lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cnc2c(N)c(C(=O)NCCc3ccc(N4CC5CCC(C4)N5)c(Cl)c3)sc2n1
InChIKey: LQMMGNMDUZEDGU-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: Each assay was performed in a final volume of 20 μL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2) (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.01% Prionex (0.22 μM filtered, Sigma # G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at −20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at −20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 μM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin-Rhodamine 110, R&D Systems # U-555) concentration was 25 nM with [Ub-Rh110]<<Km. 10 μL of 2× enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2×Ub-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 μL of 2×Ub-Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 457, ALogP 3.15, HBA 7, HBD 3, PSA 96.17, QED 0.55
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(OCc3c(Cl)cccc3OC(F)(F)F)ccc12
InChIKey: RGAGCZDCRLIULM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: In Vitro Functional Activity (Agonism) on Human S1P5 Receptors: The CHO-human-S1P5-Aeqorin assay was bought from Euroscreen, Brussels (Euroscreen, Technical dossier, Human Lysophospholid S1P5 (Edg8) receptor, DNA clone and CHO AequoScreen™ recombinant cell-line, catalog no: ES-593-A, September 2006). Human-S1P5-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P5 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 3 independent experiments were performed in single point's measurements.
Measurement: EC50 = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 485.89, ALogP 5.02, HBA 5, HBD 1, PSA 68.23, QED 0.59
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCN2CCCC(C)C2)cc1
InChIKey: CUKJWVHEMLBESD-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 = 1228 nM (pChEMBL 5.909999847412109)
Descriptors: MW 317.52, ALogP 5.27, HBA 2, HBD 0, PSA 12.47, QED 0.61
Compound (SMILES): O=C1c2ccccc2C(=O)c2c1nnn2-c1ccccc1
InChIKey: KXGSYSDSQRXROA-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin) assessed as reduction in L-kynurenine formation using L-tryptophan as substrate incubated for 30 mins by microplate spectrophotometry analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 275.27, ALogP 2.04, HBA 5, HBD 0, PSA 64.85, QED 0.53
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCCN2CCCCC2)cc1
InChIKey: NVODSBDSTGAOMT-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 345.57, ALogP 6.19, HBA 2, HBD 0, PSA 12.47, QED 0.44
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCCN2CCCCCC2)cc1
InChIKey: VYNGDPLRECMOSF-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 = 1495 nM (pChEMBL 5.829999923706055)
Descriptors: MW 359.6, ALogP 6.58, HBA 2, HBD 0, PSA 12.47, QED 0.41
Compound (SMILES): Nc1nc2oc3ccc(C4CCNCC4)cc3c(=O)c2cc1C(=O)O
InChIKey: UWBCIUTVTKTYST-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Kinase Assays: Kinase assays are commonly used for determining the ability of a small molecule to inhibit enzyme activity. By measuring the degree of phosphorylation of a substrate at varying concentrations of inhibitor, the concentration of inhibitor resulting in 50% enzymatic activity (IC50) can be obtained. The IC50 is defined as the inflection point of the sigmoidal graph obtained when plotting substrate phosphorylation vs. inhibitor concentration. Experiments were conducted during development of embodiments herein using radiolabeled ATP to detect substrate phosphorylation in the presence of amlexanox analogs to determine the potency (IC50) of said analogs.TBK1 (residues 1-657) and IKKε (residues 1-655) were purified from insect cells to ≥90% purity by coomassie staining. Reactions containing 50 nM TBK1 or IKKε, 7 μM myelin basic protein (MBP), and inhibitor in reaction buffer (50 mM HEPES pH 7.5, 10 mM NaCl, 10 mM MgCl2, 1 mM DTT) were initiated with 5 μM ATP spiked with [γ-32P]-ATP and allowed to proceed for 30 minutes at room temperature. Reactions were quenched with SDS gel loading dye, run on 4-15% SDS-PAGE gels, and imaged on phosphorimaging screens. Band intensities corresponding to phosphorylated MBP were quantified with ImageQuant and the data analyzed in Prism 6. Dose-response assay band intensities were normalized and fit to a sigmoidal dose-response equation with the Hill slope fixed at −1 and the top constrained to 100.
