolone Carbonitrile 
               
               
                 anastrozole 
                 pralidoxime 
                   
               
            
           
           
               
            
               
                 U2. Molecules that downregulate TP53: 
               
            
           
           
               
               
               
            
               
                 Cycloserine 
                 monastrol 
                 JM 3100 
               
               
                 nilutamide 
                 Aclarubicin 
                 1-(5-Isoquinolinesulfonyl)-2- 
               
               
                   
                   
                 Methylpiperazine 
               
               
                 blebbistatin 
                 Vincristine 
                 LBH589 
               
               
                 geldanamycin 
                 N-benzyladenine 
                 tridihexethyl 
               
               
                 Dimethyl Sulfoxide 
                 cyanoginosin LR 
                 buflomedil 
               
               
                 4-acetylaminofluorene 
                 trichostatin A 
                 apicidin 
               
               
                 Coumaphos 
                 Cefotiam 
                 PK 11195 
               
               
                 Prilocaine 
                 HC toxin 
                 Biotin 
               
               
                 scriptaid 
                 Butyric Acid 
                 Deoxycholic Acid 
               
               
                 Piracetam 
                 4,4′-diam inodiphenylmethane 
                 Immunoglobulin M 
               
               
                 Histamine 
                 decitabine 
                 Suppressor Factors, Immunologic 
               
               
                 Doxycycline 
                 Amikacin 
                 Primaquine 
               
               
                 bafilomycin A 
                 Debrisoquin 
                 7-aminocephalosporanic acid 
               
               
                 DDT 
                 phenylhydrazine 
                 Etiocholanolone 
               
               
                 Simazine 
                 4-biphenylamine 
                 Asbestos 
               
               
                 Mycotoxins 
                 3-deazaneplanocin 
                 8-aminohexylamino cAMP 
               
               
                 9-(2-hydroxy-3-nonyl)adenine 
                 Chlordiazepoxide 
                 Theophylline 
               
               
                 anisindione 
                 Reserpine 
                 geraniol 
               
               
                 Bromhexine 
                 Dobutamine 
                 2-(4-morpholinoanilino)-6- 
               
               
                   
                   
                 cyclohexylaminopurine 
               
               
                 Piperonyl Butoxide 
                 kavain 
                 abamectin 
               
               
                 pimethixene 
                 bromodichloromethane 
                 Sirolimus 
               
               
                 halofuginone 
                 Probucol 
                 Clorgyline 
               
               
                 Vitamin B 12 
                 Tetanus Toxin 
                 ochratoxin A 
               
               
                 Procainamide 
                 diphenidol 
                 cidofovir 
               
               
                 compactin 
                 Growth Hormone 
                 Promegestone 
               
               
                 Antibodies, Monoclonal 
                 Bismuth 
                 Ofloxacin 
               
               
                 Eugenol 
                 Ergocalciferols 
                 Citric Acid 
               
               
                 1-ethyl-2-benzimidazolinone 
                 N-Methyl-3,4-methylenedioxyamphetamine 
                 Doxapram 
               
               
                 Sparteine 
                 adiphenine 
                 Aflatoxin B1 
               
               
                 Valproic Acid 
                 Sulfamonomethoxine 
                 Cholera Toxin 
               
               
                 Amoxapine 
                 Cycloheximide 
                 Acetaminophen 
               
               
                 cineole 
                 Phenol 
                 Doxorubicin 
               
               
                 Hydrocortisone 
                 quelamycin 
                 doxofylline 
               
               
                 Sodium Dodecyl Sulfate 
                 vinclozolin 
                 Antimycin A 
               
               
                 Lamivudine 
                 Nitric Oxide 
                 Fluoxetine 
               
               
                 Ethacrynic Acid 
                 Flavoxate 
                 Guanethidine 
               
               
                 Dactinomycin 
                 Lindane 
                 vorinostat 
               
               
                 Zinc Oxide 
                 Triacetin 
                 Methylnitrosourea 
               
               
                 clinafloxacin 
                 rifapentine 
                 CPG-oligonucleotide 
               
               
                 phensuximide 
                 Disopyramide 
                 benfluorex 
               
               
                 Methoxsalen 
                 Flufenamic Acid 
                 Fusaric Acid 
               
               
                 Carcinogens 
                 irinotecan 
                 4-dichlorobenzene 
               
               
                 Tacrine 
                 Chlorpropamide 
                 Tetracycline 
               
               
                 Anti-Retroviral Agents 
                 Azaperone 
                 eburnamonine 
               
               
                 methiazole 
                 Cam ptothecin 
                 Carbimazole 
               
               
                 Buspirone 
                 aluminum sulfate 
                 Erythromycin 
               
               
                 vinylidene chloride 
                 Diltiazem 
                 tosufloxacin 
               
               
                 rauwolscine-OHPC 
                 Buform in 
                 pioglitazone 
               
               
                 temsirolimus 
                 Chloroquine 
                 Colchicine 
               
               
                 Ethyl Methanesulfonate 
                 Lidocaine 
                 Prochlorperazine 
               
               
                 Nitrofurantoin 
                 Etidronic Acid 
                 Caffeine 
               
               
                 Terazosin 
                 Prednisolone 
                 Dexamethasone 
               
               
                 Moxisylyte 
                 Amiloride 
                 dexamisole 
               
               
                 Alprazolam 
                 Medroxyprogesterone 
                 Daunorubicin 
               
               
                 Fenbendazole 
                 Deoxyglucose 
                 methyl salicylate 
               
               
                 Zidovudine 
                 Ticlopidine 
                 Fluocinolone Acetonide 
               
               
                 enzastaurin 
                 Procaine 
                 Chlorambucil 
               
               
                 oxybenzone 
                 Lactic Acid 
                 1,1,1-trichloroethane 
               
               
                 Diazinon 
                 Flunarizine 
                 Genistein 
               
               
                 interferon alfa-2b 
                 Pyrilamine 
                 Clomipramine 
               
               
                 romidepsin 
                 oxiconazole 
                 Clofibric Acid 
               
               
                 4-methyl-N-(3-(4-methylimidazol-1-yl)-5- 
                 meloxicam 
                 Clemastine 
               
               
                 (trifluoromethyl)phenyl)-3-((4-pyridin-3- 
                   
                   
               
               
                 ylpyrimidin-2-yl)amino)benzamide 
                   
                   
               
               
                 Haloperidol 
                 bis(tri-n-butyltin)oxide 
                 Dothiepin 
               
               
                 Metoprolol 
                 shogaol 
                 Aminocaproic Acids 
               
               
                 8-Bromo Cyclic Adenosine Monophosphate 
                 n-hexanal 
                 Clofibrate 
               
               
                 Chlorpheniramine 
                 Etoposide 
                 hexylcaine 
               
               
                 Dantrolene 
                 Methylprednisolone 
                 resveratrol 
               
               
                 Alpha-Amanitin 
                 epoxomicin 
                 colforsin 
               
               
                 Ascorbic Acid 
                 Folic Acid 
                 Safrole 
               
               
                 loxoprofen 
                 Dimethylformamide 
                 securinine 
               
               
                 letrozole 
                 ranolazine 
                 adalimumab 
               
               
                 X-Rays 
                 Atenolol 
                 Clonidine 
               
               
                 naringin 
                 Verapamil 
                 Phenacetin 
               
               
                 vinpocetine 
                 gabapentin 
                 Topotecan 
               
               
                 Dipyridamole 
                 Nifurtimox 
                 Pergolide 
               
               
                 Losartan 
                 Alendronate 
                 Gemfibrozil 
               
               
                 Promazine 
                 tianeptine 
                 Hexachlorophene 
               
               
                 Loratadine 
                 bortezomib 
                 1,10-phenanthroline 
               
               
                 Oxymetazoline 
                 candesartan 
                 Azaguanine 
               
               
                 Inosine Monophosphate 
                 pantoprazole 
                 Granisetron 
               
               
                 Pentolinium Tartrate 
                 efavirenz 
                 Ifosfamide 
               
               
                 Methyl Methanesulfonate 
                 sorafenib 
                 Doxepin 
               
               
                 cerivastatin 
                 2-(4-morpholinyl)-8-phenyl-4H-1- 
                 Phenylephrine 
               
               
                   
                 benzopyran-4-one 
                   
               
               
                 Propidium 
                 Mesoridazine 
                 ebselen 
               
               
                 Aspirin 
                 Dichlororibofuranosylbenzimidazole 
                 Deferoxamine 
               
               
                 VX 
                 Gallamine Triethiodide 
                 Isoflurophate 
               
               
                 Clozapine 
                 imatinib 
                 Norepinephrine 
               
               
                 Nocodazole 
                 Metergoline 
                 Rotenone 
               
               
                 tropisetron 
                 Simvastatin 
                 Mianserin 
               
               
                 ebastine 
                 Sarin 
                 Sulpiride 
               
               
                 Propranolol 
                 Gabexate 
                 Thioridazine 
               
               
                 Clindamycin 
                 3,3′,4′,5-tetrachlorosalicylanilide 
                 Indinavir 
               
               
                 Dimenhydrinate 
                 1-Methyl-3-isobutylxanthine 
                 Ribavirin 
               
