Patent Publication Number: US-2022227750-A1

Title: Methods and compositions for prevention of anaphylaxis

Description:
This application is a continuation of U.S. patent application Ser. No. 14/335,829, filed Jul. 18, 2014, which claims priority to U.S. Provisional Patent Application Ser. No. 61/847,766, filed Jul. 18, 2013, the entire contents of each of which are incorporated by reference herein in their entirety. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with government support from National Institute of Allergy and Infectious Diseases, and this invention was made with government support under P50 CA058183, K08 HL085018-01A2, P50 CA097007, R21 CA149783, and R41 CA153658, awarded by National Institutes of Health. The United States Government has certain rights in the invention. 
    
    
     TECHNICAL FIELD 
     The present invention generally concerns at least the fields of cell biology, molecular biology, and medicine. 
     BACKGROUND 
     Anaphylaxis is a systemic hyperacute allergic reaction that causes more than 1,500 deaths per year in the United States. It is associated with intense vasodilatation and bronchoconstriction, severe laryngeal edema, drop of cardiac pressure, and hypothermia. 
     Anaphylaxis can occur in response to almost any foreign substance, although usual triggers include insect venom, foods, medication, and in some cases semen, latex, hormonal changes, or food additives. Physical factors, including exercise or temperature (either hot or cold) may also act as triggers because of their direct effects on mast cells. Exercise induced events are frequently associated with the ingestion of certain foods. In some cases, the cause is idiopathic. 
     The present disclosure satisfies a need in the art to provide novel compounds and methods for treating and/or preventing anaphylaxis or any mast-cell mediated allergic disorder in individuals. 
     SUMMARY 
     Embodiments of the disclosure include methods and compositions for the prevention and/or reduction in the risk or severity of an allergic reaction. In alternative embodiments, one or more compositions herein are useful for the treatment of allergic reaction. In embodiments of the invention, there are methods and compositions for the prevention and/or reduction in the risk or severity of any medical condition associated with mast cell degranulation. In specific embodiments, there are methods and compositions for the prevention and/or reduction in the risk or severity of anaphylaxis, anaphylactic shock, allergic rhinitis (hay fever), urticaria (hives), food allergy, drug allergy, hymenoptera allerga, bronchial constriction, asthma, eczema, and so forth. 
     Embodiments of the disclosure include methods and/or compositions for the prevention of an allergic reaction in an individual known to have the allergy, suspected of having the allergy, or at risk for having the allergy. The compositions include small molecules and functional derivatives as described herein. In some embodiments, the individual is receiving an additional therapy for the prevention and/or treatment of allergic reaction, including anaphylaxis. 
     In at least certain embodiments, an individual receives an effective amount of the composition for the inhibition of mast cell activity, such as the inhibition of mast cell degranulation. 
     In at least certain embodiments, an individual receives an effective amount of the composition as a preventative indication. The composition may be administered continually through the life of the patient following a realization of a need thereof. The composition may be administered only in anticipation of being in an environment that puts the individual at risk for being in need thereof. For example, the individual may be susceptible for allergic reaction (including anaphylaxis) from a particular food allergen but may be administered the composition prior to consumption of the food (days, hours, or minutes before consumption, for example). An individual with a susceptibility to allergic reaction to insect stings may be administered the composition prior to exposure to an environment or situation where the individual is at risk of being stung by the insect. An individual may be susceptible to allergic reaction because the allergen is only present in an environment of the individual in a seasonal pattern, and in such cases the individual may be administered the composition prior to and/or during the season. 
     In embodiments of the disclosure, an individual is given more than one dose of one or more compositions described herein or functional derivatives thereof. The dosing regimen may be separated in time by minutes, hours, days, months or years. 
     An individual in need thereof may be an individual that has at least one symptom of allergic reaction, is susceptible to having allergic reaction, has a biological marker for having allergic reaction but never been exposed to the allergen in a natural environment, or has had allergic reaction in the past. In certain cases, the individual has a family history of allergic reaction, including a family history of anaphylaxis; in such cases, the individual may or may not be known to have allergic reaction, including anaphylaxis. 
     Delivery of the composition of the invention may occur by any suitable route, including systemic or local, although in specific embodiments, the delivery route is oral, intravenous, topical, subcutaneous, intraarterial, intraperitoneal, buccal, and so forth, for example. 
     In particular embodiments, there is a method of inhibiting mast cell degranulation comprising exposing the mast cell(s) to one or more of the compositions disclosed herein or functional derivatives thereof. The mast cell(s) may be in vitro, ex vivo, or in vivo. The inhibition may be complete or may be reduced compared to the cells in the absence of exposure to the composition. In particular embodiments, the mast cells are in vivo in an individual known to have allergic reaction, at risk for allergic reaction, or that is susceptible to allergic reaction. 
     In some embodiments of the invention, the methods and/or compositions of the invention are useful for preventing and/or reducing the risk of or severity of allergic reaction (such as anaphylaxis), and in specific cases such action occurs by inhibiting Stat3 and/or Stat1 activity. In some embodiments of the invention, the methods and/or compositions of the invention are useful for preventing and/or reducing the risk of or severity of allergic reaction (such as anaphylaxis), and in specific cases such action occurs by inhibiting or reducing mast cell degranulation. In certain embodiments, the compositions inhibit Stat3 but fail to inhibit Stat1. In some embodiments, compounds of the invention interact with the Stat3 SH2 domain, competitively inhibit recombinant Stat3 binding to its immobilized pY-peptide ligand, and/or inhibit IL-6-mediated tyrosine phosphorylation of Stat3, for example. In particular embodiments, the compositions of the invention fulfills the criteria of interaction analysis (CIA): 1) global minimum energy score ≤−30; 2) formation of a salt-bridge and/or H-bond network within the pY-residue binding site of Stat3; and/or 3) formation of a H-bond with or blocking access to the amide hydrogen of E638 of Stat3, for example. In some embodiments, the composition(s) interacts with a hydrophobic binding pocket with the Stat3 SH2 domain. In some embodiments, the composition(s) inhibit the binding of Stat3 to its cognate phosphopeptide ligand. In some embodiments, the composition(s) inhibit cytokine-mediated Stat3 phosphorylation within cells. In some embodiments, the composition(s) inhibit nuclear translocation of Stat3 within cells. 
     In a specific embodiment of the invention, there is a method of preventing and/or reducing the risk or severity of allergic reaction (such as anaphylaxis) in an individual comprising delivering to the individual a therapeutically effective amount of a compound selected from the group consisting of N-(1′,2-dihydroxy-1,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide (which may be referred to as Cpd 188-9), N-(3,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(4,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(5,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(6,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(7,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(8,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, 4-Bromo-N-(1,6′-dihydroxy-[2,2′]binaphthalenyl-4-yl)-benzenesulfonamide, 4-Bromo-N-[4-hydroxy-3-(1H-[1,2,4]triazol-3-ylsulfanyl)-naphthalen-1-yl]-benzenesulfonamide, a functionally active derivative thereof, and a mixture thereof. 
     In a specific embodiment of the invention, there is a method of preventing and/or reducing the risk or severity of allergic reaction (such as anaphylaxis) in an individual comprising delivering to the individual a therapeutically effective amount of a compound selected from the group consisting of 4-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxo-1-propen-1-yl] benzoic acid; 4{5-[(3-ethyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-2-furyl}benzoic acid; 4-[({3-[(carboxymethyl)thio]-4-hydroxy-1-naphthyl}amino)sulfonyl]benzoic acid; 3-({2-chloro-4-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]-6-ethoxyphenoxy}methyl)benzoic acid; methyl 4-({[3-(2-methyoxy-2-oxoethyl)-4,8-dimethyl-2-oxo-2H-chromen-7-yl]oxy}methyl)benzoate; 4-chloro-3-{5-[(1,3-diethyl-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid; a functionally active derivative thereof; and a mixture thereof. In a specific embodiment, any of the compounds disclosed herein are suitable to treat and/or prevent allergic reaction, for example. 
     In another embodiment, the inhibitor comprises the general formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 2  may be the same or different and are selected from the group consisting of hydrogen, carbon, sulfur, nitrogen, oxygen, flourine, chlorine, bromine, iodine, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives. 
     In another embodiment of the invention, the composition comprises the general formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1 , and R 3  may be the same or different and are selected from the group consisting of hydrogen, carbon, nitrogen, sulfur, oxygen, flouring, chlorine, bromine, iodine, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives; and R 2  and R 4  may be the same or different and are selected from the group consisting of hydrogen, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives. 
     In another embodiment of the invention, the composition comprises the general formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , and R 3  may be the same or different and are selected from the group consisting of hydrogen, carbon, nitrogen, sulfur, oxygen, fluorine, chlorine, bromine, iodine, carboxyl, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives. 
     In other embodiments of the invention, there are methods of treating anaphylaxis in an individual wherein the composition(s) is an inhibitor of any members of the STAT protein family, including STAT1. STAT2. STAT3, STAT4, STAT5 (STAT5A and STAT5B), or STAT6, for example. 
     The foregoing has outlined rather broadly the features and technical advantages of the present invention in order that the detailed description of the invention that follows may be better understood. Additional features and advantages of the invention will be described hereinafter which form the subject of the claims of the invention. It should be appreciated by those skilled in the art that the conception and specific embodiment disclosed may be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present invention. It should also be realized by those skilled in the art that such equivalent constructions do not depart from the spirit and scope of the invention as set forth in the appended claims. The novel features which are believed to be characteristic of the invention, both as to its organization and method of operation, together with further objects and advantages will be better understood from the following description when considered in connection with the accompanying figures. It is to be expressly understood, however, that each of the figures is provided for the purpose of illustration and description only and is not intended as a definition of the limits of the present invention. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A -IG demonstrates inhibition of Stat3 binding to immobilized phosphopeptide ligand by compounds. Binding of recombinant Stat3 (500 nM) to a BiaCore sensor chip coated with a phosphododecapeptide based on the amino acid sequence surrounding Y1068 within the EGFR was measured in real time by SPR (Response Units) in the absence (0 μM) or presence of increasing concentrations (0.1 to 1,000 μM) of Cpd3 ( FIG. 1A ), Cpd30 ( FIG. 1B ), Cpd188 ( FIG. 1C ), Cpd3-2 ( FIG. 1D ), Cpd3-7 ( FIG. 1E ) and Cpd30-12 ( FIG. 1F ). Data shown are representative of 2 or more experiments. The equilibrium binding levels obtained in the absence or presence of compounds were normalized (response obtained in the presence of compound÷the response obtained in the absence of compound×100), plotted against the log concentration (nM) of the compounds ( FIG. 1G ). The experimental points fit to a competitive binding curve that uses a four-parameter logistic equation (see exemplary methods for details). These curves were used to calculate ICs % (Table 4). 
         FIGS. 2A-2F  demonstrates inhibition of IL-6-mediated activation of Stat3 by compounds. HepG2 cells were pretreated with DMSO alone or DMSO containing Cpd3 ( FIG. 2A ), Cpd188 ( FIG. 2B ), Cpd30 ( FIG. 2C ), Cpd3-2 ( FIG. 2D ), Cpd3-7 ( FIG. 2E ) or Cpd30-12 ( FIG. 2F ) at the indicated concentration for 60 min. Cells were then stimulated with IL-6 (30 ng/ml) for 30 min. Protein extracts of cells were separated by SDS-PAGE, blotted and developed serially with antibodies to pStat3, total Stat3 and β-actin. Blots were stripped between each antibody probing. The bands intensities of immunoblot were quantified by densitometry. The value of each pStat3 band&#39;s intensity was divided by each corresponding value of total Stat3 band intensity and the results normalized to the DMSO-treated control value and plotted as a function of the log compound concentration. The best-fit curves were generated based on 4 Parameter Logistic Model/Dose Response One Site/XLfit 4.2, IDBS. Each panel is representative of 3 or more experiments. 
         FIGS. 3A-3F  provides exemplary chemical formulas and names of compounds. The chemical formulas and names are indicated for Cpd3 ( FIG. 3A ), Cpd30 ( FIG. 3B ), Cpd188 ( FIG. 3C ), Cpd3-2 ( FIG. 3D ), Cpd3-7 ( FIG. 3E ) and Cpd30-12 ( FIG. 3F ). 
         FIG. 4  shows effect of compounds on Stat1 activation. HepG2 cells were pretreated with DMSO alone or DMSO containing each of the compounds at a concentration of 300 μM for 60 min. Cells were then stimulated with IFN-γ (30 ng/ml) for 30 min. Protein extracts of cells were separated by SDS-PAGE and immunoblotted serially with antibodies to pStat1, total Stat1 and β-actin. Blots were stripped between each immunoblotting. The results shown are representative of 2 or more experiments. 
         FIGS. 5A-5C  provides comparisons of the Stat3 and Stat1 SH2 domain sequences, 3-D structures and van der Waals energies of compound binding. Sequence alignment of Stat3 and Stat1 SH2 domains is shown in  FIG. 5A . The residues that bind the pY residue are highlighted in and pointed to by a solid arrow, the residue (E638) that binds to the +3 residue highlighted and pointed to by a dotted arrow and Loop βC-βD  and Loop αB-αC , which comprise the hydrophobic binding site consisting, are highlighted and pointed to by dot-dashed and dashed arrows, respectively.  FIG. 5B  shows an overlay of a tube-and-fog van der Waals surface model of the Stat3 SH2 domain and a tube-and-fog van der Waals surface model of the Stat1 SH2. The residues of the Stat3 SH2 domain represents Loop βC-βD  are highlighted and shown by dotted circles and the residues represent Loop αB-αC  are highlighted and shown by a dotted-dashed circle; the corresponding loop residues within the Stat1 SH2 domain are shown in a light fog surrounding the circles. This overlay is shown bound by Cpd3-7 as it would bind to the Stat3 SH2 domain. The van der Waals energy of each compound bound to the Stat1 SH2 domain or the Stat3 SH2 domain was calculated, normalized to the value for Stat1 and depicted in  FIG. 5C . 
         FIGS. 6A-6F  shows a computer model of each compound bound by the Stat3 SH2 domain. The results of computer docking to the Stat3 SH2 domain is shown for Cpd3 ( FIG. 6A ), Cpd30 ( FIG. 6B ), Cpd188 ( FIG. 6C ), Cpd3-2 ( FIG. 6D ), Cpd3-7 ( FIG. 6E ) and Cpd30-12 ( FIG. 6F ). The image on the left of each panel shows the compound binding to a spacefilling model of the Stat3 SH2 domain. The pY-residue binding site is represented by dashed circle, the +3 residue binding site is represented by a solid circle, loop Loop βC-βD  is represented by dotted circle and loop Loop αB-αC  is represented by dot-dashed circle. Residues R609 and K591 critical for binding pY are shown within a dashed circle, residue E638 that binds the +3 residue shown within a solid circle and the hydrophobic binding site consisting of Loop βC-βD  and LoopαB-αC is shown within a dash-dot and dotted circle, respectively. The image on the right side of each panel is a closer view of this interaction with hydrogen bonds indicated by dotted lines. In  FIG. 6A  the negatively charged benzoic acid moiety of Cpd3 has electrostatic interactions with the positively-charge pYresidue binding site consisting mainly of the guanidinium cation group of R609 and the basic ammonium group of K591. The benzoic acid group also forms a hydrogen-bond network consisting of double H-bonds between the carboxylic oxygen and the ammonium hydrogen of R609 and the amide hydrogen of E612. H-bond formation also occurs between the benzoic acid carbonyl oxygen and the side chain hydroxyl hydrogen of Serine 611. Within the +3 residue-binding site, the oxygen atom of 1,4-benzodioxin forms a hydrogen bond with the amide hydrogen of E638. In addition, the 2,3-dihydro-1,4-benzodioxin of Cpd3 interacts with the loops forming the hydrophobic binding site. In  FIG. 6B  the carboxylic terminus of the benzoic acid moiety of Cpd30, which is negatively charged under physiological conditions, forms a salt bridge with the guanidinium group of R609 within the pYresidue binding site. Within the +3 residue-binding site, the oxygen of the thiazolidin group forms a H-bond with the peptide backbone amide hydrogen of E638. In addition, the thiazolidin moiety plunges into the hydrophobic binding site. In  FIG. 6C  there is an electrostatic interaction between the (carboxymethyl) thio moiety of Cpd188 carrying a negative charge and the pY-residue binding site consisting of R609 and K591 carrying positive charge under physiological conditions. There are H-bonds between the hydroxyloxygen of the (carboxymethyl) thio group of Cpd188 and the guanidinium hydrogen of R609, between the hydroxyl-oxygen of the (carboxymethyl) thio group and the backbone amide hydrogen of E612, and between the carboxyl-oxygen of the (carboxymethyl) thio group of Cpd188 and the hydroxyl-hydrogen of S611. Within the +3 residue-binding site, there is a H-bond between the hydroxyl-oxygen of benzoic acid group of Cpd188 and the amide-hydrogen of E638. In addition, the benzoic acid group extends and interacts with the hydrophobic binding site. In  FIG. 6D  the benzoic acid group of Cpd3-2 has significant electrostatic interactions with the pY-residue binding site pocket, mainly contributed by R609 and K591, and forms two H bonds; the carboxylic oxygen of the benzoic acid group binds the guanidinium hydrogen of R609, and the carbonyl oxygen of the benzoic acid group binds to the carbonyl hydrogen of S611. Within the +3 residue-binding site, oxygen within the 1,3-dihydro-2H-inden-2-ylidene group forms an H bond to the backbone amide-hydrogen of E638. In addition, the 1,3-dihydro-2H-inden-2-ylidene group plunges into the hydrophobic binding site. In  FIG. 6E  H-bonds are formed between the carbonyl-oxygen of the methyl 4-benzoate moiety of Cpd 3-7 and the side chain guanidinium of R609 and between the methoxy-oxygen and the hydrogen of the ammonium terminus of K591. The (2-methoxy-2-oxoethyl)-4,8-dimethyl-2-oxo-2H-chromen group of Cpd3-7 blocks access to the amide hydrogen of E638 within the +3 residue-binding site. In addition, this group plunges into the hydrophobic binding site. In  FIG. 6F  there are electrostatic interactions between the benzoic acid derivative group of Cpd30-12 and R609 and 591 within the pY-residue binding site. Also, H-bonds are formed between the hydroxyl-oxygen of Cpd30-12 and the guanidinium-hydrogen of R609, between the carboxyl-oxygen of Cpd30-12 and the hydroxyl-hydrogen of S611 and between the furyl group of Cpd30-12 and the hydrogen of ammonium of K591. The 1,3-diethyl-4, 6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene groups blocks access to the +3 residue binding site; however, it extends into the groove between the pY-residue binding site and LoopβC-βD, while sparing the hydrophobic binding site. 
         FIGS. 7A-7B  shows inhibition of cytoplasmic-to-nuclear translocation of Stat3 assessed by confocal and high-throughput fluorescence microscopy. In  FIG. 7A . MEF/GFP-Stat3 cells grown on coverslips were pretreated with DMSO that either contained (row four) or did not contain (row three) Cpd3 (300 μM) for 60 min before being stimulated without (row one) or with IL-6 (200 ng/ml) and IL-6sR (250 ng/ml) for 30 minutes (rows two, three and four). Coverslips were examined by confocal fluorescent microscopy using filters to detect GFP (column one), DAPI (column two) or both (merge; column three). In  FIG. 7B , MEF-GFP-Stat3 cells were grown in 96-well plates with optical glass bottoms and pretreated with the indicated compound at the indicated concentrations in quadruplicate for 1 hour then stimulated with IL-6 (200 ng/ml) and IL-6sR (250 ng/ml) for 30 minutes. Cells were fixed and the plates were examined by high-throughput microscopy to determine the fluorescence intensity in the nucleus (FLIN) and the % ΔFLIN Max  was calculated as described in Example 1. Data shown are mean±SD and are representative of 2 or more studies. Best-fit curves were generated based on 4 Parameter Logistic Model/Dose Response One Site/XLfit 4.2. IDBS and were used to calculate IC 50  (Table 1). 
         FIG. 8  demonstrates inhibition of Stat3 DNA binding by compounds. Electrophoretic mobility shift assays were performed using whole-cell extracts prepared from HepG2 cells without and with stimulation with IL-6 (30 ng/ml) for 30 min. Protein (20 μg) was incubated with radiolabeled duplex oligonucleotide (hSIE) and DMSO without or with the indicated compounds (300 uM) for 60 minutes at 37° C. then separated by PAGE. The gel was dried and autoradiographed; the portion of the gel corresponding to the Stat3-bound hSIE band is shown. Data shown are representative of 2 studies. 
         FIG. 9  shows Cpd3, Cpd30 and Cpd188 and the hydrophobicity or hydrophilicity of the surface of the molecule. The dashed arrows point to hydrophilic surfaces, and the solid arrows point to hydrophobic surfaces. 
         FIG. 10  illustrates exemplary compound 3 (Cpd3). The top-left picture of  FIG. 11  shows Cpd3 docked into Stat3 and the interaction between Cpd3 and the surface of the protein and derivatives of Cpd3 that can fit into the surface of the protein. Stars represent atoms and chemical groups that can be replaced with other atoms or chemical groups to create one or more functional derivatives. The hydrophobic/hydrophilic surfaces of Cpd3 are also demonstrated on the top-right picture. The dashed arrows point to hydrophilic surfaces, and the solid arrows point to hydrophobic surfaces. R 1  and R2 could be identical or different and may comprise hydrogen, carbon, sulfur, nitrogen, oxygen, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, or benzoic acid-based derivatives. 
         FIG. 11  illustrates exemplary compound 30 (Cpd30). The top-left picture of  FIG. 12  shows Cpd30 docked into Stat3 and the interaction between Cpd30 and the surface of the protein, and derivatives of Cpd30 that fit into the surface of the protein. Stars represent atoms and chemical groups that can be replaced with other atoms or chemical groups to create one or more functional derivatives. The hydrophobic/hydrophilic surfaces of Cpd30 are also demonstrated on the top-right picture. The dashed arrows point to hydrophilic surfaces, and the solid arrows point to hydrophobic surfaces. 2-D structure of Cpd30 shown on the bottom picture. R 1 , R 2  R 3  and R 4  could identical or different and may comprise be hydrogen, carbon, sulfur, nitrogen, oxygen, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, or benzoic acid-based derivatives. 
         FIG. 12  illustrates exemplary compound 188 (Cpd188). The top picture of  FIG. 12  shows Cpd188 docked into Stat3 SH2 domain and the interaction between Cpd188 and the surface of the protein, and derivatives of Cpd188 that fit into the surface of the protein. Stars represent atoms and chemical groups that can be replaced with other atoms or chemical groups to create one ore more functional derivative. The hydrophobic/hydrophilic surfaces of Cpd188 are also demonstrated on the left picture on the bottom. The dashed arrows point to hydrophilic surfaces, and the solid arrows point to hydrophobic surfaces. Shown on the right bottom picture, R 1  and R 2  could be identical or different and may comprise hydrogen, carbon, sulfur, nitrogen, oxygen, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, or benzoic acid-based derivatives. 
         FIG. 13  illustrates schematic diagrams of Stat1 and Stat3. 
         FIG. 14  demonstrates that SPR IC 50  of 2nd generation Stat3 chemical probes is inversely correlated with 3-D pharmacophore score. 
         FIG. 15 , shows SPR IC 50  and AML apoptosis EC 50  of parent Cpd188 and two 2nd generation 188-like Stat3 chemical probes. 
         FIG. 16  provides an illustration of structure-activity relationships of 38 Cpd188-like, 2nd generation Stat3 probes. 
         FIG. 17  shows an exemplary modification scheme for 3rd generation Stat3 probe development using Cpd188-15 as a scaffold. 
         FIG. 18  provides illustration of the electrostatic surface of Stat3 SH2 domain (positive area in blue, neutral in white and negative in red in a color figure) and 20 docking poses of 5 (R=CH 2 PO 3   2− ), showing strong interactions between phosphonate groups (in purple and red) and K591/R609. 
         FIGS. 19A and 19B .  FIG. 19A  shows physician diagnosed food allergies in healthy volunteers, AD-HIES, and atopic control patients were determined by interview.  FIG. 19B  demonstrates incidence of physician diagnosed anaphylaxis in AD-HIES and atopic control patients. Significance determined by a two-tailed Chi-squared test. 
         FIGS. 20A and 20B .  FIG. 20A  shows that mast cell degranulation was measured by FcεRI crosslinking and subsequent β-hexosaminidase release in LAD2 cells transduced with five different shRNAs against STAT3. Data representative of two independent experiments. LAD2=unstimulated control, LAD+=FcεRI crosslinking.  FIG. 20B  shows that mast cell degranulation was measured by FcεRI crosslinking and subsequent β-hexosaminidase release in primary human mast cells transduced with two different shRNAs against STAT3. HuMC=unstimulated control, HuMC+=FcεRI crosslinking. 