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 339.35, ALogP 2.09, HBA 6, HBD 3, PSA 118.45, QED 0.61
Compound (SMILES): NCc1ccc(Oc2ccc(S(=O)(=O)CC3CS3)cc2)cc1
InChIKey: GRRDUDJQILRRES-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Enzyme Inhibition Assay: Human recombinant active MMP-2 and MMP-7, and the catalytic domains of MMP-3 and MMP-14/MT1-MMP were purchased from EMD Chemicals, Inc. (San Diego, Calif., USA); human recombinant catalytic domains of MMP-1, MMP-8, and MMP-9 were purchased from Enzo Life Sciences, Inc. (Farmingdale, N.Y., USA); human recombinant active ADAM9 and ADAM10 were purchased from R&D Systems (Minneapolis, Minn., USA). Fluorogenic substrates MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 (for MMP-2, MMP-7, MMP-9 and MMP-14) and MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 (for MMP-3) were purchased from Peptides International (Louisville, Ky., USA); Mca-KPLGL-Dpa-AR-NH2 (for MMP-1, MMP-8 and ADAM10) and Mca-PLAQAV-Dpa-RSSSR-NH2 (for ADAM9) were purchased from R&D Systems (Minneapolis, Minn., USA). The Km values for MMP-2, MMP-9 and MMP-14 were the same as previously reported by Gooyit et al. ((2013) J. Med. Chem. 56(20):8139-8150). Inhibitor stock solutions (10 mM) were prepared freshly in DMSO before enzyme inhibition assays. We followed the same methodology for enzyme inhibition studies as reported before by Page-McCaw et al. ((2007) Nat Rev Mol Cell Biol 8(3):221-233). Enzyme inhibition studies were carried out using a Cary Eclipse fluorescence spectrophotometer (Varian, Walnut Creek, Calif., USA). Compound 1 was stable in the buffers used in the kinetic assays.
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 335.45, ALogP 2.83, HBA 5, HBD 1, PSA 69.39, QED 0.82
Compound (SMILES): NCCc1ccc(-c2cccc(F)c2)cc1
InChIKey: QQIZQBKKQAFAJV-UHFFFAOYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at Gs-mediated TAAR1 activation (unknown origin) expressed in HEK293 cells pretreated with coelenterazine for 30 mins followed by compound addition by BRET assay
Measurement: EC50 = 1.17 nM (pChEMBL 8.930000305175781)
Descriptors: MW 215.27, ALogP 2.99, HBA 1, HBD 1, PSA 26.02, QED 0.84
Compound (SMILES): O=S(=O)(NCCN1CCNCC1)c1ccc(NC2CCCCC2)c(NCc2ccccc2)c1
InChIKey: HSYSVXKJIVUNBR-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid lipoxygenase ALOX15 (SINGLE PROTEIN), Homo sapiens
UniProt: P16050
Assay: Inhibition of 15-LOX (unknown origin)
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 471.67, ALogP 3.23, HBA 6, HBD 4, PSA 85.5, QED 0.43
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCCCN2CCCCCC2)cc1
InChIKey: OCDZXKYOYHCDPQ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 373.63, ALogP 6.97, HBA 2, HBD 0, PSA 12.47, QED 0.37
Compound (SMILES): CC(C)(O)c1cccn2c(C3(c4ccc(Cl)cc4)CC3)nnc12
InChIKey: PTIFVLOBVCIMKL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 327.82, ALogP 3.69, HBA 4, HBD 1, PSA 50.42, QED 0.8
Compound (SMILES): C[C@@H]1CCCN1Cc1cc(C(=O)Nc2ccc3c(c2)N(C)C(=O)CC3)ccc1-c1ccccc1
InChIKey: UVEZHZVGDONTIH-HXUWFJFHSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human TRPV1 expressed in HEK293 cells assessed as inhibition of resiniferatoxin-induced increase in intracellular Ca2+ level
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 453.59, ALogP 5.5, HBA 3, HBD 1, PSA 52.65, QED 0.56
Compound (SMILES): c1ccc([C@@H]2C[C@H]2NC2CCNCC2)cc1
InChIKey: BASFYRLYJAZPPL-UONOGXRCSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant LSD1 (unknown origin) (catalytic domain 157 to 852 residues) expressed in Escherichia coli BL21 using H3K4me1 as substrate incubated for 1 hr by horse-radish peroxidase/amplex red-based fluorescence method
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 216.33, ALogP 1.88, HBA 2, HBD 2, PSA 24.06, QED 0.81
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(C#Cc3ccccc3)ccc12
InChIKey: OWHUUJZBNSHXSC-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: In Vitro Functional Activity (Agonism) on Human S1P5 Receptors: The CHO-human-S1P5-Aeqorin assay was bought from Euroscreen, Brussels (Euroscreen, Technical dossier, Human Lysophospholid S1P5 (Edg8) receptor, DNA clone and CHO AequoScreen™ recombinant cell-line, catalog no: ES-593-A, September 2006). Human-S1P5-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P5 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 3 independent experiments were performed in single point's measurements.