               
                 Brefeldin A 
                 Pravastatin 
                 zaleplon 
               
               
                 Dicumarol 
                 valdecoxib 
                 Terfenadine 
               
               
                 Phenelzine 
                 Timolol 
                 Melatonin 
               
               
                 Carmustine 
                 fragment C, human serum albumin  
                 Diazepam 
               
               
                 Chloramphenicol 
                 Nitrazepam 
                 Shiga Toxin 
               
               
                 Isoproterenol 
                 2-methoxyestradiol 
                 Amitriptyline 
               
               
                 Fluvoxamine 
                 phosphonoacetamide 
                 isoascorbic acid 
               
               
                 clopidogrel 
                 2,3-dioxo-6-nitro-7- 
                 Albendazole 
               
               
                   
                 sulfamoylbenzo(f)quinoxaline 
                   
               
               
                 Labetalol 
                 Maprotiline 
                 Choline 
               
               
                 Trihexyphenidyl 
                 zileuton 
                 Propylthiouracil 
               
               
                 rofecoxib 
                 venlafaxine 
                 Ionomyin 
               
               
                 SU 5402 
                 Tocainide 
                 Ramipril 
               
               
                 Bezafibrate 
                 Flurbiprofen 
                 oxybutynin 
               
               
                 dasatinib 
                 gemcitabine 
                 gefitinib 
               
               
                 Tranylcypromine 
                 Sertraline 
                 Thioguanine 
               
               
                 Vitamin K 3 
                 Promethazine 
                   
               
            
           
           
               
            
               
                 V1. Molecules that upregulate PPAR-y: 
               
            
           
           
               
               
               
            
               
                 rosiglitazone 
                 1,5-naphthalenediamine 
                 2-(4-morpholinyl)-8-phenyl- 
               
               
                   
                   
                 4H-1-benzopyran-4-one 
               
               
                 N, N′-diphenyl-4-phenylenediamine 
                 Dimaprit 
                 Lithocholic Acid 
               
               
                 Ethylestrenol 
                 Tolazamide 
                 benphothiamine 
               
               
                 1,3-dichlorobenzene 
                 compactin 
                 artemether 
               
               
                 Spironolactone 
                 Brom hexine 
                 amineptin 
               
               
                 eperisone 
                 Halcinonide 
                 5-fluorouridine 
               
               
                 Erythromycin 
                 Chlorzoxazone 
                 Cinnarizine 
               
               
                 Mycotoxins 
                 Tretinoin 
                 Azaguanine 
               
               
                 Clioquinol 
                 acemetacin 
                 artemisinine 
               
               
                 geraniol 
                 Carbamazepine 
                 Am 580 
               
               
                 ONO 2235 
                 Tinidazole 
                 Isosorbide 
               
               
                 Praziquantel 
                 nateglinide 
                 Niacinamide 
               
               
                 GW 3965 
                 SU 5416 
                 Dipyridamole 
               
               
                 trimethylcolchicinic acid 
                 3,3,4,5-tetrachlorosalicylanilide 
                 Staurosporine 
               
               
                 Danazol 
                 Stavudine 
                 Pyrazinamide 
               
               
                 Tropicamide 
                 Curcumin 
                 Raloxifene 
               
               
                 4-acetylaminofluorene 
                 Pentolinium Tartrate 
                 Colchicine 
               
               
                 Dipyrone 
                 zileuton 
                 ipriflavone 
               
               
                 Methyltestosterone 
                 salicylamide 
                 Thioridazine 
               
               
                 Warfarin 
                 diphenidol 
                 Metoclopramide 
               
               
                 1-Methyl-3-isobutylxanthine 
                 Hemin 
                 Atractyloside 
               
               
                 nabumetone 
                 9-(2-hydroxy-3-nonyl)adenine 
                 Apomorphine 
               
               
                 Monensin 
                 Nisoldipine 
                 Buthionine Sulfoximine 
               
               
                 cetraxate 
                 4,5-dianilinophthalimide 
                 Prochlorperazine 
               
               
                 Hydralazine 
                 Oxyquinoline 
                 Loperamide 
               
               
                 Propylthiouracil 
                 N-acetylsphingosine 
                 daboiatoxin 
               
               
                 anisindione 
                 ponasterone A 
                 Citric Acid 
               
               
                 Alprazolam 
                 Estriol 
                 pantoprazole 
               
               
                 Phytohemagglutinins 
                 diisopropyl methylphosphonate 
                 Isocarboxazid 
               
               
                 Clomipramine 
                 dibenzazepine 
                 Ticrynafen 
               
               
                 norethindrone acetate 
                 Granisetron 
                 Lithium Carbonate 
               
               
                 Sulfaphenazole 
                 cyclazosin 
                 Triacetin 
               
               
                 Amoxapine 
                 3-nitropropionic acid 
                 Mestranol 
               
               
                 Ofloxacin 
                 Bupropion 
                 hydrazine 
               
               
                 Penicillin G 
                 Ifosfamide 
                 Floxuridine 
               
               
                 Tranexamic Acid 
                 Bendroflumethiazide 
                 idebenone 
               
               
                 Mianserin 
                 flavanone 
                 Malathion 
               
               
                 Neomycin 
                 Aminosalicylic Acid 
                 tosufloxacin 
               
               
                 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4- 
                 Cyproterone Acetate 
                 Ciprofloxacin 
               
               
                 pyridyl)imidazole 
                   
                   
               
               
                 benoxaprofen 
                 dexchlorpheniramine 
                 Fludrocortisone 
               
               
                 Methapyrilene 
                 Guaifenesin 
                 Flurandrenolone 
               
               
                 Fluocinonide 
                 trichlorofluoromethane 
                 Terazosin 
               
               
                 Histamine 
                 6-methoxy-2-naphthylacetic acid 
                 Concanavalin A 
               
               
                 Metformin 
                 Ticlopidine 
                 amitraz 
               
               
                 Primidone 
                 Idarubicin 
                 lansoprazole 
               
               
                 epigallocatechin gallate 
                 desloratadine 
                 Lasalocid 
               
               
                 Flavoxate 
                 doxifluridine 
                 zopiclone 
               
               
                 Sertraline 
                 Clonazepam 
                 Dimenhydrinate 
               
               
                 Cyclosporine 
                 Tacrolimus 
                 Clotrimazole 
               
               
                 Sulfisoxazole 
                 bisphenol A 
                 Cytochalasin D 
               
               
                 mycophenolate mofetil 
                 Albuterol 
                 lactacystin 
               
               
                 Triamterene 
                 Nitrazepam 
                 Glycine 
               
               
                 Carboplatin 
                 Vincamine 
                 Omeprazole 
               
               
                 Gossypol 
                 Amlodipine 
                 Nitrofurazone 
               
               
                 8-Bromo Cyclic Adenosine Monophosphate 
                 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin- 
                 romidepsin 
               
               
                   
                 2-yl-1H-imidazol-2-yl)benzamide 
                   
               
               
                 Hexachlorophene 
                 oxfendazole 
                 gabapentin 
               
               
                 Insulin 
                 Promazine 
                 Dinitrofluorobenzene 
               
               
                 resveratrol 
                 Acetazolamide 
                 quetiapine 
               
               
                 beta-1,3-glucan 
                 Metribolone 
                 Neostigmine 
               
               
                 Merbromin 
                 neuropeptide Y (18-36) 
                 Chlorthalidone 
               
               
                 Paraquat 
                 Methimazole 
                 Epinephrine 
               
               
                 methyl salicylate 
                 flunisolide 
                 Bezafibrate 
               
               
                 doxofylline 
                 Aspirin 
                 glimepiride 
               
               
                 2-Acetylaminofluorene 
                 1,1,1-trichloroethane 
                 2-(4-morpholinoanilino)-6- 
               
               
                   
                   
                 cyclohexylaminopurine 
               
               
                 Milrinone 
                 Ganciclovir 
                 Gemfibrozil 
               
               
                 Phenylephrine 
                 phorbolol myristate acetate 
                 Glipizide 
               
               
                 Mefenamic Acid 
                 Chlormezanone 
                 leflunomide 
               
               
                 Oxymetholone 
                 abamectin 
                 Metronidazole 
               
               
                 Chlordiazepoxide 
                 terbinafine 
                 Triiodothyronine 
               
               
                 Tamoxifen 
                 1-hydroxycholecalciferol 
                 Immunotoxins 
               
               
                 rabeprazole 
                 Cadmium 
                 cyanoginosin LR 
               
               
                 Minoxidil 
                 oxaliplatin 
                 Budesonide 
               
               
                 Fluoxetine 
                 Safrole 
                 lamotrigine 
               
               
                 Nafcillin 
                 Endotoxins 
                 Epirubicin 
               
               
                 Sotalol 
                 Terfenadine 
                 sodium arsenite 
               
               
                 Trifluoperazine 
                 Benzo(a)pyrene 
                 MK 0591 
               
               
                 diflorasone diacetate 
                 Diethylhexyl Phthalate 
                 Oxymetazoline 
               
               
                 Ritonavir 
                 decitabine 
                 Griseofulvin 
               
               
                 clopidogrel 
                 Bretylium Tosylate 
                 6-Mercaptopurine 
               