         FIG. 21  demonstrates correlation between STAT23 knockdown and inhibition of mast cell degranulation (r 2 =0.9463). 
         FIG. 22  demonstrates effective treatment in an anaphylaxis model using Cpd188-9. 
         FIG. 23  provides a dose response curve using different dosages of Cpd188-9 in an anaphylaxis model utilizing beta-hexosaminidase (% release) as a measure of mas cell degranulation. 
         FIG. 24  shows that systemic anaphylaxis was prevented in vivo with an exemplary STAT3 inhibitor. 
         FIG. 25  demonstrates that peripheral and central vascular leakage is decreased by Cpd 188-9. 
         FIG. 26  illustrates the effect of Cpd188-9 is not because of a decreased mast cell degranulation in vivo. 
         FIG. 27  demonstrates the effect of Cpd 188-9 on Ag-induced degranulation in murine mast cells. 
         FIG. 28  illustrates an exemplary transwell permeability assay. 
         FIG. 29  shows that Cpd188-9 pretreated (as an example, for 7 days) HUVECS resistant to histamine-induced permeability. 
         FIG. 30  shows HIES mouse is resistant to anaphylaxis (Siegel et al., JACI, 2013). 
         FIG. 31  demonstrates STAT3 mutant (HIES6) HUVECS resistant to histamine-induced permeability. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. 
     In some embodiments, there is a method of preventing, and/or reducing the risk or severity of allergic reaction (such as anaphylaxis) in an individual, comprising delivering to the individual one or more particular compounds. In some embodiments, the compound(s) is a STAT3 inhibitor. In certain embodiments the compound(s) is not a STAT3 inhibitor. In particular cases, the compound(s) is a STAT1 inhibitor, but in particular cases it is not a STAT1 inhibitor. In certain aspects, there are some compounds that are both STAT3 and STAT1 inhibitors or is neither a STAT3 or STAT1 inhibitor. In some cases, the composition is a mast cell inhibitor, including a mast cell degranulation inhibitor. 
     In certain embodiments of the invention, there is a compound for use in the prevention and/or reduction in risk or severity of allergic reaction (such as anaphylaxis), wherein the compound is selected from the group consisting of N-(1,2-dihydroxy-1,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide, N-(3,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(4,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(5,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(6,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(7,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(8,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, 4-Bromo-N-(1,6′-dihydroxy-[2,2′]binaphthalenyl-4-yl)-benzenesulfonamide, 4-Bromo-N-[4-hydroxy-3-(1H-[1,2,4]triazol-3-ylsulfanyl)-naphthalen-1-yl]-benzenesulfonamide, or a combination thereof, a functionally active derivative, and a mixture thereof. 
     In certain embodiments of the invention, there is a compound for use in the prevention and/or reduction in risk of allergic reaction (such as anaphylaxis), wherein the compound is selected from the group consisting of 4-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxo-1-propen-1-yl] benzoic acid; 4{5-[(3-ethyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-2-furyl}benzoic acid; 4-[({3-[(carboxymethyl)thio]-4-hydroxy-1-naphthyl}amino)sulfonyl] benzoic acid; 3-({2-chloro-4-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]-6-ethoxyphenoxy}methyl)benzoic acid; methyl 4-({[3-(2-methyoxy-2-oxoethyl)-4,8-dimethyl-2-oxo-2H-chromen-7-yl]oxy}methyl)benzoate; 4-chloro-3-{5-[(1,3-diethyl-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid; a functionally active derivative and a mixture thereof. In a specific embodiment of the invention, the composition is a Stat3 inhibitor but does not inhibit Stat1. The composition may be a mast cell degranulation inhibitor. 
     In a specific embodiment of the invention, the composition is delivered in vivo in a mammal. In another embodiment the mammal is a human. In another specific embodiment the human is known to have anaphylaxis, is suspected of having anaphylaxis, or is at risk for developing anaphylaxis. In another embodiment, the human is known to have anaphylaxis and is receiving an additional therapy for the anaphylaxis. Composition(s) of the disclosure prevent and/or reduce the risk or severity of allergic reaction, in particular embodiments. 
     I. Definitions 
     As used herein the specification. “a” or “an” may mean one or more. As used herein in the claim(s), when used in conjunction with the word “comprising”, the words “a” or “an” may mean one or more than one. As used herein “another” may mean at least a second or more. Still further, the terms “having”, “including”, “containing” and “comprising” are interchangeable and one of skill in the art is cognizant that these terms are open ended terms. Some embodiments of the invention may consist of or consist essentially of one or more elements, method steps, and/or methods of the invention. It is contemplated that any method or composition described herein can be implemented with respect to any other method or composition described herein. 
     The term “inhibitor” as used herein refers to one or more molecules that interfere at least in part with the activity of Stat3 to perform one or more activities, including the ability of Stat3 to bind to a molecule and/or the ability to be phosphorylated. In alternative embodiments, an inhibitor reduces the level of degranulation of mast cells, which may be measured in vitro by % release of beta-hexosaminidase or other mast cell mediators such as cytokines, histamine, leukotrienes, etc. The level of degranulation of mast cells may be measured in vivo in a multitude of allergy and anaphylaxis models that primarily measure core temperature reductions with acute challenge, vascular permeability, inflammation, or systemic mast cell mediators, such as histamine or tryptase. 
     The phrase “therapeutically effective amount” as used herein means that amount of a compound, material, or composition comprising a compound of the present invention that is effective for producing some desired therapeutic effect, e.g., treating (i.e., preventing and/or ameliorating) allergic reaction in a subject, or inhibiting protein-protein interactions mediated by an SH2 domain in a subject, at a reasonable benefit/risk ratio applicable to any medical treatment. In one embodiment, the therapeutically effective amount is enough to reduce or eliminate at least one symptom. One of skill in the art recognizes that an amount may be considered therapeutically effective even if the allergic reaction is not totally eradicated but improved partially. For example, a symptom from the allergic reaction may be partially reduced or completed eliminated, and so forth. 
     The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. 
     The phrase “at risk for having allergic reaction” as used herein refers to an individual that has had an allergic reaction before, has one or more family members with allergic reaction history, or is a child. 
     As used herein. “binding affinity” refers to the strength of an interaction between two entities, such as a protein-protein interaction. Binding affinity is sometimes referred to as the K a , or association constant, which describes the likelihood of the two separate entities to be in the bound state. Generally, the association constant is determined by a variety of methods in which two separate entities are mixed together, the unbound portion is separated from the bound portion, and concentrations of unbound and bound are measured. One of skill in the art realizes that there are a variety of methods for measuring association constants. For example, the unbound and bound portions may be separated from one another through adsorption, precipitation, gel filtration, dialysis, or centrifugation, for example. The measurement of the concentrations of bound and unbound portions may be accomplished, for example, by measuring radioactivity or fluorescence, for example. K a  also can be inferred indirectly through determination of the K i  or inhibitory constant. Determination of the K i  can be made several ways for example by measuring the K a  of STAT3 binding to its phosphopeptide ligand within the EGFR at position Y1068 and by measuring the concentration of a molecule that reduces binding of STAT3 by 50%. In certain embodiments of the invention, the binding affinity of a Stat3 inhibitor for the SH2 domain of Stat3 is similar to or greater than the affinity of the compounds listed herein. 
     The term “domain” as used herein refers to a subsection of a polypeptide that possesses a unique structural and/or functional characteristic; typically, this characteristic is similar across diverse polypeptides. The subsection typically comprises contiguous amino acids, although it may also comprise amino acids that act in concert or that are in close proximity due to folding or other configurations. An example of a protein domain is the Src homology 2 (SH2) domain of Stat3. The term “SH2 domain” is art-recognized, and, as used herein, refers to a protein domain involved in protein-protein interactions, such as a domain within the Src tyrosine kinase that regulates kinase activity. The invention contemplates modulation of activity, such as activity dependent upon protein-protein interactions, mediated by SH2 domains of proteins (e.g., tyrosine kinases such as Src) or proteins involved with transmission of a tyrosine kinase signal in organisms including mammals, such as humans. 
     As used herein, a “mammal” is an appropriate subject for the method of the present invention. A mammal may be any member of the higher vertebrate class Mammalia, including humans; characterized by live birth, body hair, and mammary glands in the female that secrete milk for feeding the young. Additionally, mammals are characterized by their ability to maintain a constant body temperature despite changing climatic conditions. Examples of mammals are humans, cats, dogs, cows, mice, rats, and chimpanzees. Mammals may be referred to as “patients” or “subjects” or “individuals”. 
     II. General Embodiments 
     General embodiments include one or more compositions for the prevention of allergic reaction and methods of their use. An individual in need of allergic reaction prevention, including reduction in the severity of at least one symptom of allergic reaction, is provided with an effective amount of one or more compositions as disclosed herein. Although any composition disclosed herein may be suitable, in specific embodiments the composition is N-(1′,2-dihydroxy-1,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide (Cpd 188-9) or a functional derivative thereof. 
     In some cases an individual prevents the allergic reaction or reduces the severity of the allergic reaction with one or more compositions as disclosed herein by intaking the composition routinely, such as routinely after having a first allergic reaction or after identifying the risk of having an allergic reaction (such as by a standard allergy test, for example). The term “routinely” may be described as a regular course of procedure, such as once or more than once daily, biweekly, weekly, monthly, and so forth, for example. 
     In some cases, an individual prevents the allergic reaction or reduces the severity of the allergic reaction with one or more compositions as disclosed herein by intaking the composition periodically, such as periodically after having a first allergic reaction or after identifying the risk of having an allergic reaction (such as by a standard allergy test, for example). The period may be one or more seasons of the year. The period may be one or more periods of time for one or more increased allergens in an environment, such as during pollination of one or more types of plants, for example. 
     In some cases, an individual prevents the allergic reaction or reduces the severity of the allergic reaction with one or more compositions as disclosed herein by intaking the composition prior to an event or environment or condition where the individual is likely to be or known to be exposed to the allergen. For example, the individual may be administered the composition prior to consumption of a particular food allergen, prior to close proximity to or exposure to a particular plant allergen, prior to exposure to an environment having stinging insects, prior to an exposure to latex, prior to sexual intercourse, and so forth. 
     In some cases, an individual may intake the composition routinely but may take an increased dosage of the composition prior to an event or environment or condition where the individual is likely to be or known to be exposed to the allergen. 
     In some cases, an individual may intake the composition periodically but may take an increased dosage of the composition prior to an event or environment or condition where the individual is likely to be or known to be exposed to the allergen. 
     In certain cases, an individual is receiving, has received, and/or will receive an effective dosage of one or more compositions of the disclosure, but the individual will also receive another medical composition for the allergic reaction. In some cases, the other medical composition may be one or more doses of an antihistamine, steroids epinephrine, or a combination thereof, for example. 
     In cases wherein an individual has at least one symptom of allergic reaction, the individual may be provided with an effective amount of one or more compositions of the invention prior to and/or after the appearance of allergic reaction. When the individual is provided one of more compositions prior to the appearance of allergic reaction, the onset of allergic reaction may be delayed or completely inhibited and/or the severity of the allergic reaction may be reduced, compared to the condition of the individual without having received the composition(s), for example. 
     In particular embodiments, an individual has been diagnosed with allergic reaction, and methods of the invention may include steps of diagnosing of the allergic reaction in the individual. An individual may be tested for allergic reaction by standard means in the art. For example, one can perform skin tests (where a small amount of a suspected allergen is placed on or below the skin to see if a reaction develops) and/or blood tests for antibodies to the allergen, such as using ELISA to measure IgE. Such test may be performed before or after it is known that the individual has one or more allergies or that the individual has had an allergic reaction. 
     III. Allergic Reaction 
     Embodiments of the invention concern compositions and methods for treatment and/or prevention or reduction in the risk of any kind of allergic reaction. An allergic reaction is a hypersensitivity disorder of the immune system in which a person&#39;s immune system reacts to a normally harmless substance (an allergen), such as from the environment. Allergic reactions are characterized by excessive activation of mast cells and basophils by Immunoglobulin E (IgE), and the reaction results in an inflammatory response with a range from discomfort to being fatal. 
     Any type of allergic reaction may be addressed with one or more compositions as disclosed herein. The allergic reaction may be anaphylaxis, anaphylactic shock, allergic rhinitis (hay fever), urticaria (hives), food allergy, drug allergy, hymenoptera allerga, bronchial constriction, asthma, eczema, and so forth. The compositions as disclosed herein are useful for prevention of one or more of these allergic reactions or for the reduction in the risk or severity of one or more of these allergic reactions. 
     In specific embodiments, the allergic reaction is anaphylaxis, which is characterized by rapid onset and can be fatal. It typically causes a number of symptoms including an itchy rash, throat swelling, and low blood pressure, for example. Common causes include insect bites/stings, foods, and medications. 
     On a pathophysiologic level, anaphylaxis is caused by the release of mediators from mast cells, such as by the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes non-immunologic mechanism. In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcεRI receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and cause heart muscle depression. Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils. 
     Anaphylaxis typically presents with many different symptoms over minutes or hours. The most common affected areas include the skin, respiratory system, gastrointestinal system, heart and vasculature, and central nervous system and often include more than one system or organ. 
     Skin symptoms usually include generalized hives, itchiness, flushing, and/or swelling of the afflicted tissues. The tongue may swell, and some experience a runny nose and swelling of the conjunctiva. The skin may also be blue tinted because of reduced oxygen. Respiratory symptoms include shortness of breath, wheezing, or stridor, hoarseness, pain with swallowing, and/or a cough. Cardiac symptoms include coronary artery spasm, myocardial infarction, dysrhythmia, cardiac arrest, changes in heart rate, and/or a drop in blood pressure or shock. Gastrointestinal symptoms may include crampy abdominal pain, diarrhea, vomiting, confusion, a loss of bladder control and/or pelvic pain similar to that of uterine cramps. 
     Anaphylaxis may be diagnosed based on clinical criteria, such as when within minutes or hours of exposure to an allergen there is involvement of the skin or mucosal tissue in addition to either respiratory difficulty or a low blood pressure. In certain cases anaphylaxis is diagnosed with two or more of the following symptoms: a. involvement of the skin or mucosa; b. respiratory difficulties; c. low blood pressure; and d. gastrointestinal symptoms. Low blood pressure after exposure to a known allergen may be involved. Diagnosis may include blood tests for tryptase or histamine (released from mast cells) for anaphylaxis because of insect stings or medications. 
     There are three main classifications of anaphylaxis, all of which may be preventable or reduced in severity with one or more compositions as disclosed herein: anaphylactic shock; biphasic anaphylaxis; and pseudoanaphylaxis or anaphylactoid reactions (which are a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation and may be referred to as non-immune anaphylaxis). 
     In certain embodiments, an individual in need thereof is provided one or more compositions as disclosed herein but also is exposed to desensitization. 
     Individual with food allergies are suitable for exposure to one or more compositions as disclosed herein. Typical food allergens include milk, legumes (such as peanuts), shellfish, tree nuts, eggs, fish, soy, and wheat, for example. Severe cases are usually caused by ingesting the allergen, but some people experience a severe reaction upon contact and/or close proximity. 
     Individual with medication allergies are suitable for exposure to one or more compositions as disclosed herein. Any medication may potentially trigger allergic reaction, including anesthetics. β-lactam antibiotics, aspirin, NSAIDs, chemotherapy, vaccines, protamine and herbal preparations. Some medications (such as vancomycin, morphine, or x-ray contrast) cause anaphylaxis by directly triggering mast cell degranulation. 
     Individuals with venom allergies are suitable for exposure to one or more compositions as disclosed herein. Venom from stinging or biting animals (such as Hymenoptera (bees and wasps), jellyfish, sting ray) may induce anaphylaxis in susceptible people. Individuals with previous systemic reactions (anything more than a local reaction around the site of the sting) are at risk for future anaphylaxis, although some individuals have had no previous systemic reaction. 
     In some cases, people that have had one type of allergic reaction are also susceptible to having another type of allergic reaction, and these individual may receive effective amounts of one or more compositions as disclosed herein. 
     Allergic reaction symptoms can develop quickly, often within seconds or minutes. They may include the following: abdominal pain; abnormal (high-pitched) breathing sounds; anxiety; chest discomfort or tightness; cough; diarrhea; difficulty breathing; difficulty swallowing; dizziness or light-headedness; hives; itchiness; nasal congestion; nausea or vomiting; palpitations; skin redness; slurred speech; swelling of the face, eyes, or tongue; unconsciousness; wheezing; rapid pulse, arrhythmia; pulmonary edema; low blood pressure; blue skin; weakness; and/or wheezing. 
     U.S. Pat. No. 8,099,167, which is incorporated by reference herein, describes methods and devices for treating anaphylaxis, anaphylactic shock, bronchial constriction, and/or asthma. 
     IV. Compositions 
     Embodiments of the invention encompass compositions that are useful for preventing and/or reducing the risk or severity of allergic reaction (such as anaphylaxis). Specific compositions are disclosed herein, but one of skill in the art recognizes that functional derivatives of such compositions are also encompassed by the invention. The term “derivative” as used herein is a compound that is formed from a similar compound or a compound that can be considered to arise from another compound, if one atom is replaced with another atom or group of atoms. Derivative can also refer to compounds that at least theoretically can be formed from the precursor compound. 
     In particular embodiments, compositions and functionally active derivatives as described herein are utilized in treatment and/or prevention of anaphylaxis. Specific but nonlimiting examples of different R groups for the compositions are provided in Tables 1, 2, and 3. 
     The term “functionally active derivative” or “functional derivative” is a derivative as previously defined that retains the function of the compound from which it is derived. In one embodiment of the invention, a derivative of N-(1′,2-dihydroxy-1,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide, N-(3,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(4,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(5,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(6,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(7,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(8,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, 4-Bromo-N-(1,6′-dihydroxy-[2,2′]binaphthalenyl-4-yl)-benzenesulfonamide, 4-Bromo-N-[4-hydroxy-3-(1H-[1,2,4]triazol-3-ylsulfanyl)-naphthalen-1-yl]-benzenesulfonamide, 4-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxo-1-propen-1-yl] benzoic acid, 4{5-[(3-ethyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-2-furyl}benzoic acid, 4-[({3-[(carboxymethyl)thio]-4-hydroxy-1-naphthyl}amino)sulfonyl] benzoic acid, 3-({2-chloro-4-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]-6-ethoxyphenoxy}methyl)benzoic acid, methyl 4-({[3-(2-methyoxy-2-oxoethyl)-4,8-dimethyl-2-oxo-2H-chromen-7-yl]oxy)methyl)benzoate, or 4-chloro-3-{5-[(1,3-diethyl-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl)benzoic acid retains Stat3 inhibitory activity. In another embodiment of the invention, a derivative of 4-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxo-1-propen-1-yl] benzoic acid, 4{5-[(3-ethyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-2-furyl}benzoic acid, 4-[({3-[(carboxymethyl)thio]-4-hydroxy-1-naphthyl}amino)sulfonyl]benzoic acid, 3-({2-chloro-4-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]-6-ethoxyphenoxy}methyl)benzoic acid, methyl 4-({[3-(2-methyoxy-2-oxoethyl)-4,8-dimethyl-2-oxo-2H-chromen-7-yl]oxy}methyl)benzoate, or 4-chloro-3-{5-[(1,3-diethyl-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid retains Stat3 inhibitory activity and, in specific embodiments, also retains non-inhibition of Stat1, although in some cases it may also inhibit Stat1. 
     In a specific embodiment of the invention, there is a method of preventing or reducing the risk or severity of allergic reaction (such as anaphylaxis) in an individual comprising delivering to the individual a compound selected from the group consisting of N-(1′,2-dihydroxy-1,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide, N-(3,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(4,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(5,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(6,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(7,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, N-(8,1′-Dihydroxy-[1,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide, 4-Bromo-N-(1,6′-dihydroxy-[2,2′]binaphthalenyl-4-yl)-benzenesulfonamide, 4-Bromo-N-[4-hydroxy-3-(1H-[1,2,4]triazol-3-ylsulfanyl)-naphthalen-1-yl]-benzenesulfonamide, 4-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxo-1-propen-1-yl] benzoic acid 4{5-[(3-ethyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-2-furyl}benzoic acid, 4-[({3-[(carboxymethyl)thio]-4-hydroxy-1-naphthyl}amino)sulfonyl] benzoic acid, 3-({2-chloro-4-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]-6-ethoxyphenoxy}methyl)benzoic acid, methyl 4-({[3-(2-methyoxy-2-oxoethyl)-4,8-dimethyl-2-oxo-2H-chromen-7-yl]oxy}methyl)benzoate, 4-chloro-3-{5-[(1,3-diethyl-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid, and a mixture thereof. 
     In another embodiment, the composition comprises the general formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 2  may be the same or different and are selected from the group consisting of hydrogen, carbon, sulfur, nitrogen, oxygen, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives. 
     In another embodiment of the invention, the composition comprises the general formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1 , and R 3  may be the same or different and are selected from the group consisting of hydrogen, carbon, nitrogen, sulfur, oxygen, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives, and R 2  and R 4  may be the same or different and are selected from the group consisting of hydrogen, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives. 
     In another embodiment of the invention, the composition comprises the general formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , and R 3  may be the same or different and are selected from the group consisting of hydrogen, carboxyl, alkanes, cyclic alkanes, alkane-based derivatives, alkenes, cyclic alkenes, alkene-based derivatives, alkynes, alkyne-based derivative, ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives, carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters and ester-based derivatives, amines, amino-based derivatives, amides, amide-based derivatives, monocyclic or polycyclic arene, heteroarenes, arene-based derivatives, heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid, and benzoic acid-based derivatives. 
     An exemplary and illustrative list of alkanes, cyclic alkanes, and alkane-based derivates are described herein. Non-limiting examples of ketones, ketone-based derivatives, aldehydes, aldehyde-based derivatives; carboxylic acids, carboxylic acid-based derivatives, ethers, ether-based derivatives, esters, ester-based derivatives, amines, amino-based derivatives, amides, and amide-based derivatives are listed herein. Exemplary monocyclic or polycyclic arene, heteroarenes, arene-based or heteroarene-based derivatives, phenols, phenol-based derivatives, benzoic acid and benzoic acid-based derivatives are described herein. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 1 
               