Measurement: EC50 = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 361.44, ALogP 3.29, HBA 3, HBD 1, PSA 49.77, QED 0.85
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCN2CCC(C)CC2)cc1
InChIKey: QHLCQRLEFPCFJI-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 331.54, ALogP 5.66, HBA 2, HBD 0, PSA 12.47, QED 0.54
Compound (SMILES): COc1cc(-c2nn(C)cc2-c2ccncc2)ccc1C#Cc1cccc(C)n1
InChIKey: VMLCBKKFIWPXDQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: In Vitro Enzymatic Assay: The PDE enzymatic reaction was carried out in assay buffer (20 mM Tris-HCl pH7.5, 10 mM MgCl2, 0.1% bovine serum albumin) containing enzyme and substrate. The PDE enzymes concentration ranged from 10 pM-250 pM, depending on each enzyme's specific activity. The substrate cyclic nucleotide (cAMP or cGMP) concentration used in the assay was 20 nM for PDE10, and 100 nM for other PDEs. The inhibitory effect of compound was determined by incubating various concentration of inhibitor in the enzymatic assay. Typically, compound was serial diluted in DMSO then further diluted in assay buffer. Next, the compound at varying concentration was mixed with PDE enzyme. The reaction was initiated by addition of cyclic nucleotide substrate, and incubated for 60 minutes at 29 C. The reaction was stopped by addition of lysis buffer from assay kit. The cAMP-d2 and anti-cAMP cryptate in the lysis buffer detected the level of cAMP left from the PDE hydrolysis reaction. The PDE activity is reversely correlated with the amount of cAMP left in the reaction and can be converted to the percent activity of an uninhibited control (100%).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 380.45, ALogP 4.26, HBA 5, HBD 0, PSA 52.83, QED 0.5
Compound (SMILES): CCOc1ccc(Nc2ccc(/C(=C3/C=C/C(=[N+](/CC)Cc4cccc(S(=O)(=O)[O-])c4)C=C3C)c3ccc(N(CC)Cc4cccc(S(=O)(=O)O)c4)cc3C)cc2)cc1
InChIKey: YVNQAIFQFWTPLQ-UHFFFAOYSA-N
Target: Albumin (SINGLE PROTEIN), Homo sapiens
UniProt: P02768
Assay: Binding affinity to human serum albumin immobilized on AR2G biosensor assessed as dissociation constant incubated for 3 mins by BLI assay
Measurement: Kd = 320 nM (pChEMBL 6.5)
Descriptors: MW 832.06, ALogP 9.31, HBA 8, HBD 2, PSA 139.08, QED 0.08
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCN2CCCCC2)cc1
InChIKey: NLVYWCRLGFDESU-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 303.49, ALogP 5.02, HBA 2, HBD 0, PSA 12.47, QED 0.63
Compound (SMILES): CC(CN1CCC2(CC1)COc1cc(OCc3c(Cl)cccc3Cl)ccc12)C(=O)O
InChIKey: ALKUQUPYTPNMBM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Functional Activity (Agonism) on Human S1P1 Receptors (Method B): The CHO-K1-Human S1P1-c-AMP assay was performed at Euroscreenfast, Brussels (Euroscreen, Human S1P1 coupling Gi/0, (Edg1) receptor, catalog n°: FAST-0197C, December 2009).Recombinant CHO-K1 cells expressing human S1P1, grown to mid-log Phase in culture media without antibiotics, detached, centrifuged and re-suspended. For agonist testing cells are mixed with compound and Forskolin and incubated at room temperature. Cells are lyses and cAMP concentration are estimated, according to the manufacturer specification, With the HTRF kit from CIS-BIO International (cat n°62AM2PEB).Agonistic effects of compounds are expressed as a percentage of the activity of the reference compound at its EC100 concentration, EC50 is calculated and results are reported as pEC50. Compounds were tested at a 10 points half log concentration range duplicated in 1 experiment.