               
                 loxoprofen 
                 Etidronic Acid 
                 Aflatoxins 
               
               
                 CD 437 
                 4-dichlorobenzene 
                 Rifabutin 
               
               
                 Nafenopin 
                 vanoxerine 
                 4,4′-diaminodiphenylmethane 
               
               
                 Bleomycin 
                 Daunorubicin 
                 Phenobarbital 
               
               
                 4-nonylphenol 
                 Carbimazole 
                 olmesartan 
               
               
                 flubendazole 
                 Losartan 
                 sildenafil 
               
               
                 salsolidine 
                 blebbistatin 
                 Methotrimeprazine 
               
               
                 Calcitriol 
                 ibufenac 
                 Rolipram 
               
               
                 iturelix 
                 Folic Acid 
                 Loratadine 
               
               
                 Tiapamil Hydrochloride 
                 candesartan 
                 Desipramine 
               
               
                 Norepinephrine 
                 bromobenzene 
                 Cholecalciferol 
               
               
                 parbendazole 
                 Ethionamide 
                 venlafaxine 
               
               
                 8-((4-chlorophenyl)thio)cyclic-3′,5-AMP 
                 Tolazoline 
                 bromperidol 
               
               
                 Cefoxitin 
                 Aflatoxin B1 
                 Timolol 
               
               
                 Anisomycin 
                 Labetalol 
                 Phalloidine 
               
               
                 Ethacrynic Acid 
                 trovafloxacin 
                 Amantadine 
               
               
                 Bromisovalum 
                 bephenium hydroxynaphthoate 
                 Protriptyline 
               
               
                 Camptothecin 
                 valdecoxib 
                 Doxapram 
               
               
                 Clemastine 
                 Doxepin 
                 Diethylnitrosamine 
               
               
                 Procarbazine 
                 tranilast 
                 Gallamine Triethiodide 
               
               
                 sulconazole 
                 letrozole 
                 diloxanide furoate 
               
               
                 Phosphorylcholine 
                 Phenacetin 
                 marimastat 
               
               
                 Clenbuterol 
                 Lorazepam 
                 Sulfachlorpyridazine 
               
               
                 fomepizole 
                 Amanitins 
                 Streptozocin 
               
               
                 Aminoglutethimide 
                 Escin 
                 Cromolyn Sodium 
               
               
                 phenethyl isothiocyanate 
                 Ketoprofen 
                 Cefoperazone 
               
               
                 Thioacetamide 
                 Cobalt 
                 trilinolein 
               
               
                 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine 
                 Penicillamine 
                 lapatinib 
               
               
                 Isoniazid 
                 rofecoxib 
                 Quinacrine 
               
               
                 bafilomycin A 
                 Clonidine 
                 Trihexyphenidyl 
               
               
                 4′-N-benzoylstaurosporine 
                 Tetracycline 
                 Triazolam 
               
               
                 Quercetin 
                 Flunarizine 
                 Clozapine 
               
               
                 Betazole 
                 Fluspirilene 
                 Sulpiride 
               
               
                 Nordihydroguaiaretic Acid 
                 oltipraz 
                 celecoxib 
               
               
                 Cyclophosphamide 
                 Clofibric Acid 
                 SB 203580 
               
               
                 Atenolol 
                 Diazepam 
                 Catechin 
               
               
                 benzamil 
                 Dihydroergotamine 
                 Perhexiline 
               
               
                 Propranolol 
                 cephaelin 
                 Y 27632 
               
               
                 Alprostadil 
                 Deoxyglucose 
                 Nizatidine 
               
               
                 Cycloserine 
                 Alprenolol 
                 Metaproterenol 
               
               
                 Captopril 
                 Vincristine 
                 wortmannin 
               
               
                 Nortriptyline 
                 imatinib 
                 Clarithromycin 
               
               
                 Choline 
                 Famotidine 
                 Rotenone 
               
               
                 Carbachol 
                 Vidarabine 
                 Nocodazole 
               
               
                 Phenelzine 
                 Moxisylyte 
                 gemcitabine 
               
               
                 Paroxetine 
                 Cocaine 
                 Verapamil 
               
               
                 Ionomyin 
                 Deferoxamine 
                 Haloperidol 
               
               
                 olanzapine 
                 Ramipril 
                 Levodopa 
               
               
                 Melatonin 
                 Emetine 
                 Podophyllotoxin 
               
               
                 Maprotiline 
                 Azacitidine 
                 Amitriptyline 
               
               
                 Nitric Oxide 
                 Thapsigargin 
                 Nevirapine 
               
               
                 U 0126 
                 Dichlorvos 
                 Allopurinol 
               
               
                 Ascorbic Acid 
                 triptolide 
                 Atropine 
               
               
                 Perphenazine 
                 ochratoxin A 
                 Ribavirin 
               
               
                 Vitamin K 3 
                 Kainic Acid 
                 Gentamicins 
               
               
                 Chitosan 
                   
                   
               
            
           
           
               
            
               
                 V2. Molecules that downregulate PPAR-y: 
               
            
           
           
               
               
               
            
               
                 troglitazone 
                 pioglitazone 
                 tomatidine 
               
               
                 ebastine 
                 N-Methylaspartate 
                 Diphenhydramine 
               
               
                 nifuroxazide 
                 Betaxolol 
                 imazalil 
               
               
                 Prostaglandins E 
                 titanium dioxide 
                 Benzethonium 
               
               
                 chloroxylenol 
                 Mycophenolic Acid 
                 Hydrogel 
               
               
                 oxiconazole 
                 8-(3-Chlorostyryl)-1,3,7- 
                 15-deoxy-delta(12,14)- 
               
               
                   
                 trimethylxanthine 
                 prostaglandin J2 
               
               
                 Thiostrepton 
                 Methylcholanthrene 
                 Dinoprostone 
               
               
                 Ibuprofen 
                 lycorine 
                 Gentian Violet 
               
               
                 1,2,3-trichloropropane 
                 Itraconazole 
                 Isoproterenol 
               
               
                 Etodolac 
                 Ketoconazole 
                 Acetylmuramyl-Alanyl- 
               
               
                   
                   
                 Isoglutamine 
               
               
                 Sulindac 
                 Zidovudine 
                 Hydrocortisone 
               
               
                 pramoxine 
                 Vinblastine 
                 telmisartan 
               
               
                 Estradiol 
                 Fenoprofen 
                 Adenosine-5′-(N- 
               
               
                   
                   
                 ethylcarboxamide) 
               
               
                 Phenoxybenzamine 
                 Isotretinoin 
                 Fluocinolone Acetonide 
               
               
                 Droperidol 
                 atorvastatin 
                 Foscarnet 
               
               
                 Topotecan 
                 arsenic trioxide 
                 MRK 003 
               
               
                 Hemicholinium 3 
                 Ethylnitrosourea 
                 Immunoglobulins, Intravenous 
               
               
                 Acetaminophen 
                 Valproic Acid 
                 Methylnitrosourea 
               
               
                 BCG Vaccine 
                 carvedilol 
                 Primaquine 
               
               
                 Chlorhexidine 
                 Chlorambucil 
                 Ketorolac 
               
               
                 gliquidone 
                 Ceftazidime 
                 ranolazine 
               
               
                 Apazone 
                 withaferin A 
                 Dexamethasone 
               
               
                 Finasteride 
                 Thioguanine 
                 Methyldopa 
               
               
                 Cholera Toxin 
                 Coumarins 
                 4-hydroxytamoxifen 
               
               
                 Ethylene Glycol 
                 Antigen-Antibody Complex 
                 zardaverine 
               
               
                 Nitrendipine 
                 Methotrexate 
                 Chorionic Gonadotropin 
               
               
                 Dichlororibofuranosylbenzimidazole 
                 Cetylpyridinium 
                 Growth Hormone 
               
               
                 Nystatin 
                 Cortisone 
                 Indomethacin 
               
               
                 Carbon Tetrachloride 
                 Chlorpromazine 
                 Methoxsalen 
               
               
                 fazarabine 
                 Ambroxol 
                 Busulfan 
               
               
                 Fluconazole 
                 Cytarabine 
                 Digoxin 
               
               
                 infliximab 
                 lornoxicam 
                 Diclofenac 
               
               
                 cinchonine 
                 Enoxacin 
                 Naproxen 
               
               
                 Monocrotaline 
                 monobenzone 
                 Remoxipride 
               
               
                 Lovastatin 
                 nimesulide 
                 Cefuroxime 
               
               
                 Ultraviolet Rays 
                 Dobutamine 
                 4-octylphenol 
               
               
                 riddelliine 
                 fluvastatin 
                 Pyrilamine 
               
               
                 indole-3-carbinol 
                 Dinoprost 
                 monophosphoryl lipid A 
               
               
                 sapphyrin 
                 Roflumilast 
                 Albendazole 
               
               
                 Baclofen 
                 Norethindrone 
                 benazepril 
               
               
                 phenothiazine 
                 irbesartan 
                 Azithromycin 
               
               
                 cerivastatin 
                 phosphonoacetamide 
                 Disulfiram 
               
               
                 Tocainide 
                 marinobufagenin 
                 Vanadates 
               
               
                 Tetrachlorodibenzodioxin 
                 Dexfenfluramine 
                 Betamethasone 
               