               
                   
                   
               
               
                   
                 Chemical names 
                 Formulas 
               
               
                   
                   
               
             
            
               
                   
                 Methyl 
                 CH 3   
               
               
                   
                 Ethyl 
                 C 2 H 5   
               
               
                   
                 Vinyl (ethenyl) 
                 C 2 H 3   
               
               
                   
                 Ethynyl 
                 C 2 H 
               
               
                   
                 Cyclopropyl 
                 C 3 H 5   
               
               
                   
                 Cyclobutyl 
                 C 4 H 7   
               
               
                   
                 Cyclopentyl 
                 C 5 H 9   
               
               
                   
                 Cyclohexyl 
                 C 6 H 11   
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 Chemical names 
                 Chemical formulas 
               
               
                   
                   
               
             
            
               
                   
                 Acetonyl 
                 C 3 H 5 O 
               
               
                   
                 Methanal (formaldehyde) 
                 CH 2 O 
               
               
                   
                 Paraldehyde 
                 C 6 H 12 O 3   
               
               
                   
                 Ethanoic acid 
                 CH 3 COOH 
               
               
                   
                 Diethyl ether 
                 C 4 H 10 O 
               
               
                   
                 Trimethylamine 
                 C 3 H 9 N 
               
               
                   
                 Acetamide 
                 C 2 H 5 NO 
               
               
                   
                 Ethanol 
                 C 2 H 5 OH 
               
               
                   
                 Methanol 
                 CH 3 OH 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 3 
               
               
                   
                   
               
               
                   
                 Chemical names 
                 Chemical formulas 
               
               
                   
                   
               
             
            
               
                   
                 Benzol 
                 C 6 H 6   
               
               
                   
                 Phenol 
                 C 6 H 6 O 
               
               
                   
                 Benzoic acid 
                 C 7 H 6 O 2   
               
               
                   
                 Aniline 
                 C 6 H 7 N 
               
               
                   
                 Toluene 
                 C 7 H 8   
               
               
                   
                 Pyridazine 
                 C 4 H 4 N 2   
               
               
                   
                 Pyrimidine 
                 C 4 H 4 N 2   
               
               
                   
                 Pyrazine 
                 C 4 H 4 N 2   
               
               
                   
                 Biphenyl 
                 C 12 H 10   
               
               
                   
                   
               
            
           
         
       
     
     The compositions of the present invention and any functionally active derivatives thereof may be obtained by any suitable means. In specific embodiments, the derivatives of the invention are provided commercially, although in alternate embodiments the derivatives are synthesized. The chemical synthesis of the derivatives may employ well known techniques from readily available starting materials. Such synthetic transformations may include, but are not limited to protection, de-protection, oxidation, reduction, metal catalyzed C—C cross coupling, Heck coupling or Suzuki coupling steps (see for example, March&#39;s Advanced Organic Chemistry: Reactions, Mechanisms, and Structures. 5 th  Edition John Wiley and Sons by Michael B. Smith and Jerry March, incorporated here in full by reference). 
     V. Embodiments for Targeting Stat3 
     STAT proteins, of which there are seven (1, 2, 3, 4, 5A, 5B and 6), transmit peptide hormone signals from the cell surface to the nucleus. Detailed structural information of STAT proteins currently is limited to Stat1 and Stat3. Stat1 was the first STAT to be discovered (Fu et al., 1992) and is required for signaling by the Type I and II IFNs (Meraz et al., 1996; Wiederkehr-Adam et al., 2003; Durbin et al., 1996; Haan et al., 1999). Studies in Stat1-deficient mice (Meraz et al., 1996; Durbin et al., 1996; Ryan et al., 1998) support an essential role for Stat1 in innate immunity, notably against viral pathogens. In addition, Stat1 is a potent inhibitor of growth and promoter of apoptosis (Bromberg and Darnell, 2000). Also, because tumors from carcinogen-treated wild-type animals grow more rapidly when transplanted into the Stat1-deficient animals than they do in a wild-type host, Stat1 contributes to tumor surveillance (Kaplan et al., 1998). 
     Stat3 was originally termed acute-phase response factor (APRF) because it was first identified as a transcription factor that bound to IL-6-response elements within the enhancer-promoter region of various acute-phase protein genes (Akira, 1997). In addition to receptors for the IL-6 cytokine family, other signaling pathways are linked to Stat3 activation include receptors for other type I and type II cytokine receptors, receptor tyrosine kinases, G-protein-coupled receptors and Src kinases (Schindler and Darnell, 1995; Turkson et al., 1998). Targeted disruption of the mouse Stat3 gene leads to embryonic lethality at 6.5 to 7.5 days (Takeda et al., 1997) indicating that Stat3 is essential for early embryonic development possibly gastrulation or visceral endoderm function (Akira, 2000). Tissue-specific deletion of Stat3 using Cre-lox technology has revealed decreased mammary epithelial cell apoptosis resulting in delayed breast involution during weaning (Chapman et al., 1999). Recent findings indicate that switching of the predominant STAT protein activated by a given receptor can occur when a STAT downstream of that receptor is genetically deleted (Costa-Pereira et al, 2002; Qing and Stark, 2004). These findings suggest the possibility that the effect of Stat3 deletion in breast tissue may be mediated indirectly by increased activation of other STAT proteins, especially Stat5. 
     Stat1 and Stat3 isoforms. Two isoforms of Stat1 and Stat3 have been identified-α (p91 and p92, respectively) and β (p84 and p83, respectively) (Schindler et al., 1992; Schaefer et al., 1995; Caldenhoven et al., 1996; Chakraborty et al., 1996)—that arise due to alternative mRNA splicing ( FIG. 13 ). In contrast to Stat1β (712 aa), in which the C-terminal transactivation is simply deleted, the 55 amino acid residues of Stat3α are replaced in Stat3β by 7 unique amino acid residues at its C-terminus. Unlike Stat1β, Stat3β is not simply a dominant-negative of Stat3α (Maritano et al., 2004) and regulates gene targets in a manner distinct from Stat3β (Maritano et al., 2004; Yoo et al., 2002). Stat3α has been demonstrated to contribute to transformation in cell models and many human cancers including breast cancer. Stat3α was shown to be constitutively activated in fibroblasts transformed by oncoproteins such as v-Src (Yu et al., 1995; Garcia and Jove, 1998) and to be essential for v-Src-mediated transformation (Turkson et al., 1998; Costa-Pereira et al., 2002). In contrast to Stat3α, Stat3β antagonized v-Src transformation mediated through Stat3α (Turkson et al., 1998). Overexpression of a constitutively active form of Stat3α in immortalized rat or mouse fibroblasts induced their transformation and conferred the ability to form tumors in nude mice (Bromberg et al., 1999). Stat3 has been shown to be constitutively activated in a variety of hematological and solid tumors including breast cancer (Dong et al., 2003; Redell and Tweardy, 2003) as a result of either autocrine growth factor production or dysregulation of protein tyrosine kinases. In virtually all cases, the isoform demonstrating increased activity is Stat3α. 
     Targeting Stat3α while sparing Stat1. Given its multiple contributory roles to oncogenesis, Stat3 has recently gained attention as a potential target for cancer therapy (Bromberg, 2002; Turkson, 2004). While several methods of Stat3 inhibition have been employed successfully and have established proof-of-principle that targeting Stat3 is potentially beneficial in a variety of tumor systems including breast cancer in which Stat3 is constitutively activated (Epling-Burnette et al., 2001; Yoshikawa et al., 2001; Li and Shaw, 2002; Catlett-Falcone et al., 1999; Mora et al., 2002; Grandis et al., 2000; Leong et al., 2003; Jing et al., 2003; Jing et al., 2004; Turkson et al., 2001; Ren et al., 2003; Shao et al., 2003; Turkson et al., 2004; Uddin et al., 2005); all have potential limitations for translation to clinical use for cancer therapy related to issues regarding delivery, specificity or toxicity. 
     Specific strategies that target Stat3 by identifying inhibitors of Stat3 recruitment and/or dimerization have been pursued by several groups (Turkson et al., 2001; Ren et al., 2003; Shao et al., 2003; Uddin et al., 2005; Song et al., 2005; Schust et al., 2006). As outlined below, this strategy has the potential to achieve specificity based on the observation that the preferred pY peptide motif of each STAT protein is distinct. When coupled to a small molecule approach, this strategy has the potential to overcome issues of delivery and toxicity. 
     Targeting Stat3α while sparing Stat3β. Some of the distinct biochemical features of Stat3β vs. Stat3α, notably constitutive activation and a 10-to-20 fold increased DNA binding affinity, have been attributed to the absence of the C-terminal transactivation domain (TAD) resulting in increased Stat3p dimer stability (Park et al., 1996; Park et al., 2000). Increased dimer stability likely results from higher binding affinity of the SH2 domain to pY peptide motifs when in the context of Stat3p compared to Stat3α because of reduced steric hindrance conferred by removal of the TAD. These differential biochemical features between Stat3α and Stat3β are exploited to develop a chemical compound that selectively targets Stat3α, in some embodiments. This selectivity enhances the anti-tumor effect of such compounds, in certain cases, because they would spare Stat3β, which functions to antagonize the oncogenic functions of Stat3α. 
     In certain embodiments of the invention, specific therapies targeting Stat3 signaling are useful for treatment of allergic reaction. 
     VI. Combination Therapy 
     It is an aspect of this invention that a composition as disclosed herein is used in combination with another agent or therapy method, such as allergic reaction treatment. The composition(s) (which may or may not be a Stat3 inhibitor) may precede or follow the other agent treatment by intervals ranging from minutes to weeks, for example. In embodiments where the other agent and the composition of the invention are applied separately to an individual with anaphylaxis, such as upon delivery to an individual suspected of having anaphylaxis, known to have anaphylaxis, or at risk for having anaphylaxis, one would generally ensure that a significant period of time did not expire between the time of each delivery, such that the agent and composition of the invention would still be able to exert an advantageously combined effect on the individual. 
     For example, in such instances, it is contemplated that one may contact the individual with one, two, three, four or more modalities substantially simultaneously (i.e., within less than about a minute) with the composition of the invention. In other aspects, one or more agents may be administered within about 1 minute, about 5 minutes, about 10 minutes, about 20 minutes about 30 minutes, about 45 minutes, about 60 minutes, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours, about 24 hours, about 25 hours, about 26 hours, about 27 hours, about 28 hours, about 29 hours, about 30 hours, about 31 hours, about 32 hours, about 33 hours, about 34 hours, about 35 hours, about 36 hours, about 37 hours, about 38 hours, about 39 hours, about 40 hours, about 41 hours, about 42 hours, about 43 hours, about 44 hours, about 45 hours, about 46 hours, about 47 hours, to about 48 hours or more prior to and/or after administering the composition of the invention. In certain other embodiments, an agent may be administered within of from about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, about 14 days, about 15 days, about 16 days, about 17 days, about 18 days, about 19 days, about 20, to about 21 days prior to and/or after administering the composition of the invention, for example. In some situations, it may be desirable to extend the time period for treatment significantly, such as where several weeks (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7 or about 8 weeks or more) lapse between the respective administrations. In some situations, it may be desirable to extend the time period for treatment significantly, such as where several months (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7 or about 8 weeks or more) lapse between the respective administrations. 
     Various combinations may be employed, the composition of the invention is “A” and the secondary agent, which can be any other cancer therapeutic agent, is “B”: 
     
       
         
           
               
               
             
               
                   
                   
               
             
            
               
                   
                 A/B/A B/A/B B/B/A A/A/B A/B/B B/A/A A/B/B/B B/A/B/B 
               
               
                   
                 B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A 
               
               
                   
                 B/A/B/A B/A/A/B A/A/A/B B/A/A/A A/B/A/A A/A/B/A 
               
               
                   
                   
               
            
           
         
       