Measurement: EC50 > 3162 nM (pChEMBL 5.5)
Descriptors: MW 450.36, ALogP 5.02, HBA 4, HBD 1, PSA 59, QED 0.67
Compound (SMILES): Nc1sc2ccccc2c1Oc1cccc(Cl)c1
InChIKey: DESLPMRDRQLKNY-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: In-vitro IDO1 Enzyme (Indoleamine 2,3-dioxygenase) Assay: Human indoleamine 2,3-dioxygenasel (hIDO1) catalyzes the oxidative cleavage of the pyrrole ring of the indole nucleus of tryptophan to yield N-formylkynurenine which can be converted to kynurenine (KYN) by deformylation. hIDO1 with an N-terminal His tag, expressed and purified from E. coli cells was procured from either Enzo LifeScienccs, NY, USA). Unless otherwise stated, all materials were procured from Sigma Aldrich, Mo., USA.The assay monitoring the conversion of L-tryptophan to KYN was carried out as follows. hIDO1 (10 nM) was incubated with tryptophan (30 μM) in the presence of ascorbic acid (20 mM), methylene blue (10 μM) and catalase (100 μg/mL) in potassium phosphate buffer (50 mM; pH 6.5) at 37C for 30 min. The reaction was terminated with 30% trichloroacetic acid (TCA) and further incubated at 65C for 15 min to fully convert N-formylkynurenine to KYN. The reaction mixture was then centrifuged to remove sediments and the KYN in the supernatant was estimated by UV-visible absorption spectroscopy at 360 nm using a Waters HPLC system fitted with a C-18 column or by LC/MS/MS. See, Sono, 1980, J. Biol. Chem., 255:1339-1345, which is herein incorporated by reference.Percent inhibition at each concentration of test compounds was determined by estimating the decrease in KYN with reference to the reaction control with 1% DMSO vehicle. Data were analyzed using nonlinear regression to generate IC50 values using Graph Pad Prism 5.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 275.76, ALogP 4.93, HBA 3, HBD 1, PSA 35.25, QED 0.72
Compound (SMILES): OC1CN(CCCOCCc2ccc3sccc3c2)C1
InChIKey: HQNACSFBDBYLJP-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Binding affinity to sigma 1 receptor (unknown origin)
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 291.42, ALogP 2.53, HBA 4, HBD 1, PSA 32.7, QED 0.8
Compound (SMILES): CCCCc1oc2ccccc2c1C(=O)c1cc(I)c(OCC[N+](C)(C)C)c(I)c1
InChIKey: CPUKLBDTNMMBMC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of recombinant HQ5-Halo-tagged KDM5A PHD3 domain (unknown origin) measured by fluorescence polarization assay
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 632.3, ALogP 6.3, HBA 3, HBD 0, PSA 39.44, QED 0.16
Compound (SMILES): CCc1cccc(Cl)c1CSc1ccc2c(c1)OCC21CCN(CCC(=O)O)CC1
InChIKey: NBHLHHDPYGECEF-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: In Vitro Functional Activity (Agonism) on Human S1P5 Receptors: The CHO-human-S1P5-Aeqorin assay was bought from Euroscreen, Brussels (Euroscreen, Technical dossier, Human Lysophospholid S1P5 (Edg8) receptor, DNA clone and CHO AequoScreen™ recombinant cell-line, catalog no: ES-593-A, September 2006). Human-S1P5-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P5 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 3 independent experiments were performed in single point's measurements.
Measurement: EC50 = 3.16 nM (pChEMBL 8.5)
Descriptors: MW 446.01, ALogP 5.4, HBA 4, HBD 1, PSA 49.77, QED 0.58
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCCN2CCC(C)CC2)cc1
InChIKey: OGOMRHOWEGLGBX-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 359.6, ALogP 6.44, HBA 2, HBD 0, PSA 12.47, QED 0.42
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCN2CCCCCC2)cc1
InChIKey: WUWSDBLNZJIRHW-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 = 609 nM (pChEMBL 6.210000038146973)
Descriptors: MW 317.52, ALogP 5.41, HBA 2, HBD 0, PSA 12.47, QED 0.59
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCN2CCCCCC2)cc1
InChIKey: NTMAHDOXEBKVCH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 = 1128 nM (pChEMBL 5.949999809265137)
Descriptors: MW 331.54, ALogP 5.8, HBA 2, HBD 0, PSA 12.47, QED 0.53
Compound (SMILES): Cn1cc(-c2ccncc2)c(-c2ccc(C#Cc3nccs3)cc2)n1
InChIKey: WZWNMFDITRIGMB-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: In Vitro Enzymatic Assay: The PDE enzymatic reaction was carried out in assay buffer (20 mM Tris-HCl pH7.5, 10 mM MgCl2, 0.1% bovine serum albumin) containing enzyme and substrate. The PDE enzymes concentration ranged from 10 pM-250 pM, depending on each enzyme's specific activity. The substrate cyclic nucleotide (cAMP or cGMP) concentration used in the assay was 20 nM for PDE10, and 100 nM for other PDEs. The inhibitory effect of compound was determined by incubating various concentration of inhibitor in the enzymatic assay. Typically, compound was serial diluted in DMSO then further diluted in assay buffer. Next, the compound at varying concentration was mixed with PDE enzyme. The reaction was initiated by addition of cyclic nucleotide substrate, and incubated for 60 minutes at 29 C. The reaction was stopped by addition of lysis buffer from assay kit. The cAMP-d2 and anti-cAMP cryptate in the lysis buffer detected the level of cAMP left from the PDE hydrolysis reaction. The PDE activity is reversely correlated with the amount of cAMP left in the reaction and can be converted to the percent activity of an uninhibited control (100%).