               
                 tenidap 
                 sparfloxacin 
                 Poly I-C 
               
               
                 4-(N-methyl-N-nitrosamino)-1-(3-  
                 Mebendazole 
                 3,3′,5-triiodothyroacetic acid 
               
               
                 pyridyl)-1-butanone 
                   
                   
               
               
                 Debrisoquin 
                 Strophanthidin 
                 senecionine 
               
               
                 Ethinyl Estradiol 
                 lanatoside C 
                 Ethoxyquin 
               
               
                 Fluphenazine 
                 meloxicam 
                 Hydroxyurea 
               
               
                 shikonin 
                 Diflunisal 
                 alginic acid 
               
               
                 Glafenine 
                 Zalcitabine 
                 Palmitic Acid 
               
               
                 Prednisone 
                 Simvastatin 
                 2-(1H-indazol-4-yl)-6-(4- 
               
               
                   
                   
                 methanesulfonylpiperazin- 
               
               
                   
                   
                 1-ylmethyl)-4-morpholin-4- 
               
               
                   
                   
                 ylthieno(3,2-d)pyrimidine 
               
               
                 sunitinib 
                 erlotinib 
                 Azathioprine 
               
               
                 Fenoterol 
                 Mifepristone 
                 geldanamycin 
               
               
                 Hyaluronic Acid 
                 Gonadotropins 
                 Trimetazidine 
               
               
                 Cimetidine 
                 Tetrahydrocannabinol 
                 Pravastatin 
               
               
                 1,10-phenanthroline 
                 trichostatin A 
                 lomefloxacin 
               
               
                 beta-Naphthoflavone 
                 Econazole 
                 Estrogens 
               
               
                 piperlonguminine 
                 Ergocalciferols 
                 tracazolate 
               
               
                 Doxorubicin 
                 Bisacodyl 
                 Lamivudine 
               
               
                 glycidol 
                 Forskolin 
                 acidocin CH5,  Lactobacillus   
               
               
                   
                   
                 
                   acidophilus 
                 
               
               
                 NSC 652287 
                 Cisplatin 
                 pepstatin 
               
               
                 Spiperone 
                 Tryptophan 
                 Kanamycin 
               
               
                 vorinostat 
                 valsartan 
                 Lithium 
               
               
                 hydroquinone 
                 Streptomycin 
                 17-(allylamino)-17- 
               
               
                   
                   
                 demethoxygeldanamycin 
               
               
                 sodium selenate 
                 Amiodarone 
                 Dicumarol 
               
               
                 Carmustine 
                 Metoprolol 
                 acadesine 
               
               
                 Genistein 
                 gefitinib 
                 Tubocurarine 
               
               
                 Papaverine 
                 Methyl Methanesulfonate 
                 Physostigmine 
               
               
                 Clofibrate 
                 Doxazosin 
                 Risperidone 
               
               
                 Ranitidine 
                 apicidin 
                 Citalopram 
               
               
                 fasudil 
                 4-methyl-N-(3-(4-methylimidazol-1-yl)- 
                 Betahistine 
               
               
                   
                 5-(trifluoromethyl)phenyl)-3-((4-pyridin-3- 
                   
               
               
                   
                 ylpyrimidin-2-yl)amino)benzamide 
                   
               
               
                 ellipticine 
                 Miconazole 
                 Digitoxin 
               
               
                 Diltiazem 
                 Thiethylperazine 
                 Chlorpyrifos 
               
               
                 Furazolidone 
                 LBH589 
                 diphenylpyraline 
               
               
                 dasatinib 
                 Dactinomycin 
                 Puromycin 
               
               
                 Furosemide 
                 Promethazine 
                 Lomustine 
               
               
                 hesperetin 
                 Mitomycin 
                 Pyrogallol 
               
               
                 Altretamine 
                 linezolid 
                 N-Methyl-3,4- 
               
               
                   
                   
                 methylenedioxyamphetamine 
               
               
                 Tranylcypromine 
                 Vitamin E 
                 monorden 
               
               
                 Ouabain 
                 Paclitaxel 
                 Caffeine 
               
               
                 isoascorbic acid 
                 ciprofibrate 
                 Netilmicin 
               
               
                 Azauridine 
                 Nimodipine 
                 pirinixic acid 
               
               
                 Chloramphenicol 
                 lysophosphatidic acid 
                 Enalapril 
               
               
                 mono-(2-ethylhexyl)phthalate 
                 Dicyclomine 
                 Cycloheximide 
               
               
                 Imipramine 
                 Buspirone 
                 Alpha-Amanitin 
               
               
                 Theophylline 
                 Probucol 
                 pralidoxime 
               
               
                 Fluorouracil 
                 irinotecan 
                 sorafenib 
               
               
                 bortezomib 
                   
                   
               
            
           
           
               
            
               
                 W1. Molecules that upregulate TMEM27: 
               
            
           
           
               
               
               
            
               
                 Mitomycin 
                 resveratrol 
                 cidofovir 
               
               
                 NG-Nitroarginine Methyl Ester 
                 Neomycin 
                 Neostigmine 
               
               
                 Lorazepam 
                 flubendazole 
                 Methocarbamol 
               
               
                 Methylnitrosourea 
                 hydrazine 
                 Fenbendazole 
               
               
                 fluvastatin 
                 Cetylpyridinium 
                 geraniol 
               
               
                 PK 11195 
                 Promazine 
                 Cymarine 
               
               
                 Oxytetracycline 
                 PI103 
                 testosterone 17 beta-cypionate 
               
               
                 atorvastatin 
                 Mycophenolic Acid 
                 Famotidine 
               
               
                 norethindrone acetate 
                 salicylamide 
                 diphenidol 
               
               
                 Nitrendipine 
                 Enterobactin 
                 Clomipramine 
               
               
                 Poly I-C 
                 Doxorubicin 
                 closantel 
               
               
                 artemisinine 
                 ipriflavone 
                 Bromisovalum 
               
               
                 nateglinide 
                 Daunorubicin 
                 Clotrimazole 
               
               
                 Alprazolam 
                 Verapamil 
                 oxcarbazepine 
               
               
                 pralidoxime 
                 Galantamine 
                 balsalazide 
               
               
                 Nizatidine 
                 sulfathiazole 
                 Diazepam 
               
               
                 benazepril 
                 Moclobemide 
                 3-hydroxyacetanilide 
               
               
                 Testosterone 
                 Labetalol 
                 Flunarizine 
               
               
                 Baclofen 
                 Ethinyl Estradiol 
                 Tramadol 
               
               
                 Cisplatin 
                 Piracetam 
                 4,4′-diaminodiphenylmethane 
               
               
                 Tranexamic Acid 
                 Diethylstilbestrol 
                 Aflatoxin B1 
               
               
                 gabapentin 
                 Methimazole 
                 Benzo(a)pyrene 
               
               
                 Hemin 
                 Paroxetine 
                 Clofibrate 
               
               
                 olanzapine 
                 oxybutynin 
                 Zinc Oxide 
               
               
                 6-Mercaptopurine 
                 Aclarubicin 
                 Pentoxifylline 
               
               
                 Finasteride 
                 Clofibric Acid 
                 2-(1H-indazol-4-yl)-6-(4- 
               
               
                   
                   
                 methanesulfonylpiperazin- 
               
               
                   
                   
                 1-ylmethyl)-4-morpholin-4- 
               
               
                   
                   
                 ylthieno(3,2-d)pyrimidine 
               
               
                 Prazosin 
                 Stanozolol 
                 Cimetidine 
               
               
                 Busulfan 
                 nimesulide 
                 Simvastatin 
               
               
                 Metoprolol 
                 Secobarbital 
                 Benzalkonium Compounds 
               
               
                 Tamoxifen 
                 Mifepristone 
                 Amlodipine 
               
               
                 Sulindac 
                 anastrozole 
                 Sotalol 
               
               
                 Propranolol 
                 Chloroform 
                 Clemastine 
               
               
                 Clarithromycin 
                 Amitriptyline 
                 quetiapine 
               
               
                 geldanamycin 
                 Prednisolone 
                 Thiabendazole 
               
               
                 moxonidine 
                 cerivastatin 
                 valsartan 
               
               
                 Captopril 
                 Alpha-Amanitin 
                 Procaine 
               
               
                 Spironolactone 
                 motexafin gadolinium 
                 Itraconazole 
               
               
                 Miconazole 
                 Econazole 
                 Cytokines 
               
               
                 leflunomide 
                 Dimethyl Sulfoxide 
                 erlotinib 
               
               
                 Calcium 
                 Acetaminophen 
                 Hydroxyurea 
               
               
                 Etoposide 
                 Ethylene Glycol 
                 Bezafibrate 
               
               
                 Clobetasol 
                 Indomethacin 
                 Diethylhexyl Phthalate 
               
               
                 Clonidine 
                 Methotrexate 
                 Enterotoxins 
               
               
                 2-amino-1-methyl-6- 
                 Mercuric Chloride 
                 Glycine 
               
               
                 phenylimidazo(4,5-b)pyridine 
                   
                   
               