     
     Administration of the therapeutic compositions of the present invention to a patient will follow general protocols for the administration of drugs, taking into account the toxicity. It is expected that the treatment cycles would be repeated as necessary. 
     Exemplary combination therapies include antihistamines, steroids, epinephrine, and so on. 
     VII. Pharmaceutical Compositions 
     Pharmaceutical compositions of the present invention comprise an effective amount of a composition as disclosed herein dissolved or dispersed in a pharmaceutically acceptable carrier. The phrases “pharmaceutical” or “pharmacologically acceptable” refer to molecular entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal, such as, for example, a human, as appropriate. The preparation of a pharmaceutical composition that in some cases contains at least one Stat3 inhibitor of the invention, and in some cases an additional active ingredient, will be known to those of skill in the art in light of the present disclosure, as exemplified by Remington&#39;s Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, incorporated herein by reference. Moreover, for animal (e.g., human) administration, it will be understood that preparations should meet sterility, pyrogenicity, general safety and purity standards as required by FDA Office of Biological Standards. 
     As used herein. “pharmaceutically acceptable carrier” includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents), isotonic agents, absorption delaying agents, salts, preservatives, drugs, drug stabilizers, gels, binders, excipients, disintegration agents, lubricants, sweetening agents, flavoring agents, dyes, such like materials and combinations thereof, as would be known to one of ordinary skill in the art (see, for example, Remington&#39;s Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990. pp. 1289-1329, incorporated herein by reference). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in the therapeutic or pharmaceutical compositions is contemplated. 
     The composition(s) may comprise different types of carriers depending on whether it is to be administered in solid, liquid or aerosol form, and whether it needs to be sterile for such routes of administration such as injection. The present invention can be administered intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostaticaly, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, intramuscularly, intraperitoneally, subcutaneously, subconjunctival, intravesicularily, mucosally, intrapericardially, intraumbilically, intraocularally, orally, topically, locally, injection, infusion, continuous infusion, localized perfusion bathing target cells directly, via a catheter, via a lavage, in lipid compositions (e.g., liposomes), as an aerosol, or by other method or any combination of the forgoing as would be known to one of ordinary skill in the art (see, for example. Remington&#39;s Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, incorporated herein by reference). 
     The actual dosage amount of a composition of the present invention administered to an individual can be determined by physical and physiological factors such as body weight, severity of condition, the type of disease being treated, previous or concurrent therapeutic interventions, and the route of administration. The practitioner responsible for administration will, in any event, determine the concentration of active ingredient(s) in a composition and appropriate dose(s) for the individual subject. 
     In certain embodiments, pharmaceutical compositions may comprise, for example, at least about 0.1% of a composition. In other embodiments, the active compound may comprise between about 2% to about 75% of the weight of the unit, or between about 25% to about 60%, for example, and any range derivable therein. In other non-limiting examples, a dose may also comprise from about 0.1 mg/kg/body weight, 0.5 mg/kg/body weight, 1 mg/kg/body weight, about 5 mg/kg/body weight, about 10 mg/kg/body weight, about 20 mg/kg/body weight, about 30 mg/kg/body weight, about 40 mg/kg/body weight, about 50 mg/kg/body weight, about 75 mg/kg/body weight, about 100 mg/kg/body weight, about 200 mg/kg/body weight, about 350 mg/kg/body weight, about 500 mg/kg/body weight, about 750 mg/kg/body weight, to about 1000 mg/kg/body weight or more per administration, and any range derivable therein. In non-limiting examples of a derivable range from the numbers listed herein, a range of about 10 mg/kg/body weight to about 100 mg/kg/body weight, etc., can be administered, based on the numbers described above. In certain embodiments of the invention, various dosing mechanisms are contemplated. For example, the composition may be given one or more times a day, one or more times a week, or one or more times a month, and so forth. 
     In any case, the composition may comprise various antioxidants to retard oxidation of one or more component. Additionally, the prevention of the action of microorganisms can be brought about by preservatives such as various antibacterial and antifungal agents, including, but not limited to parabens (e.g., methylparabens, propylparabens), chlorobutanol, phenol, sorbic acid, thimerosal or combinations thereof. 
     The composition may be formulated in a free base, neutral or salt form. Pharmaceutically acceptable salts include the salts formed with the free carboxyl groups derived from inorganic bases such as for example, sodium, potassium, ammonium, calcium or ferric hydroxides; or such organic bases as isopropylamine, trimethylamine, histidine or procaine. 
     In embodiments where the composition is in a liquid form, a carrier can be a solvent or dispersion medium comprising, but not limited to, water, ethanol, polyol (e.g., glycerol, propylene glycol, liquid polyethylene glycol, etc.), lipids (e.g., triglycerides, vegetable oils, liposomes) and combinations thereof. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin; by the maintenance of the required particle size by dispersion in carriers such as, for example, liquid polyol or lipids; by the use of surfactants such as, for example, hydroxypropylcellulose; or combinations thereof such methods. In many cases, it will be preferable to include isotonic agents, such as, for example, sugars, sodium chloride or combinations thereof. 
     Sterile injectable solutions are prepared by incorporating the instant invention in the required amount of the appropriate solvent with various amounts of the other ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and/or the other ingredients. In the case of sterile powders for the preparation of sterile injectable solutions, suspensions or emulsion, the preferred methods of preparation are vacuum-drying or freeze-drying techniques which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered liquid medium thereof. The liquid medium should be suitably buffered if necessary and the liquid diluent first rendered isotonic prior to injection with sufficient saline or glucose. The preparation of highly concentrated compositions for direct injection is also contemplated, where the use of DMSO as solvent is envisioned to result in extremely rapid penetration, delivering high concentrations of the active agents to a small area. 
     The composition must be stable under the conditions of manufacture and storage, and preserved against the contaminating action of microorganisms, such as bacteria and fungi. It will be appreciated that endotoxin contamination should be kept minimally at a safe level, for example, less that 0.5 ng/mg protein. 
     In particular embodiments, prolonged absorption of an injectable composition can be brought about by the use in the compositions of agents delaying absorption, such as, for example, aluminum monostearate, gelatin or combinations thereof. 
     VIII. Kits of the Invention 
     Any of the compositions described herein may be comprised in a kit, and they are housed in a suitable container. The kits will thus comprise, in suitable container means, one or more compositions and, in some cases, an additional agent of the present invention. In some cases, there are one or more agents other than the composition of the disclosure that are included in the kit, such as one or more other agents for the treatment of anaphylaxis. In particular embodiments, there is an apparatus or any kind of means for the diagnosing of anaphylaxis. 
     The components of the kits may be packaged either in aqueous media or in lyophilized form. The container means of the kits will generally include at least one vial, test tube, flask, bottle, syringe or other container means, into which a component may be placed, and preferably, suitably aliquoted. Where there are more than one component in the kit, the kit also will generally contain a second, third or other additional container into which the additional components may be separately placed. However, various combinations of components may be comprised in a vial. The kits of the present invention also will typically include a means for containing the composition, additional agent, and any other reagent containers in close confinement for commercial sale. Such containers may include injection or blow molded plastic containers into which the desired vials are retained. 
     Compositions may also be formulated into a syringeable composition. In which case, the container means may itself be a syringe, pipette, and/or other such like apparatus, from which the formulation may be applied to an infected area of the body, injected into an animal, and/or even applied to and/or mixed with the other components of the kit. However, the components of the kit may be provided as dried powder(s). When reagents and/or components are provided as a dry powder, the powder can be reconstituted by the addition of a suitable solvent. It is envisioned that the solvent may also be provided in another container means. 
     EXAMPLES 
     The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered by the inventors to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention. 
     Example 1 
     Exemplary Materials and Methods 
     Virtual ligand screening. The inventors isolated the three-dimensional structure of the Stat3 SH2 domain from the core fragment structure of phosphorylated Stat3 homodimers bound to DNA (Becker el al., 1998) deposited in the RCSB Protein Data Bank (PDB) databank (PDB code 1BG1) and converted it to be an Internal Coordinate Mechanics (ICM)-compatible system by adding hydrogen atoms, modifying unusual amino acids, making charge adjustments and performing additional cleanup steps. In addition, the inventors retrieved the coordinates of the Stat1 SH2 domain from the PDB databank (PDB code 1BF5) for use in computational selectivity analysis (Chen et al., 1998). Commercial chemical databases (Chembridge, Asinex, ChemDiv. Enamine, Keyorganics and Life Chemicals) were chosen as sources of compounds for screening in silico. Selection was of the amide hydrogen of E638 within the site that binds the +3 residue (Q, C or T) within the pY-peptide ligand (Shao et al., 2006) as the central point of the binding pocket, which consisted of a cube with dimensions 16.0×16.9×13.7 angstrom. In addition to the +3 binding site, this cube contained the pY residue binding site consisting mainly of R609 and K591 (Shao et al., 2006) and a hydrophobic binding site consisting of Loop βC-βD  and Loop αB-αC . Sequence alignment and overlay of the Stat3 and Stat1 structures revealed substantial differences in sequence of these loops; lack of their superimposition indicated that this region might serve as a selectivity filter (Cohen et al., 2005). A flexible docking calculation (Totrov and Abagyan 1997) was performed in order to determine the global minimum energy score and thereby predict the optimum conformation of the compound within the pocket. A compound was selected for purchase and biochemical testing based on fulfilling the criteria of interaction analysis (CIA): 1) global minimum energy score ≤−30, 2) formation of a salt-bridge and/or H-bond network within the pY-residue binding site and 3) formation of a H-bond with or blocking access to the amide hydrogen of E638. Most, but not all, compounds also interacted with the hydrophobic binding site. 
     Stat3 SH2/pY-peptide binding assay. Stat3 binding assays were performed at 25° C. with a BIAcore 3000 biosensor using 20 mM Tris buffer pH 8 containing 2 mM mercaptoethanol and 5% DMSO as the running buffer (Kim et al., 2005). Phosphorylated and control non-phosphorylated biotinylated EGFR derived dodecapeptides based on the sequence surrounding Y1068 (Shao et al., 2004) were immobilized on a streptavidin coated sensor chip (BIAcore inc., Piscataway N.J.). The binding of Stat3 was conducted in 20 mM Tris buffer pH 8 containing 2 mM β-mercaptoethanol at a flow rate of 10 uL/min for 1-2 minute. Aliquots of Stat3 at 500 nM were premixed with compound to achieve a final concentration of 1-1.000 uM and incubated at 4° C. prior to being injected onto the sensor chip. The chip was regenerated by injecting 10 uL of 100 mM glycine at pH 1.5 after each sample injection. A control (Stat3 with DMSO but without compound) was run at the beginning and the end of each cycle (40 sample injections) to ensure that the integrity of the sensor chip was maintained throughout the cycle run. The average of the two controls was normalized to 100% and used to evaluate the effect of each compound on Stat3 binding. Responses were normalized by dividing the value at 2 min by the response obtained in the absence of compounds at 2 min and multiplying by 100. IC 50  values were determined by plotting % maximum response as a function of log concentration of compound and fitting the experimental points to a competitive binding model using a four parameter logistic equation: R=R high −(R high −R low )/(1+conc/A1){circumflex over ( )}A2, where R=percent response at inhibitor concentration, R high =percent response with no compound. R low =percent response at highest compound concentration. A2=fitting parameter (slope) and A1=IC 50  (BIAevaluation Software version 4.1). 
     Immunoblot assay. The human hepatocellular carcinoma cell line (HepG2) was grown in 6-well plates under standard conditions. Cells were pretreated with compounds (0, 1, 3, 10, 30, 100 and 300 uM) for 1 hour then stimulated under optimal conditions with either interferon gamma (IFN-γ; 30 ng/ml for 30 min) to activate Stat1 or interleukin-6 (IL-6; 30 ng/ml for 30 min) to activate Stat3 (30-31). Cultures were then harvested and proteins extracted using high-salt buffer, as described (Shao et al., 2006). Briefly, extracts were mixed with 2× sodium dodecyl sulfate (SDS) sample buffer (125 mmol/L Tris-HCL pH 6.8; 4% SDS; 20% glycerol; 10%2-mercaptoethanol) at a 1:1 ratio and heated for 5 minutes at 100° C. Proteins (20 μg) were separated by 7.5% SDS-PAGE and transferred to polyvinylidene fluoride (PVDF) membrane (Millipore, Waltham, Mass.) and immunoblotted. Prestained molecular weight markers (Biorad, Hercules, Calif.) were included in each gel. Membranes were probed serially with antibody against Stat1 pY 701  or Stat3 pY 705  followed by antibody against Stat1 or Stat3 (Transduction labs. Lexington, Ky.) then antibody against β-actin (Abcam, Cambridge, Mass.). Membranes were stripped between antibody probing using Restorer-Western Blot Stripping Buffer (Thermo Fisher Scientific Inc., Waltham, Mass.) per the manufacturer&#39;s instructions. Horseradish peroxidase-conjugated goat-anti-mouse IgG was used as the secondary antibody (Invitrogen Carlsbad, Calif.) and the membranes were developed with enhanced chemiluminescence (ECL) detection system (Amersham Life Sciences Inc.; Arlington Heights, Ill.). 
     Similarity screen. Three compounds identified in the initial virtual ligand screening (VLS)—Cpd3, Cpd30 and Cpd188—inhibited Stat3 SH2/pY-peptide binding and IL-6-mediated Stat3 phosphorylation and were chosen as reference molecules for similarity screening. A fingerprint similarity query for each reference compound was submitted to Molcart/ICM (Max Distance, 0.4). Similarity between each reference molecule and each database molecule was computed and the similarity results were ranked in decreasing order of ICM similarity score (Eckert and Bajorath 2007). The databases searched included ChemBridge, LifeChemicals, Enamine, ChemDiv, Asinex, AcbBlocks, KeyOrganics and PubChem for a total of 2.47 million compounds. All compounds identified were docked into the binding pocket of Stat3 SH2 domain in silico. Compounds that fulfilled CIA criteria were purchased and tested as described for compounds identified in the primary screen. 
     Electrophoretic Mobility Shift Assay (EMSA): EMSA was performed using the hSIE radiolabeled duplex oligonucleotide as a probe as described (Tweardy et al., 1995). Briefly, high salt extracts were prepared from HepG2 cells incubated without or with IL-6 (30 ng/ml) for 30 minutes. Protein concentration was determined by Bradford Assay and 20 ug of extract was incubated with compound (300 uM) for 60 minutes at 37° C. Bound and unbound hSIE probe was separated by polyacrylamide gel electrophoresis (4.5%). Gels were dried and autoradiographed. 
     Molecular modeling. All 3-D configurations of the Stat3 SH2 domain complexed with compounds were determined by global energy optimization that involves multiple steps: 1) location of organic molecules were adjusted as a whole in 2 Å amplitude by pseudo-Brownian random translations and rotations around the molecular center of gravity, 2) the internal variables of organic molecules were randomly changed. 3) coupled groups within the Stat3 SH2 domain side-chain torsion angles were sampled with biased probability shaking while the remaining variables of the protein were fixed, 4) local energy minimizations were performed using the Empirical Conformation Energy Program for Peptides type-3 (ECEPP3) in a vacuum (Nemethy et al., 1992) with distance-dependent dielectric constant ε=4r, surface-based solvent energy and entropic contributions from the protein side chains evaluated added and 5) conformations of the complex, which were determined by Metropolis criteria, were selected for the next conformation-scanning circle. The initial 3-dimensional configuration of the Stat1 SH2 domain in a complex with each compound was predicted and generated by superimposing, within the computational model, the 3-dimensional features of the Stat1 SH2 onto the 3-dimensional configuration of the Stat3 SH2 domain in a complex with each compound. The final computational model of Stat1 SH2 in a complex with each compound was determined by local minimization using Internal Coordinate Force Field (ICFF)-based molecular mechanics (Totrov and Abagyan 1997). The inventors computed the van der Waals energy of the complex of Stat1 or 3-SH2 bound with each compound using Lennard-Jones potential with ECEPP/3 force field (Nemethy et al., 1992). 
     Confocal and high-throughput fluorescence microscopy. Confocal and highthroughput fluorescence microscopy (HTFM) of MEF/GFP-Stat3α cells were performed as described (Huang et al., 2007). Briefly, for confocal fluorescence microscopy, cells were grown in 6-well plates containing a cover slip. For HTFM, cells were seeded into 96-well CC3 plates at a density of 5.000 cells/well using an automated plating system. Cells were cultured under standard conditions until 85-90% confluent. Cells were pretreated with compound for 1 hour at 37° C. then stimulated with IL-6 (200 ng/ml) and IL-6sR (250 ng/ml) for 30 minutes. Cells were fixed with 4% formaldehyde in PEM Buffer (80 mM Potassium PIPES, pH 6.8, 5 mM EGTA pH 7.0, 2 mM MgCl 2 ) for 30 minutes at 4° C., quenched in 1 mg/ml of NaBH4 (Sigma) in PEM buffer and counterstained for 1 min in 4,6-diamidino-2-phenylindole (DAPI; Sigma; 1 mg/ml) in PEM buffer. Cover slips were examined by confocal fluorescent microscopy. Plates were analyzed by automated HTFM using the Cell Lab IC Image Cytometer (IC100) platform and CytoshopVersion 2.1 analysis software (Beckman Coulter). Nuclear translocation is quantified by using the fraction localized in the nucleus (FLIN) measurement (Sharp et al., 2006). 
     Example 2 
     Identification by VLS of Compounds that Blocked Stat3 Binding to its Phosphopeptide Ligand and Inhibited IL-6-Mediated Phosphorylation of Stat3 
     The VLS protocol was used to evaluate a total of 920,000 drug-like compounds. Of these, 142 compounds fulfilled CIA criteria. These compounds were purchased and tested for their ability to block Stat3 binding to its phosphopeptide ligand in a surface plasmon resonance (SPR)-based binding assay and to inhibit IL-6-mediated phosphorylation of Stat3. SPR competition experiments showed that of the 142 compounds tested, 3 compounds—Cpd3, Cpd30 and Cpd188—were able to directly compete with pY-peptide for binding to Stat3 with IC 50  values of 447, 30, and 20 μM, respectively ( FIGS. 1 and 3 ; Table 4). 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 IC 50  values (μM) of 6 active compounds 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Assay 
                 Cpd3 
                 Cpd30 
                 Cpd188 
                 Cpd3-2 
                 Cpd3-7 
                 Cpd30-12 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 SPR 
                 447 1   
                 30 
                 20 
                 256 
                 137 
                 114 
               
               
                 pStat3 
                 91 
                 18 
                 73 
                 144 
                 63 
                 60 
               
               
                 HTM 
                 131  
                 77 
                 39 
                 150 
                 20 
                 &gt;300 
               
               
                   
               
               
                   1 Data presented are the mean or mean ± SD; ND = not determined. 
               
            
           
         
       
     
     In addition, each compound inhibited IL-6-mediated phosphorylation of Stat3 with IC50 values of 91, 18 and 73 μM respectively ( FIG. 2 ; Table 4). 
     Similarity screening with Cpd3, Cpd30 and Cpd188 identified 4,302 additional compounds. VLS screening was performed with each of these compounds, which identified 41 compounds that fulfilled CIA criteria; these were purchased and tested. SPR competition experiments showed that of these 41 compounds, 3 compounds—Cpd3-2, Cpd3-7 and Cpd30-12—were able to directly compete with pY-peptide for binding to Stat3 with IC 50  values of 256, 137 and 114 μM, respectively ( FIGS. 1 and 3 ; Table 4). In addition, each compound inhibited IL-6-mediated phosphorylation of Stat3 with IC50 values of 144, 63 and 60 μM, respectively ( FIG. 2 ; Table 4). 
     Example 3 
     Compound-Mediated Inhibition of Ligand-Stimulated Phosphorylation of Stat3 is Specific for Stat3 Vs. Stat1 
     While Stat3 contributes to oncogenesis, in part, through inhibition of apoptosis, Stat1 is anti-oncogenic; it mediates the apoptotic effects of interferons and contributes to tumor surveillance (Kaplan et al., 1998; Ramana et al., 2000). Consequently, compounds that target Stat3 while sparing Stat1, leaving its anti-oncogenic functions unopposed, may result in a synergistic anti-tumor effect. To assess the selectivity of the compounds for Stat3 vs. Stat1, HepG2 cells were incubated with Cpd3, Cpd30, Cpd188, Cpd3-2, Cpd3-7, and Cpd30-12 (300 μM) for 1 hour at 37° C. before IFN-γ stimulation ( FIG. 4 ). Only treatment with Cpd30-12 blocked Stat1 phosphorylation while each of the other five compounds—Cpd3, Cpd30, Cpd188, Cpd3-2 and Cpd3-7—did not. Thus, five of the six exemplary compounds identified were selective and inhibited ligand-stimulated phosphorylation of Stat3 but not Stat1. 
     Example 4 
     Sequence Analysis and Molecular Modeling of the Interaction of Each Compound with the Stat3 Vs. Stat1 SH2 Domain 
     To understand at the molecular level the basis for the selectivity of Cpds 3, 30, 188, 3-2 and 3-7 and the absence of selectivity in the case of Cpd 30-12, the amino acid sequence and available structures of the Stat1 and Stat3 SH2 domain were compared and also it was examined how each compound interacted with both. Sequence alignment revealed identity in the residues within Stat3 and Stat1 corresponding to the binding site for the pYresidue and the +3 residue ( FIG. 5A ). In addition, overlay of the Stat3 and Stat1 SH2 structures revealed that the loops that contained these binding sites were superimposed ( FIG. 5B ). In contrast, sequence alignment revealed substantial differences in the sequence of the regions of the SH2 domain corresponding to the loops forming the hydrophobic binding site ( FIG. 5A ). In addition, review of the overlay of Stat3 and Stat1 SH2 domains revealed that, in contrast to the close apposition of the two loops of Stat3 that form the hydrophobic binding site, the corresponding two loops of Stat1 are not closely apposed to form a pocket ( FIG. 5B ). 
     Review of computational models of Cpd3, Cpd30, Cpd188, Cpd3-2 and Cpd3-7 in a complex with the Stat3 SH2 domain revealed that each has significant interactions with the Stat3 SH2 domain binding pocket at all three binding sites, the pY-residue binding site, the +3 residue binding site and the hydrophobic binding site ( FIGS. 6A , B, C, D, and E). In contrast, Cpd30-12 interacts with the pY-residue binding site and blocks access to the +3 residue-binding site but does not interact with or block access to the hydrophobic binding site ( FIG. 6F ). In addition, van der Waals energies of the 5 selective compounds were much more favorable for their interaction with the loops of Stat3 forming the hydrophobic binding site than with corresponding loops of Stat1 ( FIG. 5C ). Thus, computer modeling indicated that activity of compounds against Stat3 derives from their ability to interact with the binding sites for the pY and the +3 residues within the binding pocket, while selectivity for Stat3 vs. Stat1 derives from the ability of compounds to interact with the hydrophobic binding site within the Stat3 SH2 binding pocket, which served as a selectivity filter. 
     Example 5 
     Inhibition of Nuclear Translocation of Phosphorylated Stat3 by Cpd3, Cpd30, Cpd188, Cpd3-2 and Cpd3-7 Assessed by HTFM 
     Following its phosphorylation on Y705. Stat3 undergoes a change in conformation from head-to-head dimerization mediated through its N-terminal oligomerization domain to tail-to-tail dimerization mediated by reciprocal SH2/pY705-peptide ligand interactions. This conformational change is followed by nuclear accumulation. Compounds that targeted SH2/pY-peptide ligand interactions of Stat3 would be expected to inhibit nuclear accumulation of Stat3. To determine if this was the case with the compounds herein, a nuclear translocation assay ( FIG. 7 ) was employed using murine embryonic fibroblast (MEF) cells that are deficient in endogenous Stat3 but constitutively express GFP-tagged Stat3α at endogenous levels. MEF/GFP-Stat3α (Huang el al., 2007). Preincubation of MEF/GFP-Stat3α cells with Cpd3, Cpd30, Cpd188, Cpd3-2 and Cpd3-7, but not Cpd30-12, blocked ligand-mediated nuclear translocation of GFP-Stat3α with IC 50  values of 131, 77, 39, 150 and 20 μM ( FIG. 7  and Table 4). 
     Example 6 
     Destabilization of Stat3-DNA Complexes by Cpd3 and Cpd3-7 
     Once in the nucleus. Stat3 dimers bind to specific DNA elements to activate and, in some instances, repress gene transcription. Tyrosine-phosphorylated dodecapeptides based on motifs within receptors that recruit Stat3 have previously been shown to destabilize Stat3 (Chakraborty et al., 1999; Shao et al., 2003). Compounds that bind to the phosphopeptide-binding site of Stat3 might be expected to do the same. To determine if this was the case for any of the identified compounds, extracts of IL-6-stimulated HepG2 cells were incubated in binding reactions containing radiolabeled hSIE ( FIG. 8 ) and each of the five selective compounds (300 μM). Incubation with Cpd3 or Cpd3-7 reduced the amount of hSIE shifted by half or greater. The other compounds did not have a detectable effect on the Stat3:hSIE band intensity. Thus, 2 of the 5 selective compounds destabilized Stat3:hSIE complexes. 
     Example 7 
     Exemplary Approach for Stat3 Inhibitors for Cancer Stem Cells 
     In the field of Stat3 probe development the inventors have focused on small molecule Stat3 probes (Xu et al., 2009), and several features of the small molecule program are useful, including: 1) a clearly defined mode of action of these probes: they target the Stat3 Src-homology (SH) 2 domain that is involved in 2 steps in the Stat3 activation pathway; 2) their specificity of action; and 3) the potential for using lead probes identified so far to identify probes with 2-to-3 logs greater activity based on recent and exemplary SAR analysis and medicinal chemistry considerations outlined below. 
     In specific embodiments, compound affinity is improved upon gaining a log greater affinity upon moving from 1 st  generation to 2nd generation probes using 3-D pharmacophore analysis. In addition, selectivity is improved through modeling embodiments, in particular through identification of a distinct hydrophobic binding domain in the phosphopeptide binding pocket of Stat3 SH2 vs. the Stat1 SH2 (Xu et al., 2009). 
     Identification of 1st generation Stat3 chemical probes. To develop chemical probes that selectively target Stat3, the inventors virtually screened 920,000 small drug-like compounds by docking each into the peptide-binding pocket of the Stat3 SH2 domain, which consists of three sites—the pY-residue binding site, the +3 residue-binding site and a hydrophobic binding site, which served as a selectivity filter (Xu et al., 2009). Three compounds (Cpd3, Cpd30 and Cpd188) satisfied criteria of interaction analysis, competitively inhibited recombinant Stat3 binding to its immobilized pY-peptide ligand and inhibited IL-6-mediated tyrosine phosphorylation of Stat3. These compounds were used in a similarity screen of 2.47 million compounds, which identified 3 more compounds (Cpd3-2, Cpd3-7 and Cpd30-12) with similar activities. Examinations of the 6 active compounds for the ability to inhibit IFN-T-mediated Stat1 phosphorylation revealed that all but Cpd30-12 were selective for Stat3. Molecular modeling of the SH2 domains of Stat3 and Stat1 bound to compound revealed that compound interaction with the hydrophobic binding site was the basis for selectivity. All 5 selective compounds inhibited nuclear-tocytoplasmic translocation of Stat3, while 3 of 5 compounds (Cpd3, Cpd30 and Cpd188) induced apoptosis preferentially of exemplary breast cancer cell lines with constitutive Stat3 activation. 
     Identification of 2nd generation Stat3 chemical probes. The similarity screening described above did not yield any hits using Cpd188, the most active of the 3 lead compounds, as the query compound. Consequently, the inventors repeated 2-D similarity screening using the scaffold of Cpd188 as the query structure and the Life Chemicals library, which yielded 207 hits. 3-D pharmacophore analysis was performed on these 207 compounds using Ligand Scout and the top 39 scoring compounds were purchased and tested for inhibition of Stat3 binding to its phosphopeptide ligand by SPR. All but six of these 39 compounds have measurable SPR IC50s, with 19 having IC50 values equal to or less than the parent compound and 2 (Cpd188-9 and Cpd188-15) having IC50 values one log lower. Examination of these 19 compounds has revealed a statistically significant correlation between 3-D pharmacophore scores and SPR IC50s and as well as 3-D pharmacophore score and IC50s for inhibition of ligand-mediated cytoplasmic-to-nuclear translocation. In addition, both Cpd188-9 and Cpd188-15 exhibited a log greater activity in inducing human leukemic cell line apoptosis than the parent Cpd188 ( FIG. 15 ). In addition, Cpd188-38 exhibited a 2 logs greater activity than parent Cpd188 in inhibiting cytoplasmic-to-nuclear translocation in HTFM assay, while Cpd188-15 exhibited a 1 log greater activity than parent Cpd188 in decreasing MSFE (Table 5). Furthermore, several of the second-generation 188-like compounds represent a substantial improvement over Cpd188 from a medicinal chemistry, metabolism and bioavailability standpoint. In particular. Cpd188-9 lacked both carboxyl groups, which in particular cases improves cell permeability and/or the thioether group, which is subject to oxidation. R2=0.2 P=0.013 (μM) 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Summary of Certain 2 nd  Generation 188-like Compounds 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 SPR IC 50 , 
                 HTFM IC 50 , 
                 Mammosphere 
               