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 342.43, ALogP 4.01, HBA 5, HBD 0, PSA 43.6, QED 0.52
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCCCN2CCCC(C)C2)cc1
InChIKey: GBEKSZVQFLMGCF-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 373.63, ALogP 6.83, HBA 2, HBD 0, PSA 12.47, QED 0.37
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(OCc3c(F)cccc3Cl)ccc12
InChIKey: NHJVJIHHKZQOQD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: In Vitro Functional Activity (Agonism) on Human S1P5 Receptors: The CHO-human-S1P5-Aeqorin assay was bought from Euroscreen, Brussels (Euroscreen, Technical dossier, Human Lysophospholid S1P5 (Edg8) receptor, DNA clone and CHO AequoScreen™ recombinant cell-line, catalog no: ES-593-A, September 2006). Human-S1P5-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P5 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 3 independent experiments were performed in single point's measurements.
Measurement: EC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 419.88, ALogP 4.26, HBA 4, HBD 1, PSA 59, QED 0.76
Compound (SMILES): Clc1ccc2c(c1)[I+]c1ccccc1-2
InChIKey: AKXOLSKFZCRGEX-UHFFFAOYSA-N
Target: G-protein coupled receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P46089
Assay: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay
Measurement: EC50 = 921 nM (pChEMBL 6.039999961853027)
Descriptors: MW 313.55, ALogP 0.45, HBA 0, HBD 0, PSA 0, QED 0.53
Compound (SMILES): C/C(=C\CCP(=O)(O)OP(=O)(O)O)CO
InChIKey: YYYUHBYKZCBOPY-ZZXKWVIFSA-N
Target: Butyrophilin subfamily 3 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00481
Assay: Activation of BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of IL2-stimulated cell proliferation by measuring increase in CD3+ cells preincubated for 3 days followed by 11 days incubation post compound washout and subsequent IL2 stimulation for every 3 days measured after 14 days by flow cytometry
Measurement: EC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 260.12, ALogP 0.61, HBA 4, HBD 4, PSA 124.29, QED 0.41
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCN2CCC(C)CC2)cc1
InChIKey: UESFTYGAZXOTRU-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 345.57, ALogP 6.05, HBA 2, HBD 0, PSA 12.47, QED 0.48
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCN2CCCC(C)C2)cc1
InChIKey: ZNIBZXYWEHLBPD-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 345.57, ALogP 6.05, HBA 2, HBD 0, PSA 12.47, QED 0.48
Compound (SMILES): CCC(C)(C)c1ccc(OCCCCCCCN2CCCC(C)C2)cc1
InChIKey: FWWPKYOBCUXAGM-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 359.6, ALogP 6.44, HBA 2, HBD 0, PSA 12.47, QED 0.42
Compound (SMILES): CN(CCCCC(CO[N+](=O)[O-])O[N+](=O)[O-])Cc1ccc(COC(=O)NCc2ccc(C(=O)Nc3ccccc3N)cc2)cn1
InChIKey: CIOORWDADMZRRB-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 625.64, ALogP 3.73, HBA 12, HBD 3, PSA 214.32, QED 0.08
Compound (SMILES): Cc1cnc2c(N)c(C(=O)NCCc3ccc(N4CC5CCC(C4)N5)c(F)c3)sc2n1
InChIKey: CRWLSBQAYOCCCO-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: Ubiquitin-Rhodamine 110 Assay for USP25 Activity: The assay was performed in a final volume of 9 μL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 μM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 μM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 μM. Final substrate (Ub-Rh110: Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110]<<Km. 3 μL of 2× enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 μL of 2×Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 μL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 440.55, ALogP 2.63, HBA 7, HBD 3, PSA 96.17, QED 0.56
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(OCc3c(Cl)cccc3OC(F)(F)F)ccc12
InChIKey: RGAGCZDCRLIULM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Functional Activity (Agonism) on Human S1P1 Receptors (Method A): The CHO-K1-human-S1P1-Aeqorin assay was bought from Euroscreen Fast, Brussels (Euroscreen, Technical dossier, Human S1P1 (Edg1) receptor, DNA clone and CHO-K1 AequoScreen recombinant cell-line, catalog no: FAST-0197L, February 2010). Human-S1P1-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P1 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 2 independent experiments were performed in single point's measurements.