               
                 Ketoconazole 
                 Sumatriptan 
                 Aspirin 
               
               
                 Pemoline 
                 Chlorambucil 
                 Fenoprofen 
               
               
                 Equilin 
                 Cyproheptadine 
                 dibenzazepine 
               
               
                 Lovastatin 
                 Griseofulvin 
                 Diclofenac 
               
               
                 Cyclosporine 
                 decitabine 
                 Zinc 
               
               
                 zomepirac 
                 Carmustine 
                 aceclofenac 
               
               
                 Chlormadinone Acetate 
                 Ibuprofen 
                 Aminocaproic Acids 
               
               
                 meloxicam 
                 Fluphenazine 
                 Ergocalciferols 
               
               
                 Clomiphene 
                 ochratoxin A 
                 dexibuprofen 
               
               
                 Roxarsone 
                 Chloramphenicol 
                 Norethindrone 
               
               
                 Ribavirin 
                 withaferin A 
                 Diflunisal 
               
               
                 Ritonavir 
                 Azacitidine 
                 Sulfadimethoxine 
               
               
                 enrofloxacin 
                 Fenofibrate 
                 monastrol 
               
               
                 trichostatin A 
                 vinylidene chloride 
                 blebbistatin 
               
               
                 Doxycycline 
                 Vincristine 
                 Naproxen 
               
               
                 Dantrolene 
                 Ethanol 
                 Ramipril 
               
               
                 Piroxicam 
                 Carbamazepine 
                 Tretinoin 
               
               
                 Bromhexine 
                 17-(allylamino)-17- 
                 fulvestrant 
               
               
                   
                 demethoxygeldanamycin 
                   
               
               
                 Gemfibrozil 
                 Carboplatin 
                 Hydrochloric Acid 
               
               
                 candesartan 
                 Soman 
                 Dinoprost 
               
               
                 Cycloheximide 
                 Netilmicin 
                 Folic Acid 
               
               
                 HI 6 
                 Sirolimus 
                 Dimethylformamide 
               
               
                 zileuton 
                 Hydrochlorothiazide 
                 bevacizumab 
               
               
                 methylatropine 
                 Tetracycline 
                 pantoprazole 
               
               
                 lapatinib 
                 Quercetin 
                 Thapsigargin 
               
               
                 rofecoxib 
                 Carbon Tetrachloride 
                 oxaliplatin 
               
               
                 Rotenone 
                 valdecoxib 
                 Azathioprine 
               
               
                 Nicotine 
                 Tacrine 
                 Lactic Acid 
               
               
                 Epirubicin 
                 vorinostat 
                 bortezomib 
               
               
                 quelamycin 
                 Fluconazole 
                 Penicillamine 
               
               
                 U 0126 
                 Progesterone 
                 infliximab 
               
               
                 Acetazolamide 
                 Isotretinoin 
                 Risperidone 
               
               
                 Chlorpromazine 
                 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl- 
                 X-Rays 
               
               
                   
                 1H-imidazol-2-yl)benzamide 
                   
               
               
                 Bleomycin 
                   
                   
               
            
           
           
               
            
               
                 W2. Molecules that downregulate TMEM27: 
               
            
           
           
               
               
               
            
               
                 oxfendazole 
                 Oxyquinoline 
                 Estriol 
               
               
                 meropenem 
                 chloroxylenol 
                 Cyproterone Acetate 
               
               
                 sorafenib 
                 cyclonite 
                 Nystatin 
               
               
                 Trichloroacetic Acid 
                 Aztreonam 
                 pramoxine 
               
               
                 Atropine 
                 daidzein 
                 Gentamicins 
               
               
                 Menthol 
                 Am 580 
                 bromodichloromethane 
               
               
                 Melphalan 
                 Fonofos 
                 Promegestone 
               
               
                 bisphenol A 
                 Acyclovir 
                 Bacitracin 
               
               
                 sulconazole 
                 Noscapine 
                 Estradiol 
               
               
                 Allopurinol 
                 gefitinib 
                 Lead 
               
               
                 VX 
                 Acetylmuramyl-Alanyl-Isoglutamine 
                 chlorinated dibenzofurans 
               
               
                 Valproic Acid 
                 famciclovir 
                 Fluocinolone Acetonide 
               
               
                 lead acetate 
                 4′-N-benzoylstaurosporine 
                 2-dichlorobenzene 
               
               
                 Genistein 
                 Diethylnitrosamine 
                 Aphidicolin 
               
               
                 hydroquinone 
                 beta-cyclodextrin-benzaldehyde 
                 sodium arsenite 
               
               
                 SU 5402 
                 shikonin 
                 Paclitaxel 
               
               
                 Cephaloridine 
                 tianeptine 
                 compactin 
               
               
                 CPG-oligonucleotide 
                 1,2,3-trichloropropane 
                 3-deazaneplanocin 
               
               
                 fragment C, human serum albumin 
                 Pravastatin 
                 Theophylline 
               
               
                 Ifosfamide 
                 Acetylcysteine 
                 enzastaurin 
               
               
                 linalool 
                 Thioguanine 
                 triadimefon 
               
               
                 gatifloxacin 
                 oxaprozin 
                 penciclovir 
               
               
                 Dexamethasone 
                 Ouabain 
                 Perhexiline 
               
               
                 Chorionic Gonadotropin 
                 Vancomycin 
                 lead tetraacetate 
               
               
                 Metribolone 
                 Trichloroethylene 
                 trovafloxacin 
               
               
                 Benzethonium 
                 pioglitazone 
                 Insulin 
               
               
                 4-nonylphenol 
                 Flurbiprofen 
                 Colchicine 
               
               
                 Fluoxetine 
                 Cam ptothecin 
                 Cadmium 
               
               
                 Cyclophosphamide 
                 sulforafan 
                 Monocrotaline 
               
               
                 Papaverine 
                 Danazol 
                 Luteinizing Hormone 
               
               
                 Trimethadione 
                 Omeprazole 
                 Fluorouracil 
               
               
                 Medroxyprogesterone Acetate 
                 Isoniazid 
                 Disopyramide 
               
               
                 aristolochic acid I 
                 Ultraviolet Rays 
                 Dihydrotestosterone 
               
               
                 Flutamide 
                 Methylprednisolone 
                 rosiglitazone 
               
               
                 Triiodothyronine 
                 Bithionol 
                 Caffeine 
               
               
                 Amiodarone 
                 Rifampin 
                 Phenacetin 
               
               
                 Tetradecanoylphorbol Acetate 
                 Phenobarbital 
                 Tetrachlorodibenzodioxin 
               
            
           
           
               
            
               
                 X1. Molecules that upregulate ACE2: 
               
            
           
           
               
               
               
            
               
                 Oxytetracycline 
                 Ethylene Dibromide 
                 erlotinib 
               
               
                 Calcium 
                 diperodon 
                 N-methylolacrylamide 
               
               
                 Y 27632 
                 Fursultiamin 
                 hydroxyachillin 
               
               
                 Sulfisoxazole 
                 Bendroflumethiazide 
                 Terbutaline 
               
               
                 Aflatoxins 
                 Trichlormethiazide 
                 quintozene 
               
               
                 althiazide 
                 naphthalan 
                 Pyrogens 
               
               
                 Poly I-C 
                 acetylleucine 
                 epitiostanol 
               
               
                 2-(4-morpholinoanilino)-6- 
                 Cytarabine 
                 Colistin 
               
               
                 cyclohexylaminopurine 
                   
                   
               
               
                 2-dichlorobenzene 
                 Cytochalasin D 
                 cidofovir 
               
               
                 Trichloroepoxypropane 
                 Pregnenolone 
                 Demeclocycline 
               
               
                 apratoxin A 
                 Sulfamethazine 
                 Humic Substances 
               
               
                 Piperacillin 
                 4-dichlorobenzene 
                 Dequalinium 
               
               
                 Cefmetazole 
                 ethaverine 
                 SC 514 
               
               
                 fosfosal 
                 vinpocetine 
                 carbetapentane 
               
               
                 Ozone 
                 canadine 
                 diphemanil methylsulfate 
               
               
                 1,2-dilinolenoyl-3-(4-aminobutyryl)propane- 
                 Doxorubicin 
                 Reserpine 
               
               
                 1,2,3-triol 
                   
                   
               
               
                 4-hydroxy-2-nonenal 
                 Cinoxacin 
                 cinchonine 
               
               
                 Testosterone 
                 Methylene Chloride 
                 bromobenzene 
               
               
                 Captopril 
                 N-nitrosomorpholine 
                 tyloxapol 
               
               
                 Ethambutol 
                 oxybutynin 
                 Ipratropium 
               
               
                 sertaconazole 
                 Isoflurane 
                 Tetradecanoylphorbol Acetate 
               
               
                 Tranylcypromine 
                 Monocrotaline 
                 solasodine 
               
               
                 Oxytocin 
                 Cefotaxime 
                 citiolone 
               
               
                 flunisolide 
                 Tamoxifen 
                 Propidium 
               
               
                 Amrinone 
                 Ethanol 
                 gefitinib 
               
               
                 Biotin 
                 Daunorubicin 
                 Sulfamethoxypyridazine 
               
               
                 Thioacetamide 
                 Gossypol 
                 monobenzone 
               
               
                 carcinine 
                 Ribavirin 
                 Roxithromycin 
               
               
                 bevacizumab 
                 Phentolamine 
                 Lobeline 
               
               
                 Bromocriptine 
                 wortmannin 
                 Flunarizine 
               
               
                 vorinostat 
                 medrysone 
                 16-ketoestradiol 
               
               
                 Ampicillin 
                 Dextran Sulfate 
                 dexibuprofen 
               
               
                 Clobetasol 
                 Mitomycin 
                 Alpha-Amanitin 
               
               
                 Tretinoin 
                 Sulfamethoxazole 
                 Paroxetine 
               
               
                 aluminum sulfate 
                 oxidized-L-alpha-1-palmitoyl-2- 
                 Dehydroepiandrosterone 
               