               
                   
                 Compound 
                 μM*  
                 μM* 
                 ~IC 50 , μM*** 
               
               
                   
                   
               
               
                   
                 188 
                 20**  
                 32 ± 4  
                  30-100 
               
               
                   
                 188-1 
                 6 ± 2  
                 26 ± 4  
                 30 
               
               
                   
                 188-9 
                 3 ± 2  
                 47 ± 21 
                 10 
               
               
                   
                 188-10 
                 8 ± 3  
                 22 ± 19 
                 30 
               
               
                   
                   
               
               
                   
                 188-15 
                 2 ± 1  
                 49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 188-16 
                 4 ± 0  
                 9 ± 5  
                 30 
               
               
                   
                 188-17 
                 4 ± 2  
                 76 
                 30 
               
               
                   
                 188-18 
                 4 ± 1  
                 27 ± 8  
                 30 
               
               
                   
                   
               
               
                   
                 188-38 
                 19 ± 9   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 10-30 
               
               
                   
                   
               
               
                   
                 *mean ± SD 
               
               
                   
                 **Xu et al PLoS ONE 
               
               
                   
                 ***SUM159PT and HS578T cells plated (6 wells per test) without or with compound at 1, 10 or 100 μM, incubated 3 d; spheres counted on day 3. 
               
            
           
         
       
     
     Structure-activity relationship (SAR) analysis of 2nd generation Stat3 probes. All of the 39 second generation compounds described above, plus Cpd188 itself, are derivatives of N-naphth-1-yl benzenesulfamide. Upon careful analysis of their structure-activity relationships (SAR), the inventors found that most of these Cpd188-like compounds (38 out of 40: the rest of 2 are weak and will be described below in EXP ID) can be divided into three structural groups in a general trend of decreased activity, as shown in  FIG. 16 . Five compounds in Group III are actually the parents of compounds in Groups I and II. Addition of a variety of groups (the —R group highlighted in red in the general structure of Group I in  FIG. 16 ), such as a triazole-3-yl-mercapto (188-15) or a chloro (188-10) group, to the 3-position of the naphthylamine ring led to the Group I compounds, which are the most potent series of Stat3 probes. In a specific embodiment, this is the most important contributor to the inhibitory activity: a total of eight 3-substituents are found in Group I compounds, which invariably enhance the activity by several orders of magnitude. 
     Most Stat3 probes in Group II contain a 5-membered ring that combines the 3-R and 4-OR2 groups, such as a furan (188-11). However, the compounds in this group are, in average, ˜5× less active than the Group I compounds, which indicates that in certain aspects the H atom of the 4-hydroxy group (highlighted in blue in the general structure of Group I in  FIG. 16 ) is important, e.g., involved in a favorable H-bond with the protein. Lacking the ability to form the H-bond attributes to the weaker activities of Group II probes, in particular cases. These considerations underlie a medicinal chemistry approach outlined below. 
     Example 8 
     Medicinal Chemistry for Synthesis of 3 rd  Generation 188-Like Sulfamide Stat3 Probes 
     The crystal structure of Stat3 shows that the SH2 domain has a large, widely dispersed and generally shallow binding area with several valleys and hills that recognize the pY-peptide ligand ( FIG. 18 ). Structure-based molecular modeling (docking) was useful in identifying the contribution of the hydrophobic binding surface of the Stat3 SH2 domain as a selectivity filter (Xu et al., 2009). However, different docking programs gave distinct binding poses for the same probe over the binding surface with similar predicted binding affinities. The inventors therefore in particular embodiments, based on initial SAR results outlined above, use traditional medicinal chemistry to further carry out an exemplary comprehensive structure activity relationship study, to optimize the activity as well as the selectivity of this novel class of sulfamide probes of Stat3. Compound 188-15 serves as a scaffold for making the new generation compounds, as shown schematically ( FIG. 16 ). 
     In addition, chemistry for making these compounds is straightforward with a good yield, involving the reaction of a sulfonyl chloride with an aniline/amine, which can be either obtained commercially or synthesized readily. 
     For the proposed modifications described below, one can consult  FIG. 17 . EXP IA. Modification 1. Since almost all of the 2 nd  generation probes contain a phenylsulfonyl group, the first step towards activity optimization focuses on synthesizing a series of compounds that have a larger (e.g., bicyclic or tricyclic) or an alkyl sulfonyl group. The general synthetic route is shown as follows: 
     There are about 4.300 commercially available sulfonyl chlorides, among which 25, such as those shown above, are selected to make probes. Aniline 2, which is the amine component of compound 188-10 ( FIG. 16 ), one the most active probes, is readily made in a simple two step reaction from nitro compound 1. One can first make 25 (for example) compounds and test their activities in an in vitro rapid throughput SPR and in vivo HTFM assays. Based on the outcomes of structure-activity relationship study, more compounds can be designed and synthesized and tested in an iterative manner until optimization of this modification. 
     EXP IB. Modification 2. Next, one can modify the 3-substituent of the naphthylamine ring, based on either the structure of compound 188-15, for example. Prior SAR studies demonstrated this substituent is useful to the activity of this class of probes, in certain embodiments. However, a total of 8 groups at this position with a huge difference in size, from a single atom Cl to a large, bicyclic benzothiazole-2-ylmercapto group, showed similar activities. This feature indicates that in certain embodiments modifications at this position should be more focused on other properties, such as electrostatic interactions with the protein, as exemplified below. In addition, many of these groups are thioethers, which may be subjected to oxidation/degradation in vivo and lead to an unfavorable pharmacokinetic profile, in particular aspects. The central —S— atom is changed to a more metabolically stable isosteres, such as —CH 2 —, —NH—, and —O—, in certain cases. In certain aspects one can synthesize the following compounds to optimize the 3-substituent: 
     The synthesis is also started from 1, in certain cases. Regio-selective halogenation and formylation at the 3-position gives rise to two compounds, i.e., bromo- or iodo-compound 3 and aldehyde 4, which are versatile, common starting compounds for introducing a wide range of substituents at this position (e.g., those listed above). 
     Moreover, the crystal structure of Stat3 SH2 domain also provides strong evidence that more compounds with different electrostatic properties are useful for characterization. The electrostatic molecular surface of the protein shows two distinct features, as shown in  FIG. 18 . The first one is the negatively charged Glu638 surface stands out in the center. Next, of particular interest is a positively charged area, composed of Arg609 and Lys591 located in the edge of the domain, which is actually the pY (phosphorylated tyrosine) binding site of the receptor. The inventors also found that introducing a negatively charged group targeting the pY binding site leads to particularly active probes, in certain embodiments. For example, the docking study of the 3-phosphomethyl compound 5 (R=CH 2 PO 3   2− ) showed all of the phosphonate groups of the 20 docking poses are tightly clustered together and located in the pY binding site, indicating strong electrostatic and H-bond interactions with the residues Arg609 and Lys591 ( FIG. 18 ). 
     EXP IC. Modifications 3 and 4. Collectively, Modifications 3 and 4 test the effects of changing the substituents at the 4, 5, and 6-positions. The —OH at 4-position may be superior to —OR, in certain aspects. One can test whether the H atom in —OH is responsible for a better activity by synthesizing compounds 6 (acylated or alkylated 5), as schematically shown below. In addition, dehydroxy compounds 7 may also be made, starting from 3-bromonaphthyl-1-amine. 
     Regarding the general synthetic methods for modifying positions 5 and 6, one can first synthesize about a dozen of these compounds in this category and if very active compounds emerge, one can make more compounds to optimize the activity for these two positions. 
     EXP ID. Modification 5. The only two compounds not included in the SAR analysis (due to a different 4-substituent) are shown here, as well as their inhibitory activities against Stat3: 
     Despite the weak activity, masking the polar H of the sulfamide for the second compound is favorable, in certain aspects, which provides an easy route to making more potent probes. One can therefore use the following method to make a series of N-acyl or N-alkyl sulfamides 5: 
     Example 9 
     Identification of Stat3-Selective Chemical Probes from Sulfamide Compounds Synthesized in Example 11 
     Each novel sulfamide compound is tested for the ability to inhibit Stat3 binding to its phosphopeptide ligand by SPR and the ability to block IL-6-stimulated cytoplasmic-to-nuclear translocation in the HTFM assay. Probes with activity in these assays equivalent to or greater than the most active 2nd generation compounds are tested for inhibition of IL-6-stimulated Stat3 phosphorylation and lack of ability to inhibit IFN-γ-stimulated Stat1 phosphorylation as outlined below. 
     EXP IIA. Stat3/pY-peptide SPR binding inhibition assay. Stat3 pY-peptide binding assays is performed at 25° C. using a BIAcore 3000 biosensor as described (Xu et al., 2009). Briefly, phosphorylated and control nonphosphorylated biotinylated EGFR derived dodecapeptides based on the sequence surrounding Y1068 are immobilized on a streptavidin coated sensor chip (BIAcore Inc., Piscataway N.J.). The binding of Stat3 is performed in 20 mM Tris buffer pH 8 containing 2 mM β-mercaptoethanol at a flow rate of 10 uL/min for 1-2 minute. Aliquots of Stat3 at 500 nM are premixed with compound to achieve a final concentration of 1-1,000 uM and incubated at 4° C. prior to being injected onto the sensor chip. The chip is regenerated by injecting 10 uL of 100 mM glycine at pH 1.5 after each sample injection. A control (Stat3 with DMSO but without compound) is run at the beginning and the end of each cycle (40 sample injections) to ensure that the integrity of the sensor chip is maintained throughout the cycle run. The average of the two controls is normalized to 100% and used to evaluate the effect of each compound on Stat3 binding. Responses are normalized by dividing the value at 2 min by the response obtained in the absence of compounds at 2 min and multiplying by 100. IC 50  values are determined by plotting % maximum response as a function of log concentration of compound and fitting the experimental points to a competitive binding model using a four parameter logistic equation: R=R high −(R high −R low )/(1+conc/A1) A2 , where R=percent response at inhibitor concentration. R high =percent response with no compound, R low =percent response at highest compound concentration. A2=fitting parameter (slope) and A1=IC 50  (BIAevaluation Software version 4.1). 
     EXP IIB. High throughput fluorescence microscopy (HTFM), cytoplasm-to-nucleus translocation inhibition assays. HTFM of MEF/GFP-Stat3α cells is performed to assess the ability of probes to inhibit GFP-Stat3 cytoplasmic-to-nuclear translocation, as described (Xu et al., 2009), using the robotic system available as part of the John S. Dunn Gulf Coast Consortium for Chemical Genomics at the University of Texas-Houston School of Medicine. Briefly, cells are seeded into 96-well CC3 plates at a density of 5,000 cells/well and cultured under standard conditions until 85-90% confluent. Cells are pre-treated with compound for 1 hour at 37° C. then stimulated with IL-6 (100 ng/ml) and IL-6sR (150 ng/ml) for 30 minutes. Cells are fixed with 4% formaldehyde in PEM Buffer (80 mM Potassium PIPES, pH 6.8, 5 mM EGTA pH 7.0, 2 mM MgCl 2 ) for 30 minutes at 4° C., quenched in 1 mg/ml of NaBH 4  (Sigma) in PEM buffer and counterstained for 1 min in 4,6-diamidino-2-phenylindole (DAPI; Sigma; 1 mg/ml) in PEM buffer. Plates are analyzed by automated HTFM using the Cell Lab IC Image Cytometer (IC100) platform and CytoshopVersion 2.1 analysis software (Beckman Coulter). 
     Nuclear translocation is quantified by using the fraction localized in the nucleus (FLIN) measurement. FLIN values are normalized by subtracting the FLIN for unstimulated cells then dividing this difference by the maximum difference (delta, Δ) in FLIN (FLIN in cells stimulated with IL-6/sIL-6R in the absence of compound minus FLIN of unstimulated cells). This ratio is multiplied by 100 to obtain the percentage of maximum difference in FLIN and is plotted as a function of the log compound concentration. The best-fitting curve and IC 50  value are determined using 4-Parameter LogisticModel/Dose Response/XLfit 4.2, IDBS software. 
     EXP IIC. Ligand-mediated pStat3 and pStat1 inhibition assays. Newly synthesized Stat3 probes with activity equivalent to or greater than parent compound 188 in the SPR and HTFM assays will be tested for the ability to selectively inhibit ligand-mediated phosphorylation of Stat3 as described (Xu et al., 2009). Briefly, human hepatocellular carcinoma cells (HepG2) are grown in 6-well plates and pretreated with compounds (0, 0.1, 0.3, 1, 3, 10, 30, 100 IM) for 1 hour then stimulated under optimal conditions with either interleukin-6 (IL-6; 30 ng/ml for 30 min) to activate Stat3 or interferon gamma (IFN-γ; 30 ng/ml for 30 min) to activate Stat1. Cells are harvested and proteins extracted using high-salt buffer, mixed with 2× sodium dodecyl sulfate (SDS) sample buffer (125 mmol/L Tris-HCL pH 6.8; 4% SDS; 20% glycerol; 10%2-mercaptoethanol) at a 1:1 ratio then heated for 5 minutes at 100° C. Proteins (20 μg) are separated by 7.5% SDS-PAGE and transferred to polyvinylidene fluoride (PVDF) membrane (Millipore, Waltham, Mass.) and immunoblotted. Membranes are probed serially with antibody against Stat1 pY701 or Stat3 pY705 followed by antibody against Stat1 or Stat3 (Transduction labs. Lexington, Ky.) then antibody against β-actin (Abcam, Cambridge, Mass.). Membranes are stripped between antibody probings using Restore™ Western Blot Stripping Buffer (Thermo Fisher Scientific Inc., Waltham, Mass.) per the manufacturer&#39;s instructions. Horseradish peroxidase-conjugated goat-anti-mouse IgG is used as the secondary antibody (Invitrogen Carlsbad, Calif.) and the membranes are developed with enhanced chemiluminescence (ECL) detection system (Amersham Life Sciences Inc.; Arlington Heights, Ill.). Band intensities are quantified by densitometry. The value of each pStat3 band is divided by its corresponding total Stat3 band intensity; the results are normalized to the DMSO-treated control value. This value was plotted as a function of the log compound concentration. The best-fitting curve is determined using 4-Parameter Logistic Model/Dose Response/XLfit 4.2, IDBS software and was used to calculate the IC 50  value. 
     EXP IID. Molecular modeling of probe-Stat3 interactions. The results of modeling of the binding of the first generation probe to the Stat3 vs. Stat1 SH2 domains suggested that the basis for experimental selectivity of probes for Stat3 vs. Stat1 rested on the ability of the probes to have greater interaction with the hydrophobic binding site within the pY-peptide binding pocket of Stat3 compared to Stat1. Thus, the hydrophobic binding site served as a selectivity filter. To test if this remains the case for newly synthesized 3rd generation probes, one can use 2 complementary docking programs GLIDE (Schrödinger) and ICM (MolSoft) to determine the lowest energy docking configuration of each probe within the pY-peptide binding domain of Stat3 and Stat1 SH2 domain. One can review the computational models of each probe in a complex with the Stat3 vs. Stat1 SH2 domain and, in particular, compare the van der Waals energies and determine if they are equivalent for their interaction with the Stat3 SH2 domain vs. the Stat1 SH2 domain. It was this calculation that determined the selectivity of 1st generation probes for Stat3 vs. Stat1. In particular, van der Waals energy calculations implicated residues that form the hydrophobic binding site (W623, Q635, V637, Y640 and Y657) as critical for this selectivity. 
     In specific embodiments of the invention, there is identification of probes with one log or greater activity than 2 nd  generation probes in SPR, HTFM and pStat3 assays. Furthermore, in certain aspects some of the most active 3 rd  generation probes that emerge from this analysis are selective for Stat3 vs. Stat1 based on their greater interaction with the hydrophobic binding site within the Stat3 vs. Stat1 SH2 pY-peptide binding pocket. 
     Example 10 
     Exemplary Compositions of the Disclosure 
     Exemplary composition(s) of the disclosure are provided in Tables 6-11 below. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 IDNUMBER 
                 Structure 
                 Formula structure 
                 MW 
                 LogP 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 F1566-0306 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H17NO3S2 
                 407.5137 
                 5.846 
               
               
                   
               
               
                 F1566-0318  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H19NO3S2 
                 421.5408 
                 6.144 
               
               
                   
               
               
                 F1566-0330  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16ClNO3S2 
                 441.9587 
                 6.438 
               
               
                   
               
               
                 F1566-0342  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16BrNO3S2 
                 486.4097 
                 6.644 
               
               
                   
               
               
                 F1566-0366  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO3S2 
                 435.5679 
                 6.477 
               
               
                   
               
               
                 F1566-0414  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO3S2 
                 435.5679 
                 6.477  
               
               
                   
               
               
                 F1566-0438  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO3S2 
                 435.5679 
                 6.619 
               
               
                   
               
               
                 F1566-0450  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H19NO4S2 
                 437.5402 
                 5.802 
               
               
                   
               
               
                 F1566-0462  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO4S2 
                 451.5673 
                 6.143 
               
               
                   
               
               
                 F1566-0486  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H25NO3S2 
                 463.6221 
                 7.345 
               
               
                   
               
               
                 F1566-0510  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19NO3S2 
                 457.5742 
                 7.105 
               
               
                   
               
               
                 F1566-0546  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16N2O5S2  
                 452.5112 
                 5.818 
               
               
                   
               
               
                 F1566-0558  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18N2O5S2 
                 466.5383 
                 6.114 
               
               
                   
               
               
                 F1566-0618  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H15NO3S3 
                 413.5395 
                 5.359 
               
               
                   
               
               
                 F1566-1606  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O3S2 
                 458.5618 
                 6.046 
               
               
                   
               
               
                 F1566-1818  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H17NO3S2 
                 359.4691 
                 4.705 
               
               
                   
               
               
                 F1566-1832  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H19NO3S2 
                 373.4962 
                 5.147 
               
               
                   
               
               
                 F1566-1846  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H21NO3S2 
                 387.5233 
                 5.589 
               
               
                   
               
               
                 F1566-1860  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H15NO3S2 
                 345.442 
                 4.192 
               
               
                   
               
               
                 F5749-0371  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16N2O5S2 
                 452.5112 
                 5.781 
               
               
                   
               
               