Measurement: EC50 = 6310 nM (pChEMBL 5.199999809265137)
Descriptors: MW 485.89, ALogP 5.02, HBA 5, HBD 1, PSA 68.23, QED 0.59
Compound (SMILES): O=C1c2ccccc2C(=O)c2c1nnn2-c1ccccc1
InChIKey: KXGSYSDSQRXROA-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of TDO (unknown origin) assessed as reduction in L-kynurenine formation using L-tryptophan as substrate incubated for 30 mins microplate spectrophotometry analysis
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 275.27, ALogP 2.04, HBA 5, HBD 0, PSA 64.85, QED 0.53
Compound (SMILES): NCc1ccc(Oc2ccc(S(=O)(=O)CC3CS3)cc2)cc1
InChIKey: GRRDUDJQILRRES-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Enzyme Inhibition Assay: Human recombinant active MMP-2 and MMP-7, and the catalytic domains of MMP-3 and MMP-14/MT1-MMP were purchased from EMD Chemicals, Inc. (San Diego, Calif., USA); human recombinant catalytic domains of MMP-1, MMP-8, and MMP-9 were purchased from Enzo Life Sciences, Inc. (Farmingdale, N.Y., USA); human recombinant active ADAM9 and ADAM10 were purchased from R&D Systems (Minneapolis, Minn., USA). Fluorogenic substrates MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 (for MMP-2, MMP-7, MMP-9 and MMP-14) and MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 (for MMP-3) were purchased from Peptides International (Louisville, Ky., USA); Mca-KPLGL-Dpa-AR-NH2 (for MMP-1, MMP-8 and ADAM10) and Mca-PLAQAV-Dpa-RSSSR-NH2 (for ADAM9) were purchased from R&D Systems (Minneapolis, Minn., USA). The Km values for MMP-2, MMP-9 and MMP-14 were the same as previously reported by Gooyit et al. ((2013) J. Med. Chem. 56(20):8139-8150). Inhibitor stock solutions (10 mM) were prepared freshly in DMSO before enzyme inhibition assays. We followed the same methodology for enzyme inhibition studies as reported before by Page-McCaw et al. ((2007) Nat Rev Mol Cell Biol 8(3):221-233). Enzyme inhibition studies were carried out using a Cary Eclipse fluorescence spectrophotometer (Varian, Walnut Creek, Calif., USA). Compound 1 was stable in the buffers used in the kinetic assays.
Measurement: Ki = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 335.45, ALogP 2.83, HBA 5, HBD 1, PSA 69.39, QED 0.82
Compound (SMILES): CC(C)(O)c1cccn2c(C3(c4ccc(Cl)cc4)CC3)nnc12
InChIKey: PTIFVLOBVCIMKL-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 327.82, ALogP 3.69, HBA 4, HBD 1, PSA 50.42, QED 0.8
Compound (SMILES): c1ccc([C@@H]2C[C@H]2NC2CCNCC2)cc1
InChIKey: BASFYRLYJAZPPL-UONOGXRCSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 (unknown origin)
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 216.33, ALogP 1.88, HBA 2, HBD 2, PSA 24.06, QED 0.81
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(C#Cc3ccccc3)ccc12
InChIKey: OWHUUJZBNSHXSC-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Functional Activity (Agonism) on Human S1P1 Receptors (Method A): The CHO-K1-human-S1P1-Aeqorin assay was bought from Euroscreen Fast, Brussels (Euroscreen, Technical dossier, Human S1P1 (Edg1) receptor, DNA clone and CHO-K1 AequoScreen recombinant cell-line, catalog no: FAST-0197L, February 2010). Human-S1P1-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P1 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 2 independent experiments were performed in single point's measurements.