               
                   
                 arachidonoyl-sn-glycero-3- 
                   
               
               
                   
                 phosphorylcholine 
                   
               
               
                 vinclozolin 
                 triptolide 
                 decitabine 
               
               
                 Dexamethasone 
                 peginterferon alfa-2a 
                 Epitestosterone 
               
               
                 4-hydroxytamoxifen 
                 Nitrofurantoin 
                 Cholecalciferol 
               
               
                 blebbistatin 
                 trichostatin A 
                 Azacitidine 
               
               
                 Diquat 
                 Procainamide 
                 Forskolin 
               
               
                 Cyclophosphamide 
                 1-Methyl-4-phenyl-1,2,3,6- 
                 torsemide 
               
               
                   
                 tetrahydropyridine 
                   
               
               
                 mycophenolate mofetil 
                 Hydroxyzine 
                 Aflatoxin B1 
               
               
                 Mycophenolic Acid 
                 Oxyquinoline 
                 Hydralazine 
               
               
                 LBH589 
                 Hemin 
                 pralidoxime 
               
               
                 Mebendazole 
                 Cephalothin 
                 celecoxib 
               
               
                 Hydrochloric Acid 
                 fulvestrant 
                 docetaxel 
               
               
                 pioglitazone 
                 Enalapril 
                 Chitosan 
               
               
                 Rifampin 
                 Carbamazepine 
                 Dactinomycin 
               
               
                 Genistein 
                 Diazepam 
                 Nifedipine 
               
               
                 Cycloheximide 
                 Lactic Acid 
                 Diethylhexyl Phthalate 
               
               
                 Bezafibrate 
                 Atropine 
                 Promethazine 
               
               
                 Metformin 
                 Formaldehyde 
                 Isoproterenol 
               
               
                 Asbestos 
                   
                   
               
            
           
           
               
            
               
                 X2. Molecules that downregulate ACE2: 
               
            
           
           
               
               
               
            
               
                 sunitinib 
                 polidocanol 
                 VX 
               
               
                 sorafenib 
                 ubiquinol 
                 Dichlorvos 
               
               
                 naphthalene 
                 2-methoxyestradiol 
                 Azoxymethane 
               
               
                 Ganciclovir 
                 shikonin 
                 1,5-naphthalenediamine 
               
               
                 6-bromoindirubin-3′-oxime 
                 1-amino-2,4-dibromoanthraquinone 
                 Tacrolimus 
               
               
                 Benzalkonium Compounds 
                 Hydrogel 
                 Niacinamide 
               
               
                 Bleomycin 
                 ferric nitrilotriacetate 
                 Malathion 
               
               
                 Shiga Toxin 
                 Folic Acid 
                 tris(2,3-dibromopropyl)phosphate 
               
               
                 Lead 
                 bromodichloromethane 
                 Clodronic Acid 
               
               
                 Furosemide 
                 heliotrine 
                 Quercetin 
               
               
                 enrofloxacin 
                 perfluorooctane sulfonic acid 
                 Choline 
               
               
                 Norfloxacin 
                 valdecoxib 
                 Lindane 
               
               
                 testosterone 17 beta-cypionate 
                 Allopurinol 
                 DDT 
               
               
                 Tetrachloroethylene 
                 Ultraviolet Rays 
                 Cadmium 
               
               
                 Acrolein 
                 lead tetraacetate 
                 4′-N-benzoylstaurosporine 
               
               
                 Cyclosporine 
                 imatinib 
                 Propylthiouracil 
               
               
                 Sulindac 
                 SB 203580 
                 versipelostatin 
               
               
                 Dihydrotestosterone 
                 Diazinon 
                 Cisplatin 
               
               
                 sulmazole 
                 Methapyrilene 
                 Eugenol 
               
               
                 Terfenadine 
                 Enterotoxins 
                 Diethylstilbestrol 
               
               
                 Fluocinolone Acetonide 
                 R 848 
                 Methimazole 
               
               
                 enterotoxin B, 
                 Theophylline 
                 Netilmicin 
               
               
                 staphylococcal 
                   
                   
               
               
                 aristolochic acid I 
                 cyclonite 
                 Flurbiprofen 
               
               
                 chlorinated dibenzofurans 
                 SU 5402 
                 infliximab 
               
               
                 Estradiol 
                 Tacrine 
                 oxaprozin 
               
               
                 Bromisovalum 
                 Ethylnitrosourea 
                 Papaverine 
               
               
                 Tetrachlorodibenzodioxin 
                 Dinitrofluorobenzene 
                 Deoxyglucose 
               
               
                 Prednisolone 
                 Capsaicin 
                 Sirolimus 
               
               
                 Praziquantel 
                 Acetaminophen 
                 fluvastatin 
               
               
                 atorvastatin 
                 Phosgene 
                 Fluoxetine 
               
               
                 CPG-oligonucleotide 
                 Bacitracin 
                 4-(4-fluorophenyl)-2-(4- 
               
               
                   
                   
                 hydroxyphenyl)-5-(4- 
               
               
                   
                   
                 pyridyl)imidazole 
               
               
                 Ethionine 
                 Paclitaxel 
                 rosiglitazone 
               
               
                 U 0126 
                 trovafloxacin 
                 Valproic Acid 
               
               
                 Carboplatin 
                 lapatinib 
                 Isotretinoin 
               
               
                 Azathioprine 
                 Epirubicin 
                 Naproxen 
               
               
                 leflunomide 
                 Lovastatin 
                 bicalutamide 
               
               
                 Isoniazid 
                 Particulate Matter 
                 Methotrexate 
               
               
                 17-(allylamino)-17-demethoxygeldanamycin 
                 Colchicine 
                 Vinblastine 
               
               
                 Insulin 
                 X-Rays 
                 2-(4-morpholinyl)-8-phenyl- 
               
               
                   
                   
                 4H-1-benzopyran-4-one 
               
               
                 irinotecan 
                 oxaliplatin 
                 bisphenol A 
               
               
                 arsenic trioxide 
                 Cardiotoxins 
                 Progesterone 
               
               
                 Hydrocortisone 
                 Cortisone 
                 Danazol 
               
               
                 Mifepristone 
                 1-Methyl-3-isobutylxanthine 
                 Risperidone 
               
               
                 Phenobarbital 
                 Trimethadione 
                 Omeprazole 
               
               
                 Ifosfamide 
                 Chlorambucil 
                 Benzo(a)pyrene 
               
               
                 Etoposide 
                 Doxycycline 
                 Diclofenac 
               
               
                 Gemfibrozil 
                 Hydrogen Peroxide 
                   
               
            
           
           
               
            
               
                 Y1. Molecules that upregulate PPAR-a: 
               
            
           
           
               
               
               
            
               
                 Fenofibrate 
                 N-Ac-CHAVC-NH2 
                 ferulic acid 
               
               
                 ibufenac 
                 Teicoplanin 
                 1-hydroxycholecalciferol 
               
               
                 N, N′-diphenyl-4-phenylenediamine 
                 eperisone 
                 tranilast 
               
               
                 temafloxacin 
                 cetraxate 
                 bromfenac 
               
               
                 Ciprofloxacin 
                 Fludrocortisone 
                 sparfloxacin 
               
               
                 Zalcitabine 
                 Sotalol 
                 amitraz 
               
               
                 benoxaprofen 
                 Amlodipine 
                 Dipyrone 
               
               
                 piclamilast 
                 trovafloxacin 
                 1,1,1-trichloroethane 
               
               
                 oxfendazole 
                 Safrole 
                 Acetylcysteine 
               
               
                 Nafenopin 
                 Butyric Acid 
                 Rifabutin 
               
               
                 rabeprazole 
                 Spironolactone 
                 Ketorolac 
               
               
                 sodium arsenite 
                 1-(2-cyano-3,12-dioxooleana-1,9- 
                 methylparaben 
               
               
                   
                 dien-28-oyl)imidazole 
                   
               
               
                 Ethylestrenol 
                 Cinnarizine 
                 methyl salicylate 
               
               
                 Sulindac 
                 Ibuprofen 
                 zomepirac 
               
               
                 Erythromycin Ethylsuccinate 
                 Cefsulodin 
                 ONO 2235 
               
               
                 pantoprazole 
                 Lomustine 
                 Bromisovalum 
               
               
                 Citric Acid 
                 ipriflavone 
                 Melatonin 
               
               
                 phenylhydrazine 
                 anastrozole 
                 Omeprazole 
               
               
                 Busulfan 
                 zileuton 
                 2-Acetylaminofluorene 
               
               
                 Roflumilast 
                 beta-Naphthoflavone 
                 Bupropion 
               
               
                 hydrazine 
                 sulfathiazole 
                 troglitazone 
               
               
                 Ergocalciferols 
                 Sulfaphenazole 
                 bromodichloromethane 
               