                 F5749-0372  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H23NO3S2 
                 413.5615 
                 6.171 
               
               
                   
               
               
                 F5749-0373  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H23NO4S2 
                 465.5944 
                 6.468 
               
               
                   
               
               
                 F5749-0374  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18ClNO4S2 
                 471.9852  
                 6.429 
               
               
                   
               
               
                 F5749-0375  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO3S2   
                 435.5679 
                 6.438 
               
               
                   
               
               
                 F5749-0376  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H19NO5S2 
                 465.5507 
                 5.787 
               
               
                   
               
               
                 F5749-0377  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H20N2O4S2  
                 464.566 
                 5.137 
               
               
                   
               
               
                 F5749-0378  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO5S2 
                 467.5667  
                 5.54474 
               
               
                   
               
               
                 F5749-0379  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H19NO5S2 
                 465.5507 
                 5.441 
               
               
                   
               
               
                 F5749-0380  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H16N2O3S2  
                 408.5013 
                 4.613 
               
               
                   
               
               
                 F5749-0381  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H18N2O3S2 
                 374.4838 
                 3.74 
               
               
                   
               
               
                 F5749-0382  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO3S2 
                 435.5679 
                 6.477 
               
               
                   
               
               
                 F5749-0383  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16N2O5S2 
                 452.5112 
                 5.779 
               
               
                   
               
               
                 F5749-0384  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H19NO3S2 
                 421.5408 
                 5.98 
               
               
                   
               
               
                 F5749-0385  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H14ClNO3S3 
                 447.9845 
                 6.649 
               
               
                   
               
               
                 F5749-0386  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H15F2NO3S2 
                 443.4946 
                 6.187 
               
               
                   
               
               
                 F5749-0387  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H19N3O3S2  
                 425.5319 
                 4.956 
               
               
                   
               
               
                 F5749-0388  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H18N2O4S2 
                 426.5166 
                 4.99 
               
               
                   
               
               
                 F5749-0389  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H22N2O5S2  
                 470.5702 
                 3.633 
               
               
                   
               
               
                 F5749-0390  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18FNO4S2 
                 455.5306 
                 5.99 
               
               
                   
               
               
                 F5749-0391  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO4S2  
                 451.5673 
                 6.135 
               
               
                   
               
               
                 F5749-0392  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H20N2O3S2 
                 472.5889 
                 6.305 
               
               
                   
               
               
                 F5749-0393  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H19NO3S3  
                 441.5936 
                 6.497 
               
               
                   
               
               
                 F5749-0394  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H17NO3S3 
                 427.5665 
                 6.022 
               
               
                   
               
               
                 F5749-0395  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H19NO3S2  
                 433.5519 
                 6.204 
               
               
                   
               
               
                 F5749-0396  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16FNO3S2 
                 425.5041 
                 5.997 
               
               
                   
               
               
                 F5749-0397  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H19NO4S2  
                 437.5402 
                 5.839 
               
               
                   
               
               
                 F5749-0398  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16FNO3S2 
                 425.5041 
                 6.036 
               
               
                   
               
               
                 F5749-0399  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H15ClFNO3S2 
                 459.9492 
                 6.626 
               
               
                   
               
               
                 F5749-0400  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16F3NO4S2 
                 491.5115 
                 7.24476 
               
               
                   
               
               
                 F5749-0401  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18ClNO3S2 
                 455.9858 
                 6.771 
               
               
                   
               
               
                 F5749-0402  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H19NO4S2 
                 449.5513 
                 5.736 
               
               
                   
               
               
                 F5749-0403  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H19NO4S2 
                 449.5513 
                 5.699 
               
               
                   
               
               
                 F5749-0404  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18ClNO3S2 
                 455.9858 
                 6.732 
               
               
                   
               
               
                 F5749-0405  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H19NO4S2 
                 437.5402 
                 5.8 
               
               
                   
               
               
                 F5749-0406  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21NO4S2  
                 451.5673 
                 6.141 
               
               
                   
               
               
                 F5749-0407  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H15F2NO3S2 
                 443.4946 
                 6.148 
               
               
                   
               
               
                 F5749-0408  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H19NO3S2 
                 373.4962 
                 5.339 
               
               
                   
               
               
                 F5749-0409  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16F3NO3S2 
                 475.5121 
                 6.81776 
               
               
                   
               
               
                 F5749-0410  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16F3NO3S2 
                 475.5121 
                 6.78076 
               
               
                   
               
               
                 F5749-0411  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16ClNO3S2 
                 441.9587 
                 6.475 
               
               
                   
               
               
                 F5749-0412  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H17Cl2NO3S2  
                 490.4308 
                 7.398 
               
               
                   
               
               
                 F5749-0413  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H15F2NO3S2  
                 443.4946  
                 6.187 
               
               
                   
               
               
                 F5749-0414  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H23NO3S2  
                 449.595 
                 7.061 
               
               
                   
               
               
                 F5749-0415  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H23NO3S2 
                 461.6061 
                 6.933 
               
               
                   
               
               
                 F5749-0416  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H20N2O5S2  
                 504.5877 
                 4.973 
               
               
                   
               
               
                 F5749-0417  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O5S2 
                 518.6148 
                 5.415 
               
               
                   
               
               
                 F5749-0418  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H20N2O4S3 
                 484.6189 
                 5.149 
               
               
                   
               
               
                 F5749-0419  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H15N3O5S2 
                 441.4877 
                 2.891 
               
               
                   
               
               
                 F5749-0420  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O4S2  
                 476.5772 
                 5.042 
               
               
                   
               
               
                 F5749-0421  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N2O4S2 
                 462.5501 
                 4.954 
               
               
                   
               
               
                 F5749-0422  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H19N3O5S2 
                 469.5418 
                 2.955 
               
               
                   
               
               
                 F5749-0423  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H22N2O4S2 
                 490.6042 
                 5.277 
               
               
                   
               
               
                 F5749-0424  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18FNO3S2 
                 439.5312 
                 6.133 
               
               
                   
               
               
                 F5749-0425  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18FNO3S2  
                 439.5312 
                 6.17 
               
               
                   
               
               
                 F5749-0426  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H23NO4S2 
                 465.5944 
                 6.206 
               
               
                   
               
               
                 F5749-0427  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H25N3O3S2 
                 515.6578 
                 6.125 
               
               
                   
               
               
                 F5749-0428  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15N3O3S2 
                 397.4777 
                 3.986 
               
               
                   
               
               
                 F5749-0429  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H23N3O3S2  
                 501.6307 
                 5.991 
               
               
                   
               
               
                 F5749-0430  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H23NO5S2 
                 529.6384  
                 7.16174 
               
               
                   
               
               
                 F5749-0431  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H20ClNO4S2 
                 534.0569 
                 8.046 
               
               
                   
               
               
                 F5749-0432  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H23NO4S2 
                 513.639 
                 7.754 
               
               
                   
               
               
                 F5749-0433  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15ClF3NO3S2  
                 509.9571  
                 7.40776 
               
               
                   
               
               
                 F5749-0434  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21NO4S2  
                 499.6119 
                 7.456 
               
               
                   
               
               
                 F5749-0435  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16BrNO3S2 
                 486.4097 
                 6.642 
               
               
                   
               
               
                 F5749-0436  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16BrNO3S2 
                 486.4097 
                 6.681 
               
               
                   
               
               
                 F5749-0437  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H15BrFNO3S2 
                 504.4002 
                 6.832 
               
               
                   
               
               
                 F5749-0438  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15BrF3NO3S2 
                 554.4081 
                 7.61376 
               
               
                   
               
               
                 F5749-0439  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16ClNO3S2 
                 441.9587  
                 6.436 
               
               
                   
               
               
                 F5749-0440  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H17NO5S3  
                 471.5765 
                 5.046 
               
               
                   
               
               
                 F5749-0441  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16F3NO4S2 
                 491.5115 
                 7.24276 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 IDNUMBER 
                 Structure 
                 Formula structure 
                 MW 
                 LogP 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 F0808-0081 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO45 
                 469.5638 
                 7.101 
               
               
                   
               
               
                 F0808-0084 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO5S 
                 485.5632 
                 6.767 
               
               
                   
               
               
                 F0808-0085 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18BrNO4S 
                 520.4057 
                 7.268 
               
               
                   
               
               
                 F0808-0086 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO4S 
                 469.5638 
                 7.243 
               
               
                   
               
               
                 F0808-0089 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H21NO4S 
                 491.5702 
                 7.729 
               
               
                   
               
               
                 F0808-0091 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18FNO4S 
                 459.5001 
                 6.623 
               
               
                   
               
               
                 F0808-0092 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO4S 
                 469.5638 
                 7.101 
               
               
                   
               
               
                 F0808-0094 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18ClNO4S 
                 475.9547 
                 7.062 
               
               
                   
               
               
                 F1269-0222 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17NO4S2 
                 447.5354 
                 5.983 
               
               
                   
               
               
                 F1269-2003 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20N2O6S 
                 500.5343 
                 6.738 
               
               
                   
               
               
                 F1566-1138 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H20N2O4S 
                 492.5578 
                 6.67 
               
               
                   
               
               
                 F5749-0001 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H17NO4S 
                 379.4379 
                 4.816 
               
               
                   
               
               
                 F5749-0002 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18N2O6S 
                 486.5072 
                 6.405 
               
               
                   
               
               
                 F5749-0003 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H25NO4S 
                 447.5575 
                 6.795 
               
               
                   
               
               
                 F5749-0004 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H25NO5S 
                 499.5903 
                 7.092 
               
               
                   
               
               
                 F5749-0005 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20ClNO5S 
                 505.9812 
                 7.053 
               
               
                   
               
               
                 F5749-0006 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO4S 
                 469.5638 
                 7.062 
               
               
                   
               
               
                 F5749-0007 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21NO6S 
                 499.5467 
                 6.411 
               
               
                   
               
               
                 F5749-0008 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H22N2O5S 
                 498.5619 
                 5.761 
               
               
                   
               
               
                 F5749-0009 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO6S 
                 501.5626 
                 6.16874 
               
               
                   
               
               
                 F5749-0010 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21NO6S 
                 499.5467 
                 6.065 
               
               
                   
               
               
                 F5749-0011 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O4S 
                 442.4972 
                 5.237 
               
               
                   
               
               
                 F5749-0012 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H19NO4S 
                 393.465 
                 5.329 
               
               
                   
               
               
                 F5749-0013 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO6S 
                 501.5626 
                 6.417 
               
               
                   
               
               
                 F5749-0014 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H20N2O4S 
                 408.4797 
                 4.364 
               
               
                   
               
               
                 F5749-0015 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO4S 
                 469.5638 
                 7.101 
               
               
                   
               
               
                 F5749-0016 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18N2O6S 
                 486.5072 
                 6.403 
               
               
                   
               
               
                 F5749-0017 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H21NO4S 
                 407.4921 
                 5.771 
               
               
                   
               
               
                 F5749-0018 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H21NO4S 
                 455.5367 
                 6.604 
               
               
                   
               
               
                 F5749-0019 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H23NO4S 
                 421.5192 
                 6.213 
               
               
                   
               
               
                 F5749-0020 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H16ClNO4S2 
                 481.9804 
                 7.273 
               
               
                   
               
               
                 F5749-0021 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17F2NO4S 
                 477.4905 
                 6.811 
               
               
                   
               
               
                 F5749-0022 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H21N3O4S 
                 459.5278 
                 5.58 
               
               
                   
               
               
                 F5749-0023 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O5S 
                 460.5126 
                 5.614 
               
               
                   
               
               
                 F5749-0024 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H24N2O6S 
                 504.5661 
                 4.257 
               
               
                   
               
               
                 F5749-0025 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20FNO5S 
                 489.5266 
                 6.614 
               
               
                   
               
               
                 F5749-0026 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO5S 
                 485.5632 
                 6.759 
               
               
                   
               
               
                 F5749-0027 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H22N2O4S 
                 506.5848 
                 6.929 
               
               
                   
               
               
                 F5749-0028 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H21NO4S2 
                 475.5896 
                 7.121 
               
               
                   
               
               
                 F5749-0029 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H19NO4S2 
                 461.5625 
                 6.646 
               
               
                   
               
               
                 F5749-0030 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21NO4S 
                 467.5479 
                 6.828 
               
               
                   
               
               
                 F5749-0031 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18FNO4S 
                 459.5001 
                 6.621 
               
               
                   
               
               
                 F5749-0032 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H21NO5S 
                 471.5361 
                 6.463 
               
               
                   
               
               
                 F5749-0033 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18FNO4S 
                 459.5001 
                 6.66 
               
               
                   
               
               
                 F5749-0034 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17ClFNO4S 
                 493.9451 
                 7.25 
               
               
                   
               
               
                 F5749-0035 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H18F3NO5S 
                 525.5074 
                 7.86876 
               
               
                   
               
               
                 F5749-0036 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20ClNO4S 
                 489.9818 
                 7.395 
               
               
                   
               
               
                 F5749-0037 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21NO5S 
                 483.5473 
                 6.36 
               
               
                   
               
               
                 F5749-0038 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21NO5S 
                 483.5473 
                 6.323 
               
               
                   
               
               
                 F5749-0039 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20ClNO4S 
                 489.9813 
                 7.356 
               
               
                   
               
               
                 F5749-0040 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H21NO5S 
                 471.5361 
                 6.424 
               
               
                   
               
               
                 F5749-0041 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H23NO5S 
                 485.5632 
                 6.765 
               
               
                   
               
               
                 F5749-0042 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17F2NO4S 
                 477.4905 
                 6.772 
               
               
                   
               
               
                 F5749-0043 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H21NO4S 
                 407.4921 
                 5.963 
               
               
                   
               
               
                 F5749-0044 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H18F3NO4S 
                 509.508 
                 7.44176 
               
               
                   
               
               
                 F5749-0045 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H18F3NO4S 
                 509.508 
                 7.40476 
               
               
                   
               
               
                 F5749-0046 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18ClNO4S 
                 475.9547 
                 7.099 
               
               
                   
               
               
                 F5749-0047 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H19Cl2NO4S 
                 524.4268 
                 8.022 
               
               
                   
               
               
                 F5749-0048 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17F2NO4S 
                 477.4905 
                 6.811 
               
               
                   
               
               
                 F5749-0049 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H25NO4S 
                 483.5909 
                 7.685 
               
               
                   
               
               
                 F5749-0050 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H25NO4S 
                 495.6021 
                 7.557 
               
               
                   
               
               
                 F5749-0051 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H22N2O6S 
                 538.5836 
                 5.597 
               
               
                   
               
               
                 F5749-0052 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C31H24N2O6S 
                 552.6107 
                 6.039 
               
               
                   
               
               
                 F5749-0053 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O5S2 
                 518.6148 
                 5.773 
               
               
                   
               
               
                 F5749-0054 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17N3O6S 
                 475.4836 
                 3.515 
               
               
                   
               
               
                 F5749-0055 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H22N2O5S 
                 510.5731 
                 5.666 
               
               
                   
               
               
                 F5749-0056 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H20N2O5S 
                 496.546 
                 5.578 
               
               
                   
               
               
                 F5749-0057 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H21N3O6S 
                 503.5378 
                 3.579 
               
               
                   
               
               
                 F5749-0058 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H24N2O5S 
                 524.6002 
                 5.901 
               
               
                   
               
               
                 F5749-0059 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20FNO4S 
                 473.5272 
                 6.757 
               
               
                   
               
               
                 F5749-0060 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20FNO4S 
                 473.5272 
                 6.794 
               
               
                   
               
               
                 F5749-0061 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H25NO5S 
                 499.5903 
                 6.83 
               
               
                   
               
               
                 F5749-0062 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C32H27N3O4S 
                 549.6537 
                 6.749 
               
               
                   
               
               
                 F5749-0063 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H17N3O4S 
                 431.4736 
                 4.61 
               
               
                   
               
               
                 F5749-0064 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C31H25N3O4S 
                 535.6266 
                 6.615 
               
               
                   
               
               
                 F5749-0065 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C33H25NO6S 
                 563.6343 
                 7.78574 
               
               
                   
               
               
                 F5749-0066 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C32H22ClNO5S 
                 568.0528 
                 8.67 
               
               
                   
               
               
                 F5749-0067 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C33H25NO5S 
                 547.6349 
                 8.378 
               
               
                   
               
               
                 F5749-0068 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H17ClF3NO4S 
                 543.953 
                 8.03176 
               
               
                   
               
               
                 F5749-0069 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C32H23NO5S 
                 533.6078 
                 8.08 
               
               
                   
               
               
                 F5749-0070 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18BrNO4S 
                 520.4057 
                 7.266 
               
               
                   
               
               
                 F5749-0071 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18BrNO4S 
                 520.4057 
                 7.305 
               
               
                   
               
               
                 F5749-0072 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17BrFNO4S 
                 538.3961 
                 7.456 
               
               
                   
               
               
                 F5749-0073 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H17BrF3NO4S 
                 588.404 
                 8.23776 
               
               
                   
               
               
                 F5749-0074 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18ClNO4S 
                 475.9547 
                 7.06 
               
               
                   
               
               
                 F5749-0075 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19NO6S2 
                 505.5724 
                 5.67 
               
               
                   
               
               
                 F5749-0076 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H18F3NO5S 
                 525.5074 
                 7.86676 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 8 
               
               
                   
               
               
                 IDNUMBER 
                 Structure 
                 Formula structure 
                 MW 
                 LogP 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 F1566-0329 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H20N2O3S2 
                 472.5889 
                 6.344 
               
               
                   
               
               
                 F1566-0341 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17ClN2O3S2 
                 493.0068 
                 6.638 
               
               
                   
               
               
                 F1566-0353 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17BrN2O3S2 
                 537.4578 
                 6.844 
               
               
                   
               
               
                 F1566-0377 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O3S2 
                 486.616 
                 6.677 
               
               
                   
               
               
                 F1566-0425 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O3S2 
                 486.616 
                 6.677 
               
               
                   
               
               
                 F1566-0449 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O3S2 
                 486.616 
                 6.819 
               
               
                   
               
               
                 F1566-0473 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O4S2 
                 502.6154 
                 6.343 
               
               
                   
               
               
                 F1566-0497 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H26N2O3S2 
                 514.6702 
                 7.545 
               
               
                   
               
               
                 F1566-0521 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H20N2O3S2 
                 508.6224 
                 7.305 
               
               
                   
               
               
                 F1566-0557 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17N3O5S2 
                 503.5593 
                 6.018 
               
               
                   
               
               
                 F1566-0569 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19N3O5S2 
                 517.5864 
                 6.314 
               
               
                   
               
               
                 F1566-0617 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O5S2 
                 518.6148 
                 5.993 
               
               
                   
               
               
                 F1566-0629 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16N2O3S3 
                 464.5876 
                 5.559 
               
               
                   
               
               
                 F1566-1608 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H19N3O3S2 
                 509.6099 
                 6.246 
               
               
                   
               
               
                 F1566-1821 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H18N2O3S2 
                 410.5172 
                 4.905 
               
               
                   
               
               
                 F1566-1835 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H20N2O3S2 
                 424.5443 
                 5.347 
               
               
                   
               
               
                 F1566-1849 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H22N2O3S2 
                 438.5714 
                 5.789 
               
               
                   
               
               
                 F1566-1863 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H16N2O3S2 
                 396.4901 
                 4.392 
               
               
                   
               
               
                 F5749-0077 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17N3O5S2 
                 503.5593 
                 5.981 
               
               
                   
               
               
                 F5749-0078 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H24N2O3S2 
                 464.6096 
                 6.371 
               
               
                   
               
               
                 F5749-0079 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H24N2O4S2 
                 516.6425 
                 6.668 
               
               
                   
               
               
                 F5749-0080 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19ClN2O4S2 
                 523.0333 
                 6.629 
               
               
                   
               
               
                 F5749-0081 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O3S2 
                 486.616 
                 6.638 
               
               
                   
               
               
                 F5749-0082 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20N2O5S2 
                 516.5989 
                 5.987 
               
               
                   
               
               
                 F5749-0083 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H21N3O4S2 
                 515.6141 
                 5.337 
               
               
                   
               
               
                 F5749-0084 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O5S2 
                 518.6148 
                 5.74474 
               
               
                   
               
               
                 F5749-0085 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20N2O5S2 
                 516.5989 
                 5.641 
               
               
                   
               
               
                 F5749-0086 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17N3O3S2 
                 459.5494 
                 4.813 
               
               
                   
               
               
                 F5749-0087 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H19N3O3S2 
                 425.5319 
                 3.94 
               
               
                   
               
               
                 F5749-0088 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O3S2 
                 486.616 
                 6.677 
               
               
                   
               
               
                 F5749-0089 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17N3O5S2 
                 503.5593 
                 5.979 
               
               
                   
               
               
                 F5749-0090 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H20N2O3S2 
                 472.5889 
                 6.18 
               
               
                   
               
               
                 F5749-0091 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15ClN2O3S3 
                 499.0326 
                 6.849 
               
               
                   
               
               
                 F5749-0092 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H16F2N2O3S2 
                 494.5427 
                 6.387 
               
               
                   
               
               
                 F5749-0093 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H20N403S2 
                 476.58 
                 5.156 
               
               
                   
               
               
                 F5749-0094 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H19N3O4S2 
                 477.5647 
                 5.19 
               
               
                   
               
               