Measurement: EC50 < 31623 nM (pChEMBL 4.5)
Descriptors: MW 361.44, ALogP 3.29, HBA 3, HBD 1, PSA 49.77, QED 0.85
Compound (SMILES): CC(CN1CCC2(CC1)COc1cc(OCc3c(Cl)cccc3Cl)ccc12)C(=O)O
InChIKey: ALKUQUPYTPNMBM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: In Vitro Functional Activity (Agonism) on Human S1P3 Receptors: The CHO-human-S1P3-Aeqorin assay (CHO/Gal6/AEQ/h-S1P3) was established at Solvay Pharmaceuticals. The plasmid DNA coding for the S1P3 receptor (accession number in GenBank N. Mex._005226 was purchased from UMR cDNA resource Centre (Rolla, Mo.). The pcDNA3.1/hS1P3 construct carrying the mitochondrially targeted apo-Aeqorin and Ga16 protein was transfected in CHO K1 cell-line.Human-S1P3-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P3 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 3 independent experiments were performed in single point's measurements.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 450.36, ALogP 5.02, HBA 4, HBD 1, PSA 59, QED 0.67
Compound (SMILES): CCCCc1oc2ccccc2c1C(=O)c1cc(I)c(OCC[N+](C)(C)C)c(I)c1
InChIKey: CPUKLBDTNMMBMC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant HQ5-Halo-tagged KDM4A tudor domain (unknown origin) measured by fluorescence polarization assay
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 632.3, ALogP 6.3, HBA 3, HBD 0, PSA 39.44, QED 0.16
Compound (SMILES): CCc1cccc(Cl)c1CSc1ccc2c(c1)OCC21CCN(CCC(=O)O)CC1
InChIKey: NBHLHHDPYGECEF-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Functional Activity (Agonism) on Human S1P1 Receptors (Method A): The CHO-K1-human-S1P1-Aeqorin assay was bought from Euroscreen Fast, Brussels (Euroscreen, Technical dossier, Human S1P1 (Edg1) receptor, DNA clone and CHO-K1 AequoScreen recombinant cell-line, catalog no: FAST-0197L, February 2010). Human-S1P1-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P1 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 2 independent experiments were performed in single point's measurements.
Measurement: EC50 = 158 nM (pChEMBL 6.800000190734863)
Descriptors: MW 446.01, ALogP 5.4, HBA 4, HBD 1, PSA 49.77, QED 0.58
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(OCc3c(F)cccc3Cl)ccc12
InChIKey: NHJVJIHHKZQOQD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: In Vitro Functional Activity (Agonism) on Human S1P1 Receptors (Method B): The CHO-K1-Human S1P1-c-AMP assay was performed at Euroscreenfast, Brussels (Euroscreen, Human S1P1 coupling Gi/0, (Edg1) receptor, catalog no: FAST-0197C, December 2009).Recombinant CHO-K1 cells expressing human S1P1, grown to mid-log Phase in culture media without antibiotics, detached, centrifuged and re-suspended. For agonist testing cells are mixed with compound and Forskolin and incubated at room temperature. Cells are lyses and cAMP concentration are estimated, according to the manufacturer specification, With the HTRF kit from CIS-BIO International (cat no 62AM2PEB).Agonistic effects of compounds are expressed as a percentage of the activity of the reference compound at its EC100 concentration, EC50 is calculated and results are reported as pEC50. Compounds were tested at a 10 points half log concentration range duplicated in 1 experiment.