               
                 Disulfiram 
                 Azathioprine 
                 geraniol 
               
               
                 rosiglitazone 
                 Carbamazepine 
                 Rolipram 
               
               
                 Cetylpyridinium 
                 Perhexiline 
                 Ethanol 
               
               
                 Tacrine 
                 Stanozolol 
                 Amiodarone 
               
               
                 Fenbendazole 
                 Thioguanine 
                 phenothiazine 
               
               
                 Raloxifene 
                 Erythromycin 
                 Methylcholanthrene 
               
               
                 Diethylnitrosamine 
                 2-nitrofluorene 
                 flubendazole 
               
               
                 bisphenol A 
                 Ticrynafen 
                 Methyldopa 
               
               
                 Digoxin 
                 Auranofin 
                 zopiclone 
               
               
                 sildenafil 
                 balsalazide 
                 Praziquantel 
               
               
                 Diclofenac 
                 Clomipramine 
                 Propanil 
               
               
                 pioglitazone 
                 rofecoxib 
                 Promethazine 
               
               
                 Amantadine 
                 lead acetate 
                 Acetaminophen 
               
               
                 Clofibric Acid 
                 Pravastatin 
                 Epitestosterone 
               
               
                 Norethindrone 
                 harman 
                 Phenacetin 
               
               
                 Nevirapine 
                 Valproic Acid 
                 Foscarnet 
               
               
                 oxcarbazepine 
                 deferiprone 
                 Acetazolamide 
               
               
                 Clonazepam 
                 Neomycin 
                 lead tetraacetate 
               
               
                 imiquimod 
                 Epirubicin 
                 Niacinamide 
               
               
                 Thiabendazole 
                 erlotinib 
                 Tocainide 
               
               
                 zaleplon 
                 6-Mercaptopurine 
                 Lovastatin 
               
               
                 salicylamide 
                 Mefenamic Acid 
                 Ethylene Glycol 
               
               
                 Aminoglutethimide 
                 hexachloroethane 
                 Alprazolam 
               
               
                 Fluphenazine 
                 1,2-dilinolenoyl-3-(4- 
                 Clotrimazole 
               
               
                   
                 aminobutyryl)propane-1,2,3-triol 
                   
               
               
                 Clarithromycin 
                 Indomethacin 
                 Lidocaine 
               
               
                 Methapyrilene 
                 Griseofulvin 
                 torsemide 
               
               
                 Etoposide 
                 4,4′-diaminodiphenylmethane 
                 Bithionol 
               
               
                 nimesulide 
                 Triacetin 
                 Nisoldipine 
               
               
                 Dexamethasone 
                 Ketoconazole 
                 3-hydroxyacetanilide 
               
               
                 terbinafine 
                 Finasteride 
                 Mifepristone 
               
               
                 imatinib 
                 Neostigmine 
                 lamotrigine 
               
               
                 MRK 003 
                 Citalopram 
                 4-biphenylamine 
               
               
                 Oxymetazoline 
                 Bezafibrate 
                 Naproxen 
               
               
                 Ofloxacin 
                 gefitinib 
                 Estradiol 
               
               
                 Nifedipine 
                 Sulfisoxazole 
                 Trichloroethylene 
               
               
                 fipronil 
                 Albendazole 
                 cryptoxanthin 
               
               
                 Dimethylformamide 
                 norethindrone acetate 
                 Carmustine 
               
               
                 Fluconazole 
                 celecoxib 
                 Dicloxacillin 
               
               
                 Pyrogallol 
                 Enoxacin 
                 Bromhexine 
               
               
                 Tolazamide 
                 geldanamycin 
                 Oxytetracycline 
               
               
                 aluminum sulfate 
                 Nitrofurantoin 
                 Itraconazole 
               
               
                 Aclarubicin 
                 gamma-Tocopherol 
                 Minoxidil 
               
               
                 Chloroform 
                 Choline 
                 Caffeine 
               
               
                 4-nonylphenol 
                 Simazine 
                 Acyclovir 
               
               
                 Streptomycin 
                 cornpactin 
                 Moxisylyte 
               
               
                 tenofovir 
                 Pyrazinamide 
                 dexamisole 
               
               
                 irinotecan 
                 Ticlopidine 
                 bicalutamide 
               
               
                 Ivermectin 
                 garcinol 
                 Practolol 
               
               
                 Econazole 
                 Chlorpromazine 
                 ovalicin 
               
               
                 Gemfibrozil 
                 closantel 
                 Simvastatin 
               
               
                 mosapride 
                 Morphine 
                 Sertraline 
               
               
                 tosufloxacin 
                 Gliclazide 
                 Dexfenfluramine 
               
               
                 Indinavir 
                 Fenoprofen 
                 trilinolein 
               
               
                 fluvastatin 
                 Curcumin 
                 vinylidene chloride 
               
               
                 Doxycycline 
                 leflunomide 
                 Menthol 
               
               
                 diisopropyl methylphosphonate 
                 diloxanide furoate 
                 abamectin 
               
               
                 Roxarsone 
                 artemisinine 
                 Staurosporine 
               
               
                 Levamisole 
                 bromobenzene 
                 phenacemide 
               
               
                 crotamiton 
                 Metoclopramide 
                 Propylthiouracil 
               
               
                 Cytarabine 
                 Mannitol 
                 Miconazole 
               
               
                 Gentamicins 
                 Isoproterenol 
                 1-methyl-6-methoxy- 
               
               
                   
                   
                 dihydro-beta-carboline 
               
               
                 Metronidazole 
                 Diethylhexyl Phthalate 
                 Pentoxifylline 
               
               
                 Dichlorvos 
                 Cefaclor 
                 Tetrachlorodibenzodioxin 
               
               
                 Benzocaine 
                 dexchlorpheniramine 
                 4,5-dianilinophthalimide 
               
               
                 Luteinizing Hormone 
                 Niacin 
                 Trichloroepoxypropane 
               
               
                 ergocryptine 
                 ponasterone A 
                 diindolylmethane 
               
               
                 ciprofibrate 
                 Brefeldin A 
                 Chlorambucil 
               
               
                 Diazepam 
                 Megestrol Acetate 
                 Rolitetracycline 
               
               
                 Carbon Tetrachloride 
                 alpha-Tocopherol 
                 Azithromycin 
               
               
                 Quercetin 
                 Thalidomide 
                 Dimethylnitrosamine 
               
               
                 Concanavalin A 
                 Carbimazole 
                 Trimethadione 
               
               
                 Fluoxetine 
                 Progesterone 
                 Prednisone 
               
               
                 nateglinide 
                 fomepizole 
                 Cobalt 
               
               
                 Pemoline 
                 Phenol 
                 venlafaxine 
               
               
                 Ketoprofen 
                 dironyl 
                 Chlorpyrifos 
               
               
                 pimecrolimus 
                 meloxicam 
                 Cefuroxime 
               
               
                 Nitrazepam 
                 benziodarone 
                 Lincomycin 
               
               
                 acyline 
                 valdecoxib 
                 Cefotetan 
               
               
                 1,2,3-trichloropropane 
                 4-dichlorobenzene 
                 Mexiletine 
               
               
                 17-(allylamino)-17-demethoxygeldanamycin 
                 Ethambutol 
                 Halothane 
               
               
                 laudanosine 
                 fazarabine 
                 Cephalexin 
               
               
                 Methylnitrosourea 
                 Clofibrate 
                 Am 580 
               
               
                 Aspirin 
                 quetiapine 
                 2,4-diaminotoluene 
               
               
                 bevacizumab 
                 Mesna 
                 Carboplatin 
               
               
                 Eugenol 
                 2-(4-morpholinyl)-8-phenyl- 
                 Hydroxyurea 
               
               
                   
                 4H-1-benzopyran-4-one 
                   
               
               
                 1-(5-Isoquinolinesulfonyl)-2- 
                 bafilomycin A 
                 Bisoprolol 
               
               
                 Methylpiperazine 
                   
                   
               
               
                 N-(2-cyclohexyloxy-4- 
                 Ritodrine 
                 Ranitidine 
               
               
                 nitrophenyl)methanesulfonamide 
                   
                   
               
               
                 atorvastatin 
                 Dicyclomine 
                 Levobunolol 
               
               
                 Dipyridamole 
                 Diazinon 
                 Genistein 
               
               
                 HC toxin 
                 desloratadine 
                 Puromycin 
               
               
                 Labetalol 
                 Zidovudine 
                 scriptaid 
               
               
                 2-(1H-indazol-4-yl)-6-(4- 
                 lansoprazole 
                 Amitriptyline 
               
               
                 methanesulfonylpiperazin-1-ylmethyl)-4- 
                   
                   
               
               
                 morpholin-4-ylthieno(3,2-d)pyrimidine 
                   
                   
               
               
                 Captopril 
                 2,2′-(hydroxynitrosohydrazono)bis- 
                 Doxepin 
               