                 F5749-0095 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H23N3O5S2 
                 521.6183 
                 3.833 
               
               
                   
               
               
                 F5749-0096 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19FN2O4S2 
                 506.5787 
                 6.19 
               
               
                   
               
               
                 F5749-0097 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O4S2 
                 502.6154 
                 6.335 
               
               
                   
               
               
                 F5749-0098 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H216N3O3S2 
                 523.637 
                 6.505 
               
               
                   
               
               
                 F5749-0099 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O3S3 
                 492.6418 
                 6.697 
               
               
                   
               
               
                 F5749-0100 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N2O3S3 
                 478.6147 
                 6.222 
               
               
                   
               
               
                 F5749-0101 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20N2O3S2 
                 484.6001 
                 6.404 
               
               
                   
               
               
                 F5749-0102 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17FN2O3S2 
                 476.5522 
                 6.197 
               
               
                   
               
               
                 F5749-0103 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H20N2O4S2 
                 488.5883 
                 6.039 
               
               
                   
               
               
                 F5749-0104 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17FN2O3S2 
                 476.5522 
                 6.236 
               
               
                   
               
               
                 F5749-0105 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H16ClFN2O3S2 
                 510.9973 
                 6.826 
               
               
                   
               
               
                 F5749-0106 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17F3N2O4S2 
                 542.5596 
                 7.44476 
               
               
                   
               
               
                 F5749-0107 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19ClN2O3S2 
                 507.0339 
                 6.971 
               
               
                   
               
               
                 F5749-0108 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20N2O4S2 
                 500.5995 
                 5.936 
               
               
                   
               
               
                 F5749-0109 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H20N2O4S2 
                 500.5995 
                 5.899 
               
               
                   
               
               
                 F5749-0110 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19ClN2O3S2 
                 507.0339 
                 6.932 
               
               
                   
               
               
                 F5749-0111 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H20N2O4S2 
                 488.5883 
                 6 
               
               
                   
               
               
                 F5749-0112 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O4S2 
                 502.6154 
                 6.341 
               
               
                   
               
               
                 F5749-0113 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H16F2N2O3S2 
                 494.5427 
                 6.348 
               
               
                   
               
               
                 F5749-0114 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H20N2O3S2 
                 424.5443 
                 5.539 
               
               
                   
               
               
                 F5749-0115 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17F3N2O3S2 
                 526.5602 
                 7.01776 
               
               
                   
               
               
                 F5749-0116 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17F3N2O3S2 
                 526.5602 
                 6.98076 
               
               
                   
               
               
                 F5749-0117 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17ClN2O3S2 
                 493.0068 
                 6.675 
               
               
                   
               
               
                 F5749-0118 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H18Cl2N2O3S2 
                 541.479 
                 7.598 
               
               
                   
               
               
                 F5749-0119 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H16F2N2O3S2 
                 494.5427 
                 6.387 
               
               
                   
               
               
                 F5749-0120 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H24N2O3S2 
                 500.6431 
                 7.261 
               
               
                   
               
               
                 F5749-0121 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H24N2O3S2 
                 512.6542 
                 7.133 
               
               
                   
               
               
                 F5749-0122 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H21N3O5S2 
                 555.6358 
                 5.173 
               
               
                   
               
               
                 F5749-0123 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H23N3O5S2 
                 569.6629 
                 5.615 
               
               
                   
               
               
                 F5749-0124 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H21N3O4S3 
                 535.667 
                 5.349 
               
               
                   
               
               
                 F5749-0125 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16N4O5S2 
                 492.5358 
                 3.091 
               
               
                   
               
               
                 F5749-0126 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21N3O4S2 
                 527.6253 
                 5.242 
               
               
                   
               
               
                 F5749-0127 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H19N3O4S2 
                 513.5982 
                 5.154 
               
               
                   
               
               
                 F5749-0128 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N4O5S2 
                 520.59 
                 3.155 
               
               
                   
               
               
                 F5749-0129 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H23N3O4S2 
                 541.6524 
                 5.477 
               
               
                   
               
               
                 F5749-0130 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19FN2O3S2 
                 490.5793 
                 6.333 
               
               
                   
               
               
                 F5749-0131 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19FN2O3S2 
                 490.5793 
                 6.37 
               
               
                   
               
               
                 F5749-0132 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H24N2O4S2 
                 516.6425 
                 6.406 
               
               
                   
               
               
                 F5749-0133 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C31H26N4O3S2 
                 566.7059 
                 6.325 
               
               
                   
               
               
                 F5749-0134 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16N4O3S2 
                 448.5258 
                 4.186 
               
               
                   
               
               
                 F5749-0135 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H24N4O3S2 
                 552.6788 
                 6.191 
               
               
                   
               
               
                 F5749-0136 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C32H24N2O5S2 
                 580.6865 
                 7.36174 
               
               
                   
               
               
                 F5749-0137 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C31H21ClN2O4S2 
                 585.105 
                 8.246 
               
               
                   
               
               
                 F5749-0138 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C32H24N2O4S2 
                 564.6871 
                 7.954 
               
               
                   
               
               
                 F5749-0139 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H16ClF3N2O3S2 
                 561.0052 
                 7.60776 
               
               
                   
               
               
                 F5749-0140 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C31H22N2O4S2 
                 550.66 
                 7.656 
               
               
                   
               
               
                 F5749-0141 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17BrN2O3S2 
                 537.4578 
                 6.842 
               
               
                   
               
               
                 F5749-0142 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17BrN2O3S2 
                 537.4578 
                 6.881 
               
               
                   
               
               
                 F5749-0143 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H16BrFN2O3S2 
                 555.4483 
                 7.032 
               
               
                   
               
               
                 F5749-0144 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H16BrF3N2O3S2 
                 605.4562 
                 7.81376 
               
               
                   
               
               
                 F5749-0145 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17ClN2O3S2 
                 493.0068 
                 6.636 
               
               
                   
               
               
                 F5749-0146 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O5S3 
                 522.6246 
                 5.246 
               
               
                   
               
               
                 F5749-0147 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17F3N2O4S2 
                 542.5596 
                 7.44276 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 IDNUMBER 
                 Structure 
                 Formula structure 
                 MW 
                 LogP 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 F1565-0253 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14N4O3S2 
                 398.4653 
                 3.698 
               
               
                   
               
               
                 F1566-0328 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H16N4O3S2 
                 412.4924 
                 3.996 
               
               
                   
               
               
                 F1566-0340 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13ClN4O3S2 
                 432.9103 
                 4.29 
               
               
                   
               
               
                 F1566-0520 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16N4O3S2 
                 448.5258 
                 4.957 
               
               
                   
               
               
                 F1566-0556 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13N5O5S2 
                 443.4628 
                 3.67 
               
               
                   
               
               
                 F1566-0568 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15N5O5S2 
                 457.4899 
                 3.966 
               
               
                   
               
               
                 F1566-0616 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N4O5S2 
                 458.5183 
                 3.645 
               
               
                   
               
               
                 F1566-0628 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H12N4O3S3 
                 404.491 
                 3.211 
               
               
                   
               
               
                 F1566-0148 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C13H12N4O3S2 
                 336.3936 
                 2.044 
               
               
                   
               
               
                 F5749-0149 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13N5O5S2 
                 443.4628 
                 3.633 
               
               
                   
               
               
                 F5749-0150 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H20N4O3S2 
                 404.5131 
                 4.023 
               
               
                   
               
               
                 F5749-0151 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H20N4O4S2 
                 456.546 
                 4.32 
               
               
                   
               
               
                 F5749-0152 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15ClN4O4S2 
                 462.9368 
                 4.281 
               
               
                   
               
               
                 F5749-0153 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N4O3S2 
                 426.5195 
                 4.29 
               
               
                   
               
               
                 F5749-0154 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H16N4O5S2 
                 456.5023 
                 3.639 
               
               
                   
               
               
                 F5749-0155 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H17N5O4S2 
                 455.5176 
                 2.989 
               
               
                   
               
               
                 F5749-0156 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N4O5S2 
                 458.5183 
                 3.39674 
               
               
                   
               
               
                 F5749-0157 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H16N4O5S2 
                 456.5023 
                 3.293 
               
               
                   
               
               
                 F5749-0158 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13N5O3S2 
                 399.4529 
                 2.465 
               
               
                   
               
               
                 F5749-0159 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C14H14N4O3S2 
                 350.4207 
                 2.557 
               
               
                   
               
               
                 F5749-0160 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C14H15N5O3S2 
                 365.4354 
                 1.592 
               
               
                   
               
               
                 F5749-0161 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N4O3S2 
                 426.5195 
                 4.329 
               
               
                   
               
               
                 F5749-0162 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13N5O5S2 
                 443.4628 
                 3.631 
               
               
                   
               
               
                 F5749-0163 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C15H16N4O3S2 
                 364.4478 
                 2.999 
               
               
                   
               
               
                 F5749-0164 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H16N4O3S2 
                 412.4924 
                 3.832 
               
               
                   
               
               
                 F5749-0165 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H18N4O3S2 
                 378.4749 
                 3.441 
               
               
                   
               
               
                 F5749-0166 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11ClN4O3S3 
                 438.9361 
                 4.501 
               
               
                   
               
               
                 F5749-0167 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H12F2N4O3S2 
                 434.4461 
                 4.039 
               
               
                   
               
               
                 F5749-0168 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H16N6O3S2 
                 416.4835 
                 2.808 
               
               
                   
               
               
                 F5749-0169 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H15N5O4S2 
                 417.4682 
                 2.842 
               
               
                   
               
               
                 F5749-0170 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H19N5O5S2 
                 461.5218 
                 1.485 
               
               
                   
               
               
                 F5749-0171 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15FN4O4S2 
                 446.4822 
                 3.842 
               
               
                   
               
               
                 F5749-0172 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N4O4S2 
                 442.5189 
                 3.987 
               
               
                   
               
               
                 F5749-0173 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H17N5O3S2 
                 463.5405 
                 4.157 
               
               
                   
               
               
                 F5749-0174 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H15N5O3S2 
                 449.5134 
                 3.898 
               
               
                   
               
               
                 F5749-0175 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16N4O3S3 
                 432.5452 
                 4.349 
               
               
                   
               
               
                 F5749-0176 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H14N4O3S3 
                 418.5181 
                 3.874 
               
               
                   
               
               
                 F5749-0177 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H16N4O3S2 
                 424.5035 
                 4.056 
               
               
                   
               
               
                 F5749-0178 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13FN4O3S2 
                 416.4557 
                 3.849 
               
               
                   
               
               
                 F5749-0179 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H16N4O4S2 
                 428.4918 
                 3.691 
               
               
                   
               
               
                 F5749-0180 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13FN4O3S2 
                 416.4557 
                 3.888 
               
               
                   
               
               
                 F5749-0181 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H12ClFN4O3S2 
                 450.9007 
                 4.478 
               
               
                   
               
               
                 F5749-0182 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H13F3N4O4S2 
                 482.4631 
                 5.09676 
               
               
                   
               
               
                 F5749-0183 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15ClN4O3S2 
                 446.9374 
                 4.623 
               
               
                   
               
               
                 F5749-0184 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H16N4O4S2 
                 440.5029 
                 3.588 
               
               
                   
               
               
                 F5749-0185 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H16N4O4S2 
                 440.5029 
                 3.551 
               
               
                   
               
               
                 F5749-0186 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15ClN4O3S2 
                 446.9374 
                 4.584 
               
               
                   
               
               
                 F5749-0187 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H16N4O4S2 
                 428.4918 
                 3.652 
               
               
                   
               
               
                 F5749-0188 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N4O4S2 
                 442.5189 
                 3.993 
               
               
                   
               
               
                 F5749-0189 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H12F2N4O3S2 
                 434.4461 
                 4 
               
               
                   
               
               
                 F5749-0190 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C15H16N4O3S2 
                 364.4478 
                 3.191 
               
               
                   
               
               
                 F5749-0191 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H13F3N4O3S2 
                 466.4637 
                 4.66976 
               
               
                   
               
               
                 F5749-0192 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H13F3N4O3S2 
                 466.4637 
                 4.63276 
               
               
                   
               
               
                 F5749-0193 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13ClN4O3S2 
                 432.9103 
                 4.327 
               
               
                   
               
               
                 F5749-0194 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H14Cl2N4O3S2 
                 481.3824 
                 5.25 
               
               
                   
               
               
                 F5749-0195 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H12F2N4O3S2 
                 434.4461 
                 4.039 
               
               
                   
               
               
                 F5749-0196 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H20N4O3S2 
                 440.5466 
                 4.913 
               
               
                   
               
               
                 F5749-0197 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H20N4O3S2 
                 452.5577 
                 4.785 
               
               
                   
               
               
                 F5749-0198 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H17N5O5S2 
                 495.5393 
                 2.825 
               
               
                   
               
               
                 F5749-0199 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H19N5O5S2 
                 509.5664 
                 3.267 
               
               
                   
               
               
                 F5749-0200 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H17N5O4S3 
                 475.5704 
                 3.001 
               
               
                   
               
               
                 F5749-0201 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H12N6O5S2 
                 432.4392 
                 0.743 
               
               
                   
               
               
                 F5749-0202 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H17N5O4S2 
                 467.5287 
                 2.894 
               
               
                   
               
               
                 F5749-0203 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H15N5O4S2 
                 453.5017 
                 2.806 
               
               
                   
               
               
                 F5749-0204 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16N6O5S2 
                 460.4934 
                 0.807 
               
               
                   
               
               
                 F5749-0205 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H19N5O4S2 
                 481.5558 
                 3.129 
               
               
                   
               
               
                 F5749-0206 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15FN4O3S2 
                 430.4828 
                 3.985 
               
               
                   
               
               
                 F5749-0207 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15FN4O3S2 
                 430.4828 
                 4.022 
               
               
                   
               
               
                 F5749-0208 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H20N4O4S2 
                 456.546 
                 4.058 
               
               
                   
               
               
                 F5749-0209 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H22N6O3S2 
                 506.6093 
                 3.977 
               
               
                   
               
               
                 F5749-0210 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C15H12N6O3S2 
                 388.4293 
                 1.838 
               
               
                   
               
               
                 F5749-0211 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H20N6O3S2 
                 492.5823 
                 3.843 
               
               
                   
               
               
                 F5749-0212 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N4O5S2 
                 520.59 
                 5.01374 
               
               
                   
               
               
                 F5749-0213 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17ClN4O4S2 
                 525.0085 
                 5.898 
               
               
                   
               
               
                 F5749-0214 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N4O4S2 
                 504.5906 
                 5.606 
               
               
                   
               
               
                 F5749-0215 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H12ClF3N4O3S2 
                 500.9087 
                 5.25976 
               
               
                   
               
               
                 F5749-0216 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N4O4S2 
                 490.5635 
                 5.308 
               
               
                   
               
               
                 F5749-0217 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13BrN4O3S2 
                 477.3613 
                 4.494 
               
               
                   
               
               
                 F5749-0218 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13BrN4O3S2 
                 477.3613 
                 4.533 
               
               
                   
               
               
                 F5749-0219 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H12BrFN4O3S2 
                 495.3517 
                 4.684 
               
               
                   
               
               
                 F5749-0220 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H12BrFN4O3S2 
                 545.3597 
                 5.46576 
               
               
                   
               
               
                 F5749-0221 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13ClN4O3S2 
                 432.9103 
                 4.288 
               
               
                   
               
               
                 F5749-0222 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14N4O5S3 
                 462.5281 
                 2.898 
               
               
                   
               
               
                 F5749-0223 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H13F3N4O4S2 
                 482.4631 
                 5.09476 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 IDNUMBER 
                 Structure 
                 Formula structure 
                 MW 
                 LogP 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 F0808-0128 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O3S3 
                 492.6418 
                 6.892 
               
               
                   
               
               
                 F0808-0132 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16N2O3S3 
                 464.5876 
                 6.261 
               
               
                   
               
               
                 F0808-0133 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15ClN2O3S3 
                 499.0326 
                 6.853 
               
               
                   
               
               
                 F0808-0134 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N2O3S3 
                 478.6147 
                 6.559 
               
               
                   
               
               
                 F0808-0136 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O3S3 
                 492.6418 
                 7.034 
               
               
                   
               
               
                 F0808-0137 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15BrN2O3S3 
                 543.4836 
                 7.059 
               
               
                   
               
               
                 F1269-0225 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H14N2O3S4 
                 470.6133 
                 5.774 
               
               
                   
               
               
                 F1269-1420 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N2O4S3 
                 494.6141 
                 6.217 
               
               
                   
               
               
                 F1566-1144 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H17N3O3S3 
                 515.6357 
                 6.461 
               
               
                   
               
               
                 F1566-1584 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17N3O5S3 
                 523.6122 
                 6.529 
               
               
                   
               
               
                 F1566-1596 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O5S3 
                 524.6406 
                 6.208 
               
               
                   
               
               
                 F1566-1816 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H16N2O3S3 
                 416.543 
                 5.12 
               
               
                   
               
               
                 F1566-1830 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N2O3S3 
                 430.5701 
                 5.562 
               
               
                   
               
               
                 F1566-1844 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H20N2O3S3 
                 444.5972 
                 6.004 
               
               
                   
               
               
                 F1566-1858 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14N2O3S3 
                 402.5159 
                 4.607 
               
               
                   
               
               
                 F5749-0224 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15N3O5S3 
                 509.5851 
                 6.196 
               
               
                   
               
               
                 F5749-0225 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H22N2O3S3 
                 470.6354 
                 6.586 
               
               
                   
               
               
                 F5749-0226 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H22N2O4S3 
                 522.6682 
                 6.883 
               
               
                   
               
               
                 F5749-0227 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17ClN2O4S3 
                 529.0591 
                 6.844 
               
               
                   
               
               
                 F5749-0228 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O3S3 
                 492.6418 
                 6.853 
               
               
                   
               
               
                 F5749-0229 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O5S3 
                 522.6246 
                 6.202 
               
               
                   
               
               
                 F5749-0230 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H19N3O4S3 
                 521.6399 
                 5.552 
               
               
                   
               
               
                 F5749-0231 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O5S3 
                 524.6406 
                 5.95974 
               
               
                   
               
               
                 F5749-0232 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O5S3 
                 522.6246 
                 5.856 
               
               
                   
               
               
                 F5749-0233 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H15N3O3S3 
                 465.5752 
                 5.028 
               
               
                   
               
               
                 F5749-0234 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H17N3O3S3 
                 431.5576 
                 4.155 
               
               
                   
               
               
                 F5749-0235 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O3S3 
                 492.6418 
                 6.892 
               
               
                   
               
               
                 F5749-0236 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15N3O5S3 
                 509.5851 
                 6.194 
               
               
                   
               
               
                 F5749-0237 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N2O3S3 
                 478.6147 
                 6.395 
               
               
                   
               
               
                 F5749-0238 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H13ClN2O3S4 
                 505.0584 
                 7.064 
               
               
                   
               
               
                 F5749-0239 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H14F2N2O3S3 
                 500.5684 
                 6.602 
               
               
                   
               
               
                 F5749-0240 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H18N4O3S3 
                 482.6058 
                 5.371 
               
               
                   
               
               
                 F5749-0241 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H17N3O4S3 
                 483.5905 
                 5.405 
               
               
                   
               
               
                 F5749-0242 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H21N3O5S3 
                 527.6441 
                 4.048 
               
               
                   
               
               
                 F5749-0243 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17FN2O4S3 
                 512.6045 
                 6.405 
               
               
                   
               
               
                 F5749-0244 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O4S3 
                 508.6412 
                 6.55 
               
               
                   
               
               
                 F5749-0245 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H19N3O3S3 
                 529.6628 
                 6.72 
               
               
                   
               
               
                 F5749-0246 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18N2O3S4 
                 498.6675 
                 6.912 
               
               
                   
               
               
                 F5749-0247 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16N2O3S4 
                 484.6404 
                 6.437 
               
               
                   
               
               
                 F5749-0248 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O3S3 
                 490.6258 
                 6.619 
               
               
                   
               
               
                 F5749-0249 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15FN2O3S3 
                 482.578 
                 6.412 
               
               
                   
               
               
                 F5749-0250 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N2O4S3 
                 494.6141 
                 6.254 
               
               
                   
               
               
                 F5749-0251 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15FN2O3S3 
                 482.578 
                 6.451 
               
               
                   
               
               
                 F5749-0252 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H14ClFN2O3S3 
                 517.023 
                 7.041 
               
               
                   
               
               
                 F5749-0253 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H15F3N2O4S3 
                 548.5854 
                 7.65976 
               
               
                   
               
               
                 F5749-0254 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17ClN2O3S3 
                 513.0597 
                 7.186 
               
               
                   
               
               
                 F5749-0255 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O4S3 
                 506.6252 
                 6.151 
               
               
                   
               
               
                 F5749-0256 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H18N2O4S3 
                 506.6252 
                 6.114 
               
               
                   
               
               
                 F5749-0257 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17ClN2O3S3 
                 513.0597 
                 7.147 
               
               
                   
               
               
                 F5749-0258 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H18N2O4S3 
                 494.6141 
                 6.215 
               
               
                   
               
               
                 F5749-0259 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H20N2O4S3 
                 508.6412 
                 6.556 
               
               
                   
               
               
                 F5749-0260 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H14F2N2O3S3 
                 500.5684 
                 6.563 
               