Measurement: EC50 < 3162 nM (pChEMBL 5.5)
Descriptors: MW 419.88, ALogP 4.26, HBA 4, HBD 1, PSA 59, QED 0.76
Compound (SMILES): C/C(=C\CCP(=O)(O)OP(=O)(O)O)CO
InChIKey: YYYUHBYKZCBOPY-ZZXKWVIFSA-N
Target: Butyrophilin subfamily 3 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00481
Assay: Activation of BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of IL2-stimulated IFNgamma production measured after 48 hrs by ELISA
Measurement: EC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 260.12, ALogP 0.61, HBA 4, HBD 4, PSA 124.29, QED 0.41
Compound (SMILES): CN(CCCCC(CO[N+](=O)[O-])O[N+](=O)[O-])Cc1ccc(COC(=O)NCc2ccc(C(=O)Nc3ccccc3N)cc2)cn1
InChIKey: CIOORWDADMZRRB-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 1220 nM (pChEMBL 5.909999847412109)
Descriptors: MW 625.64, ALogP 3.73, HBA 12, HBD 3, PSA 214.32, QED 0.08
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(OCc3c(Cl)cccc3OC(F)(F)F)ccc12
InChIKey: RGAGCZDCRLIULM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: In Vitro Functional Activity (Agonism) on Human S1P3 Receptors: The CHO-human-S1P3-Aeqorin assay (CHO/Gα16/AEQ/h-S1P3) was established at Solvay Pharmaceuticals. The plasmid DNA coding for the S1P3 receptor (accession number in GenBank NM_005226 was purchased from UMR cDNA resource Centre (Rolla, Mo.). The pcDNA3.1/hS1P3 construct carrying the mitochondrially targeted apo-Aeqorin and Gal6 protein was transfected in CHO K1 cell-line.Human-S1P3-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P3 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 3 independent experiments were performed in single point's measurements.
Measurement: EC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 485.89, ALogP 5.02, HBA 5, HBD 1, PSA 68.23, QED 0.59
Compound (SMILES): NCc1ccc(Oc2ccc(S(=O)(=O)CC3CS3)cc2)cc1
InChIKey: GRRDUDJQILRRES-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition Assay: The term selective inhibitor as used in reference to MMPs refers to an inhibitor that inhibits the enzymatic activity of one MMP in the presence of one or more other MMPs, typically by at least one order of magnitude, for example, with respect to the Ki. The methods used to obtain Ki data are known in the art and are described, for example, by Brown et al., J. Amer. Chem. Soc. 2000, 122(28), 6799-6800, and the references cited therein. Additional useful assays and techniques are described in U.S. Patent Publication No. 2009/0209615 (Lipton et al.), which is incorporated herein by reference in its entirety.
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 335.45, ALogP 2.83, HBA 5, HBD 1, PSA 69.39, QED 0.82
Compound (SMILES): CC(C)(O)c1cccn2c(C3(c4ccc(Cl)cc4)CC3)nnc12
InChIKey: PTIFVLOBVCIMKL-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 327.82, ALogP 3.69, HBA 4, HBD 1, PSA 50.42, QED 0.8
Compound (SMILES): c1ccc([C@@H]2C[C@H]2NC2CCNCC2)cc1
InChIKey: BASFYRLYJAZPPL-UONOGXRCSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant LSD1 (unknown origin) preincubated for 10 mins in presence of H3K4Me2 measured after 30 mins by measuring fluorescence intensity by fluorescence based microplate reader
Measurement: IC50 = 18.6 nM (pChEMBL 7.730000019073486)
Descriptors: MW 216.33, ALogP 1.88, HBA 2, HBD 2, PSA 24.06, QED 0.81
Compound (SMILES): O=C(O)CCN1CCC2(CC1)COc1cc(C#Cc3ccccc3)ccc12
InChIKey: OWHUUJZBNSHXSC-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: In Vitro Functional Activity (Agonism) on Human S1P3 Receptors: The CHO-human-S1P3-Aeqorin assay (CHO/Gα16/AEQ/h-S1P3) was established at Solvay Pharmaceuticals. The plasmid DNA coding for the S1P3 receptor (accession number in GenBank NM_005226 was purchased from UMR cDNA resource Centre (Rolla, Mo.). The pcDNA3.1/hS1P3 construct carrying the mitochondrially targeted apo-Aeqorin and Gal6 protein was transfected in CHO K1 cell-line.Human-S1P3-Aequorin cells express mitochondrial targeted apo-Aequorin. Cells have to be loaded with coelanterazine, in order to reconstitute active Aequorin. After binding of agonists to the human S1P3 receptor the intracellular calcium concentration increases and binding of calcium to the apo-Aequorin/coelenterazine complex leads to an oxidation reaction of coelenterazine, which results in the production of apo-Aequorin, coelenteramide, CO2 and light (□max 469 nm). This luminescent response is dependent on the agonist concentration. Luminescence is measured using the MicroBeta Jet (Perkin Elmer). Agonistic effects of compounds are expressed as pEC50. Compounds were tested at a 10 points half log concentration range, and 3 independent experiments were performed in single point's measurements.
Measurement: EC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 361.44, ALogP 3.29, HBA 3, HBD 1, PSA 49.77, QED 0.85