               
                   
                 ethanamine 
                   
               
               
                 bromopride 
                 vorinostat 
                 gabapentin 
               
               
                 CEP 14083 
                 Cimetidine 
                 Enalapril 
               
               
                 Diltiazem 
                 Methyl Methanesulfonate 
                 phenethyl isothiocyanate 
               
               
                 chlorcyclizine 
                 tenidap 
                 Lam ivudine 
               
               
                 hydroquinone 
                 efavirenz 
                 Isocarboxazid 
               
               
                 Colchicine 
                 6-hydroxy-2,5,7,8-tetramethylchroman- 
                 Clindamycin 
               
               
                   
                 2-carboxylic acid 
                   
               
               
                 Carbachol 
                 pirinixic acid 
                 Diflunisal 
               
               
                 Cisapride 
                 Cyclophosphamide 
                 Flurbiprofen 
               
               
                 Pentobarbital 
                 Bromocriptine 
                 Rifampin 
               
               
                 8-Bromo Cyclic Adenosine Monophosphate 
                 benzyloxycarbonylleucyl- 
                 Zimeldine 
               
               
                   
                 leucyl-leucine aldehyde 
                   
               
               
                 LBH589 
                 Norfloxacin 
                 Lisinopril 
               
               
                 Atovaquone 
                 Iproniazid 
                 Isoniazid 
               
               
                 letrozole 
                 N-acetylsphingosine 
                 Promazine 
               
               
                 Vidarabine 
                 Heparin 
                 8-aminohexylamino cAMP 
               
               
                 Propranolol 
                 Flupenthixol 
                 Fluorouracil 
               
               
                 Droperidol 
                 Amanitins 
                 marimastat 
               
               
                 Netilmicin 
                 Cyproheptadine 
                 Pergolide 
               
               
                 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine 
                 Ethionamide 
                 apicidin 
               
               
                 Losartan 
                 Atropine 
                 Mebendazole 
               
               
                 Secobarbital 
                 Saquinavir 
                 Topotecan 
               
               
                 Sulpiride 
                 Azauridine 
                 Clonidine 
               
               
                 sorafenib 
                 Oxyquinoline 
                 Terbutaline 
               
               
                 Hydrochlorothiazide 
                 dasatinib 
                 gemcitabine 
               
               
                 Calcitriol 
                   
                   
               
            
           
           
               
            
               
                 Y2. Molecules that downregulate PPAR-a: 
               
            
           
           
               
               
               
            
               
                 Primidone 
                 Trichloroacetic Acid 
                 Proglumide 
               
               
                 Tinidazole 
                 tropisetron 
                 Naloxone 
               
               
                 Streptozocin 
                 Capsaicin 
                 artemether 
               
               
                 Etodolac 
                 Hexachlorophene 
                 Ethisterone 
               
               
                 Gentian Violet 
                 bestatin 
                 Phenobarbital 
               
               
                 glimepiride 
                 Tetracycline 
                 vinorelbine 
               
               
                 Okadaic Acid 
                 Carotenoids 
                 paricalcitol 
               
               
                 Shiga Toxin 
                 valacyclovir 
                 Cortisone 
               
               
                 isopyrin 
                 versipelostatin 
                 marinobufagenin 
               
               
                 Altretamine 
                 oxiconazole 
                 Salicylic Acid 
               
               
                 Ifosfamide 
                 Cyproterone Acetate 
                 Sulfamethoxazole 
               
               
                 Cardiotoxins 
                 Caerulein 
                 Dextran Sulfate 
               
               
                 fludarabine 
                 senecionine 
                 Methylcellulose 
               
               
                 Amoxapine 
                 idebenone 
                 aceclofenac 
               
               
                 Aminosalicylic Acid 
                 Paclitaxel 
                 Doxapram 
               
               
                 Tunicamycin 
                 arsenic trioxide 
                 Cyclosporine 
               
               
                 Methiocarb 
                 Antipyrine 
                 Phenformin 
               
               
                 Benzethonium 
                 olanzapine 
                 anisindione 
               
               
                 lacidipine 
                 Heptachlor Epoxide 
                 3-deazaneplanocin 
               
               
                 Nystatin 
                 Phalloidine 
                 4-octylphenol 
               
               
                 Buformin 
                 pristane 
                 n-hexanal 
               
               
                 Rotenone 
                 Aflatoxins 
                 Lithium Carbonate 
               
               
                 Ethylnitrosourea 
                 Papaverine 
                 sunitinib 
               
               
                 decitabine 
                 Chloroquine 
                 blebbistatin 
               
               
                 Dimenhydrinate 
                 lomefloxacin 
                 Piperonyl Butoxide 
               
               
                 famciclovir 
                 doxofylline 
                 nimetazepam 
               
               
                 Isotretinoin 
                 Norepinephrine 
                 shikonin 
               
               
                 Stavudine 
                 Methoxsalen 
                 Plicamycin 
               
               
                 Vinblastine 
                 Kinetin 
                 Clemastine 
               
               
                 trichostatin A 
                 Deoxyglucose 
                 Cholecalciferol 
               
               
                 Glycine 
                 enterotoxin I, staphylococcal 
                 Allopurinol 
               
               
                 Tranexamic Acid 
                 bamipine 
                 Tacrolimus 
               
               
                 MF59 oil emulsion 
                 Azacitidine 
                 cerivastatin 
               
               
                 Tretinoin 
                 4-hydroxy-2-nonenal 
                 beta-glycerophosphoric acid 
               
               
                 Chlormadinone Acetate 
                 Dihydrotestosterone 
                 Mestranol 
               
               
                 candesartan 
                 Glycerol 
                 Canavanine 
               
               
                 benazepril 
                 Vancomycin 
                 Estriol 
               
               
                 Furosemide 
                 Phytohemagglutinins 
                 Benzo(a)pyrene 
               
               
                 Botulinum Toxins 
                 Nadolol 
                 Mitomycin 
               
               
                 monastrol 
                 Azoxymethane 
                 Aminocaproic Acids 
               
               
                 picotamide 
                 Immunoglobulin M 
                 polidocanol 
               
               
                 Ondansetron 
                 Methotrexate 
                 Bacitracin 
               
               
                 Insulin 
                 procyanidin 
                 loxoprofen 
               
               
                 isoascorbic acid 
                 Chlorhexidine 
                 Antimycin A 
               
               
                 Tetradecanoylphorbol Acetate 
                 naphthalene 
                 Lead 
               
               
                 infliximab 
                 Nimodipine 
                 adalimumab 
               
               
                 cineole 
                 Theophylline 
                 Bleomycin 
               
               
                 buflomedil 
                 Aflatoxin B1 
                 Mianserin 
               
               
                 bis(tri-n-butyltin)oxide 
                 Glipizide 
                 cilostazol 
               
               
                 Lorazepam 
                 Vecuronium Bromide 
                 carvedilol 
               
               
                 Dimethyl Sulfoxide 
                 Amiloride 
                 Malathion 
               
               
                 Ascorbic Acid 
                 Vincristine 
                 Tiapamil Hydrochloride 
               
               
                 Ethionine 
                 4-amino-6-hydrazino-7-beta-D- 
                 Buthionine Sulfoximine 
               
               
                   
                 ribofuranosyl-7H-pyrrolo(2,3-d)- 
                   
               
               
                   
                 pyrimidine-5-carboxamide 
                   
               
               
                 valsartan 
                 Echinomycin 
                 Phenylephrine 
               
               
                 Cycloheximide 
                 Y 27632 
                 Reserpine 
               
               
                 Isradipine 
                 Digitoxin 
                 Melphalan 
               
               
                 cyanoginosin LR 
                 Pregnenolone Carbonitrile 
                 tenoxicam 
               
               
                 SU 5402 
                 Penicillamine 
                 Acarbose 
               
               
                 Dactinomycin 
                 fasudil 
                 clopidogrel 
               
               
                 Palmitic Acid 
                 Paroxetine 
                 U 0126 
               
               
                 Loratadine 
                 Nitrendipine 
                 Chlordiazepoxide 
               
               
                 Prochlorperazine 
                 SC 514 
                 Terfenadine 
               
               
                 Nitric Oxide 
                 Ritonavir 
                 Gallamine Triethiodide 
               
               
                 Emetine 
                 Ramipril 
                 Tubocurarine 
               
               
                 Guanethidine 
                 Verapamil 
                 Prazosin 
               
               
                 Luteolin 
                 Buspirone 
                 enzastaurin 
               
               
                 Inosine Monophosphate 
                 Diphenhydramine 
                 Flunarizine 
               
               
                 Camptothecin 
                 resveratrol 
                 Galantamine 
               
               
                 Vitamin E 
                 Haloperidol 
                 Clozapine 
               
               
                 Kainic Acid 
                 SB 203580 
                 Atenolol 
               
               
                 pralidoxime 
                 Vitamin K 3 
                 Ionomyin 
               
               
                 Deferoxamine 
                 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-  
                 bortezomib 
               
               
                   
                 2-yl-1H-imidazol-2-yl)benzamide 
                   
               
               
                 Nocodazole 
               
               
                   
               
            
           
         
       
     
     All patents, patent applications, and publications cited herein are incorporated herein by reference in their entirety as if recited in full herein. 
     The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention and all such modifications are intended to be included within the scope of the following claims. 
     CITED DOCUMENTS 
     
         
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