               
                   
               
               
                 F5749-0261 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18N2O3S3 
                 430.5701 
                 5.754 
               
               
                   
               
               
                 F5749-0262 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H15F3N2O3S3 
                 532.586 
                 7.23276 
               
               
                   
               
               
                 F5749-0263 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H15F3N2O3S3 
                 532.586 
                 7.19576 
               
               
                   
               
               
                 F5749-0264 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15ClN2O3S3 
                 499.0326 
                 6.89 
               
               
                   
               
               
                 F5749-0265 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H16Cl2N2O3S3 
                 547.5047 
                 7.813 
               
               
                   
               
               
                 F5749-0266 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H14F2N2O3S3 
                 500.5684 
                 6.602 
               
               
                   
               
               
                 F5749-0267 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H22N2O3S3 
                 506.6688 
                 7.476 
               
               
                   
               
               
                 F5749-0268 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H22N2O3S3 
                 518.68 
                 7.348 
               
               
                   
               
               
                 F5749-0269 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H19N3O5S3 
                 561.6616 
                 5.388 
               
               
                   
               
               
                 F5749-0270 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H21N3O5S3 
                 575.6887 
                 5.83 
               
               
                   
               
               
                 F5749-0271 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H19N3O4S4 
                 541.6927 
                 5.564 
               
               
                   
               
               
                 F5749-0272 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H14N4O5S3 
                 498.5615 
                 3.306 
               
               
                   
               
               
                 F5749-0273 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H19N3O4S3 
                 533.651 
                 5.457 
               
               
                   
               
               
                 F5749-0274 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C25H17N3O4S3 
                 519.6239 
                 5.369 
               
               
                   
               
               
                 F5749-0275 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18N4O5S3 
                 526.6157 
                 3.37 
               
               
                   
               
               
                 F5749-0276 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C27H21N3O4S3 
                 547.6781 
                 5.692 
               
               
                   
               
               
                 F5749-0277 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17FN2O3S3 
                 496.6051 
                 6.548 
               
               
                   
               
               
                 F5749-0278 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H17FN2O3S3 
                 496.6051 
                 6.585 
               
               
                   
               
               
                 F5749-0279 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C26H22N2O4S3 
                 522.6682 
                 6.621 
               
               
                   
               
               
                 F5749-0280 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H24N4O3S3 
                 572.7316 
                 6.54 
               
               
                   
               
               
                 F5749-0281 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H14N4O3S3 
                 454.5516 
                 4.401 
               
               
                   
               
               
                 F5749-0282 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C28H22N4O3S3 
                 558.7045 
                 6.406 
               
               
                   
               
               
                 F5749-0283 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H22N2O5S3 
                 586.7122 
                 7.57674 
               
               
                   
               
               
                 F5749-0284 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H19ClN2O4S3 
                 591.1308 
                 8.461 
               
               
                   
               
               
                 F5749-0285 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C30H22N2O4S3 
                 570.7128 
                 8.169 
               
               
                   
               
               
                 F5749-0286 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H14ClF3N2O3S3 
                 567.031 
                 7.82276 
               
               
                   
               
               
                 F5749-0287 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C29H20N2O4S3 
                 556.6858 
                 7.871 
               
               
                   
               
               
                 F5749-0288 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15BrN2O3S3 
                 543.4836 
                 7.057 
               
               
                   
               
               
                 F5749-0289 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15BrN2O3S3 
                 543.4836 
                 7.096 
               
               
                   
               
               
                 F5749-0290 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H14BrFN2O3S3 
                 561.474 
                 7.247 
               
               
                   
               
               
                 F5749-0291 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H14BrF3N2O3S3 
                 611.482 
                 8.02876 
               
               
                   
               
               
                 F5749-0292 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H15ClN2O3S3 
                 499.0326 
                 6.851 
               
               
                   
               
               
                 F5749-0293 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H16N2O5S4 
                 528.6504 
                 5.461 
               
               
                   
               
               
                 F5749-0294 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C24H15F3N2O4S3 
                 548.5854 
                 7.65776 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 11 
               
               
                   
               
               
                 ID NUMBER 
                 Structure 
                 Formula structure 
                 MW 
                 LogP 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 F0433-0038 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H12ClNO3S 
                 333.7959 
                 4.192 
               
               
                   
               
               
                 F0433-0041 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H14ClNO3S 
                 347.823 
                 4.49 
               
               
                   
               
               
                 F0433-0044 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11Cl2NO3S 
                 368.241 
                 4.784 
               
               
                   
               
               
                 F0433-0047 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H14ClNO4S 
                 363.8224 
                 4.148 
               
               
                   
               
               
                 F0433-0050 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H14ClNO3S 
                 383.8565 
                 5.451 
               
               
                   
               
               
                 F0808-1895 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO3S 
                 361.8501 
                 4.823 
               
               
                   
               
               
                 F0808-1902 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11BrClNO3S 
                 412.692 
                 4.99 
               
               
                   
               
               
                 F0808-1909 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11ClN2O5S 
                 378.7935 
                 4.164 
               
               
                   
               
               
                 F0808-1913 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO3S 
                 361.8501 
                 4.823 
               
               
                   
               
               
                 F0808-1914 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H20ClNO3S 
                 389.9043 
                 5.691 
               
               
                   
               
               
                 F1269-0272 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C14H10ClNO3S2 
                 339.8217 
                 3.705 
               
               
                   
               
               
                 F1269-1995 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13ClN2O5S 
                 392.8206 
                 4.46 
               
               
                   
               
               
                 F1566-1223 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H13ClN2O3S 
                 384.8441 
                 4.392 
               
               
                   
               
               
                 F5749-0295 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C11H10ClNO3S 
                 271.7243 
                 2.538 
               
               
                   
               
               
                 F5749-0296 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11ClN2O5S 
                 378.7935 
                 4.127 
               
               
                   
               
               
                 F5749-0297 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H18ClNO3S 
                 339.8438 
                 4.517 
               
               
                   
               
               
                 F5749-0298 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H18ClNO4S 
                 391.8766 
                 4.814 
               
               
                   
               
               
                 F5749-0299 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13Cl2NO4S 
                 398.2675 
                 4.775 
               
               
                   
               
               
                 F5479-0300 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO3S 
                 361.8501 
                 4.784 
               
               
                   
               
               
                 F5749-0301 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14ClNO5S 
                 391.833 
                 4.133 
               
               
                   
               
               
                 F5749-0302 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H15ClN2O4S 
                 390.8483 
                 3.483 
               
               
                   
               
               
                 F5749-0303 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO5S 
                 393.8489 
                 3.89074 
               
               
                   
               
               
                 F5749-0304 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14ClNO5S 
                 391.833 
                 3.787 
               
               
                   
               
               
                 F5749-0305 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C15H11ClN2O3S 
                 334.7835 
                 2.959 
               
               
                   
               
               
                 F5749-0306 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C12H12ClNO3S 
                 285.7513 
                 3.051 
               
               
                   
               
               
                 F5749-0307 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO5S 
                 393.8489 
                 4.139 
               
               
                   
               
               
                 F5749-0308 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C12H13ClN2O3S 
                 300.766 
                 2.086 
               
               
                   
               
               
                 F5749-0309 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO3S 
                 361.8501 
                 4.823 
               
               
                   
               
               
                 F5749-0310 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11ClN2O5S 
                 378.7935 
                 4.125 
               
               
                   
               
               
                 F5749-0311 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C13H14ClNO3S 
                 299.7784 
                 3.493 
               
               
                   
               
               
                 F5749-0312 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H14ClNO3S 
                 347.823 
                 4.326 
               
               
                   
               
               
                 F5749-0313 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C14H16ClNO3S 
                 313.8055 
                 3.935 
               
               
                   
               
               
                 F5749-0314 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C14H9Cl2NO3S2 
                 374.2667 
                 4.995 
               
               
                   
               
               
                 F5749-0315 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H10ClF2NO3S 
                 369.7768 
                 4.533 
               
               
                   
               
               
                 F5749-0316 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C15H14ClN3O3S 
                 351.8141 
                 3.302 
               
               
                   
               
               
                 F5749-0317 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C15H13ClN2O4S 
                 352.7989 
                 3.336 
               
               
                   
               
               
                 F5749-0318 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H17ClN2O5S 
                 396.8524 
                 1.979 
               
               
                   
               
               
                 F5749-0319 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13ClFNO4S 
                 381.8129 
                 4.336 
               
               
                   
               
               
                 F5749-0320 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO4S 
                 377.8495 
                 4.481 
               
               
                   
               
               
                 F5749-0321 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H15ClN2O3S 
                 398.8712 
                 4.651 
               
               
                   
               
               
                 F5749-0322 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H14ClNO3S2 
                 367.8759 
                 4.843 
               
               
                   
               
               
                 F5749-0323 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C15H12ClNO3S2 
                 353.8488 
                 4.368 
               
               
                   
               
               
                 F5749-0324 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14ClNO3S 
                 359.8342 
                 4.55 
               
               
                   
               
               
                 F5749-0325 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11ClFNO3S 
                 351.7864 
                 4.343 
               
               
                   
               
               
                 F5749-0326 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H14ClNO4S 
                 363.8224 
                 4.185 
               
               
                   
               
               
                 F5749-0327 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11ClFNO3S 
                 351.7864 
                 4.382 
               
               
                   
               
               
                 F5749-0328 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H10Cl2FNO3S 
                 386.2314 
                 4.972 
               
               
                   
               
               
                 F5749-0329 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H11ClF3NO4S 
                 417.7937 
                 5.59076 
               
               
                   
               
               
                 F5749-0330 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13Cl2NO3S 
                 382.2681 
                 5.117 
               
               
                   
               
               
                 F5749-0331 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14ClNO4S 
                 375.8336 
                 4.082 
               
               
                   
               
               
                 F5749-0332 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H14ClNO4S 
                 375.8336 
                 4.045 
               
               
                   
               
               
                 F5749-0333 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13Cl2NO3S 
                 382.2681 
                 5.078 
               
               
                   
               
               
                 F5749-0334 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H14ClNO4S 
                 363.8224 
                 4.146 
               
               
                   
               
               
                 F5749-0335 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H16ClNO4S 
                 377.8495 
                 4.487 
               
               
                   
               
               
                 F5749-0336 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H10ClF2NO3S 
                 369.7768 
                 4.494 
               
               
                   
               
               
                 F5749-0337 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C13H14ClNO3S 
                 299.7784 
                 3.685 
               
               
                   
               
               
                 F5749-0338 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H11ClF3NO3S 
                 401.7943 
                 5.16376 
               
               
                   
               
               
                 F5749-0339 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H11ClF3NO3S 
                 401.7943 
                 5.12676 
               
               
                   
               
               
                 F5749-0340 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11Cl2NO3S 
                 368.241 
                 4.821 
               
               
                   
               
               
                 F5749-0341 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H12Cl3NO3S 
                 416.7131 
                 5.744 
               
               
                   
               
               
                 F5749-0342 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H10ClF2NO3S 
                 369.7768 
                 4.533 
               
               
                   
               
               
                 F5749-0343 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H18ClNO3S 
                 375.8772 
                 5.407 
               
               
                   
               
               
                 F5749-0344 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H18ClNO3S 
                 387.8884 
                 5.279 
               
               
                   
               
               
                 F5749-0345 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H15ClN2O5S 
                 430.87 
                 3.319 
               
               
                   
               
               
                 F5749-0346 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H17ClN2O5S 
                 444.897 
                 3.761 
               
               
                   
               
               
                 F5749-0347 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H15ClN2O4S2 
                 410.9011 
                 3.495 
               
               
                   
               
               
                 F5749-0348 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C14H10ClN3O5S 
                 367.7699 
                 1.237 
               
               
                   
               
               
                 F5749-0349 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H15ClN2O4S 
                 402.8594 
                 3.388 
               
               
                   
               
               
                 F5749-0350 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C18H13ClN2O4S 
                 388.8323 
                 3.3 
               
               
                   
               
               
                 F5749-0351 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H14ClN3O5S 
                 395.8241 
                 1.301 
               
               
                   
               
               
                 F5749-0352 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C20H17ClN2O4S 
                 416.8865 
                 3.623 
               
               
                   
               
               
                 F5749-0353 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13ClFNO3S 
                 365.8135 
                 4.479 
               
               
                   
               
               
                 F5749-0354 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H13ClFNO3S 
                 365.8135 
                 4.516 
               
               
                   
               
               
                 F5749-0355 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C19H18ClNO4S 
                 391.8766 
                 4.552 
               
               
                   
               
               
                 F5749-0356 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H20ClN3O3S 
                 441.94 
                 4.471 
               
               
                   
               
               
                 F5749-0357 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C13H10ClN3O3S 
                 323.76 
                 2.332 
               
               
                   
               
               
                 F5749-0358 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C21H18ClN3O3S 
                 427.9129 
                 4.337 
               
               
                   
               
               
                 F5749-0359 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18ClNO5S 
                 455.9206 
                 5.50774 
               
               
                   
               
               
                 F5749-0360 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H15Cl2NO4S 
                 460.3392 
                 6.392 
               
               
                   
               
               
                 F5749-0361 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C23H18ClNO4S 
                 439.9212 
                 6.1 
               
               
                   
               
               
                 F5749-0362 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H10Cl2F3NO3S 
                 436.2394 
                 5.75376 
               
               
                   
               
               
                 F5749-0363 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C22H16ClNO4S 
                 425.8941 
                 5.802 
               
               
                   
               
               
                 F5749-0364 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11BrClNO3S 
                 412.692 
                 4.988 
               
               
                   
               
               
                 F5749-0365 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11BrClNO3S 
                 412.692 
                 5.027 
               
               
                   
               
               
                 F5749-0366 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H10BrClFNO3S 
                 430.6824 
                 5.178 
               
               
                   
               
               
                 F5749-0367 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H10BrClF3NO3S 
                 480.6904 
                 5.95976 
               
               
                   
               
               
                 F5749-0368 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H11Cl2NO3S 
                 368.241 
                 4.782 
               
               
                   
               
               
                 F5749-0369 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C16H12ClNO5S2 
                 397.8587 
                 3.392 
               
               
                   
               
               
                 F5749-0370 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 C17H11ClF3NO4S 
                 417.7937 
                 5.58876 
               
               
                   
               
            
           
         
       
     
     Example 11 
     A Role for Stat3 Signaling in Mast Cell Degranulation 
     Autosomal-dominant hyper-IgE syndrome (AD-HIES) patients carry dominant-negative STAT3 mutations, develop frequent skin and lung infections, and also have a variety of non-immunologic manifestations affecting bones and connective tissue. In addition, almost all have an eczematous rash present very early in life, as well as the markedly elevated serum IgE levels which give the disease its name. Of note, one-third of patients in the broader population with atopic dermatitis develop food allergies. Despite these observations, the susceptibility of AD-HIES patients to specific food allergies has not been carefully examined. The inventors have found that fewer AD-HIES patients develop food allergies and anaphylaxis than patients with marked IgE elevations and eczema without STAT3 mutations. In embodiments of the invention, this is due at least in part to the effects of defective STAT3 signaling on mast cell degranulation. 
     Thirty eight percent of STAT3-mutant patients had immediate hypersensitivity to food, significantly less than the 58.3% observed in atopic patients without a STAT3 mutation ( FIG. 19A ). Far fewer AD-HIES patients had anaphylaxis to a food allergen than atopic controls (8.5% vs. 33.3%) ( FIG. 19B ). 
     Furthermore, silencing of STAT3 expression inhibited mast cell degranulation following IgE crosslinking in direct proportion to the degree of silencing of STAT3 in LAD2 cells ( FIG. 21 ). Similarly, silencing of STAT3 in primary human mast cells lead to decreased IgE-mediated mast cell degranulation ( FIG. 20B ). 
     Example 12 
     Examples of Compositions for Anaphylaxis Treatment 
     One or more compositions are characterized as anaphylaxis treatment and/or prevention using standard means in the art. In certain cases, a rodent model of anaphylaxis is employed to test one or more compositions of interest for effectiveness in anaphylaxis. In at least some aspects, a temperature drop in the rodent is used as a measure of anaphylaxis. 
     Systemic Anaphylaxis Assay 
     Any suitable in vivo model of anaphylaxis may be employed. Mice may be sensitized (i.v., for example) with an effective amount of DNP-specific IgE (H1-DNP-e -26 ) in an appropriate buffer and challenged (i.v., for example) after an appropriate amount of time (24 h, for example) with an effective amount of rat anti-mouse IgE. 
     Alternatively, anaphylaxis may be induced by injection (i.v.) of compound 48/80 (Sigma Aldrich) at a sub-lethal concentration (for example, concentrations less than 100 μg in 200 μl of buffer were lethal). Implantable electronic transponders (Bio Medic Data Systems) may be inserted under the dorsal skin of anesthetized mice at least 24 hrs before the start of the anaphylaxis studies. Basal body temperatures before induction of anaphylaxis and temperature changes during anaphylaxis may be monitored using an electronic scanner (Bio Medic Data Systems). 
     Therapeutic Assay 
     In certain embodiments, the composition being tested (for example, Cpd 188-9) is provided to the individual for a period of at least 1, 2, 3, 4, 5, 6, 7, or more days; the administration may be by any suitable route, including intravenous, subcutaneous, aerosolization, inhalation, orally, and so forth. Following this period of time, anaphylaxis may be induced in the model system. 
       FIG. 22  demonstrates effective treatment in an anaphylaxis model using Cpd188-9. Mice as an anaphylaxis model were pre-treated with 50 mg/kg Cpd 188-9 or which vehicle for one week, after which anaphylaxis was induced via systemic IgE cross-linking at time 0. Detectably within at least 40 minutes the reverse in temperature drop occurred, demonstrating effective use in anaphylaxis conditions. 
       FIG. 23  illustrates dose response using different examples of dosages of Cpd188-9 on normal human mast cells in vitro. Beta-hexosaminidase (% release) is used as an example of a measure of mast cell degranulation, which reflects the intensity of anaphylaxis. With increasing amounts of Cpd 188-9 administered for at least three days prior, mast cell degranulation was reduced. 
       FIG. 24  shows that systemic anaphylaxis was prevented in vivo with an exemplary STAT3 inhibitor. Healthy wild-type mice were pretreated for either one day (top panel) or one week (bottom panel) with C188-9 at 50 mg/kg. Mice were then injected with IgE specific for an antigen, and the following day the antigen was injected and drop in body temperature recorded as a measure of anaphylaxis. Inhibition of the drop is shown only in the bottom panel, when mice were pretreated (in red) for one week with C188-9. 
       FIG. 25  demonstrates that peripheral and central vascular leakage is decreased by Cpd 188-9. Mice were pretreated with C188-9 for one week as in  FIG. 24 , then injected with a dye to measure the inhibition by C188-9 of locally induced IgE-mediated vascular leakage (top left) or mast cell secretagogue C48/80-induced vascular leakage (top right) or platelet activating factor-induced drop in hematocrit—a measure of vascular leakage (bottom). 
       FIG. 26  illustrates that the effect of Cpd188-9 is not because of a decreased mast cell degranulation in vivo. Serum histamine and MCPT-1 levels are shown at 90 seconds (left panels) or 30 minutes (right panels) after Ag-challenge after 1 week C188-9 treatment as in  FIG. 24 . There was no statistical difference, suggesting that mast cell degranulation was not a factor in C188-9 mediated inhibition in mice. 
       FIG. 27  demonstrates the effect of Cpd 188-9 on Ag-induced degranulation in murine mast cells. Pretreatment of murine bone marrow derived mast cells or peritoneal derived mast cells with C188-9 does not lead to inhibition of mast cell degranulation, in contrast to human mast cells as in  FIG. 23 . Only incubation of mouse peritoneal mast cells with IL-6 (left panel) enables mast cells to be mildly inhibited by C188-9. 
       FIG. 28  shows a schematic representation of transwell permeability assay to measure vascular endothelial cell permeability in response to soluble factors and inhibitors. 
       FIG. 29  demonstrates inhibition of vascular permeability of human umbilical vein endothelial cells (HUVECs) by C188-9 pretreated for one week+/−IL-6. DMSO was used as a control for C188-9. Transwell assay was performed in response to 100 um of histamine. Maximal inhibition was seen with 1 ug C188-9 (on right). 
       FIG. 30  shows that Hyper-IgE syndrome mouse is resistant to anaphylaxis (Siegel et al., JACI, 2013). Systemic anaphylaxis is induced as in  FIG. 24  in a mouse model of the Hyper-IgE syndrome. Mice with dominant negative STAT3 mutations were less prone to severe temperature drop with IgE crosslinking than littermate controls. 
       FIG. 31  demonstrates STAT3 mutant (HIES6) HUVECS resistant to histamine-induced permeability. Human umbilical vein endothelial cells derived from patients with dominant negative STAT3 mutations (HIES6) were less responsive to histamine induced vascular permeability than healthy controls (labeled HUVECS). This is direct evidence that impaired STAT3 signaling leads to impaired vascular permeability responses to histamine. 
     Thus, Cpd188-9 pretreatment of 7 days (but under at least some conditions not one) inhibits systemic anaphylaxis in vivo. In specific embodiments, the action is more in vascular endothelial responses to STAT3 than in mast cells, whereas human mast cell and endothelial responses are both highly affected. 
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