lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COC(=O)N[C@H](C(=O)N[C@H](c1ccc([C@@H](CO)N(CCC(C)(C)C)S(=O)(=O)c2ccc3ocnc3c2)s1)C(F)(F)F)C(c1ccccc1)c1ccccc1
InChIKey: LUEGLYCGJCCYBI-WEQWWUEYSA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04585
Assay: Inhibition Assay: The inhibition of WT HIV-1 protease was studied using the reaction of the protease (expressed in Eschericia coli) with a peptide substrate [Val-Ser-Gln-Asn-(betanaphthyl)Ala-Pro-Ile-Val (SEQ ID NO:1)]. Compounds were tested using Procedure A. In Procedure A, the test compound was first preincubated with the enzyme in assay buffer (50 mM sodium acetate, pH 5.5, 100 mM NaCl, and 0.1% BSA) for 30 minutes at room temperature. Substrate was then added to 400 micromolar in a total volume of 80 microliters containing 10 picomolar HIV-1 protease and the reaction was incubated for 1 hour at 30° C. The reaction was quenched with the addition of 120 microliters of 10% phosphoric acid. The product formation was determined after separation of product and substrate on a Zorbax Eclipse XDB-C18 column (Agilent Technologies, Santa Clara, Calif.) connected to an Agilent 1100 high performance liquid chromatography system with fluorescence detection (excitation 270 nanometer and emission 330 nanometer).
Measurement: IC50 = 1.95 nM (pChEMBL 8.710000038146973)
Descriptors: MW 786.9, ALogP 7.33, HBA 9, HBD 3, PSA 151.07, QED 0.11
Compound (SMILES): CCNC(=O)[C@@H]1C[C@H]2C[C@H]2N1C(=O)Nc1cn(C(N)=O)c2ccccc12
InChIKey: BYYKBPPGVSMJJW-KMUNFCNLSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: In Vitro Assay: Recombinant human factor D (expressed in E. coli and purified using standard methods) at 10 nM concentration is incubated with test compound at various concentrations for 1 hour at room temperature in 0.1 M Hepes buffer, pH 7.5, containing 1 mM MgCl2, 1 M NaCl and 0.05% CHAPS. A synthetic substrate Z-Lys-thiobenzyl and 2,4-dinitrobenzenesulfonyl-fluoresceine are added to final concentrations of 200 μM and 25 μM, respectively. The increase in fluorescence is recorded at excitation of 485 nm and emission at 535 nm in a microplate spectrofluorimeter.
Measurement: IC50 = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 355.4, ALogP 1.7, HBA 4, HBD 3, PSA 109.46, QED 0.78
Compound (SMILES): CC(Nc1ncc(F)c(N2C(=O)OC[C@@H]2[C@@H](C)O)n1)c1nc(-c2ccc(F)c(F)c2)no1
InChIKey: CZKHIFLFSUFAEU-MNAQOFIPSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+(NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 1510 nM (pChEMBL 5.820000171661377)
Descriptors: MW 450.38, ALogP 2.82, HBA 9, HBD 2, PSA 126.5, QED 0.58
Compound (SMILES): Cc1csc(-c2c(N[C@@H]3CCCNC3)nc(N3CCOCC3)[nH]c2=O)n1
InChIKey: PTFQSULPOOXZSE-GFCCVEGCSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: IMAP technology (Molecular Devices): A 20 ul reaction mixture contains 10 mM TriHCl, pH 7.2, 0.5 nM GST tagged IRAK4 (SignalChem), 100 nM fluorescent peptide substrate (RP7030, Molecular Devices), 100 uM ATP, 1 mM DTT, 1 mM MgCl2, and 0.01% Tween 20. The reaction is initiated by the addition of ATP. After incubation for 30 minutes at 25° C., 60 ul of Progressive IMAP Reagent (Molecular Devices) is added to stop the reaction. Change in RP7030's FP is determined by a FP reader (Analyst HT, LJL BioSystems).
Measurement: IC50 = 554 nM (pChEMBL 6.260000228881836)
Descriptors: MW 376.49, ALogP 1.2, HBA 8, HBD 3, PSA 95.17, QED 0.74
Compound (SMILES): CC(C)n1cc(-c2cc(Nc3nccc(C(F)(F)F)n3)cc(-c3cnc([C@@]4(O)CC[C@H](C(=O)O)C(C)(C)C4)s3)c2)cn1
InChIKey: ZARYYXTZVLZMLI-LYZGTLIUSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Homogeneous Time-Resolved Fluorescence (HTRF) Assay: A recombinant GST-hSYK fusion protein was used to measure potency of compounds to inhibit human Syk activity. The recombinant human GST-SYK (Carna Biosciences #08-176) (5 pM final concentration) was incubated with various concentrations of the inhibitor diluted in DMSO (0.1% final concentration) for 10 minutes at room temperature in 15 mM Tris-HCl (pH 7.5), 0.01% tween 20, 2 mM DTT in 384 well plate format. To initiate the reaction the biotinylated substrate peptide (250 nM final concentration) that contains the phosphorylation site for Syk was added with magnesium (5 mM final concentration) and ATP (25 uM final concentration). Final volume of the reaction was 10 uL. Phosphorylation of the peptide was allowed to proceed for 45' at room temperature. To quench the reaction and detect the phosphorylated product, 2 nM of a Europium-anti-phosphotyrosine antibody (Perkin Elmer #AD0161) and 70 nM SA-APC (Perkin-Elmer #CR130-100) were added together in 15 mM Tris pH 7.5, 40 mM EDTA, 0.01% tween 20. Final volume of the quenching solution was 10 uL. The resulting HTRF signal was measured after 30 minutes on an EnVision (Perkin-Elmer) reader using a time-resolved fluorescence protocol.
Measurement: IC50 = 149.1 nM (pChEMBL 6.829999923706055)
Descriptors: MW 600.67, ALogP 6.91, HBA 9, HBD 3, PSA 126.05, QED 0.21
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]nc(N(C)C)c2cn1)c1ccc(F)cc1
InChIKey: WOEPPLCPFHYYLU-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 nL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-SFAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.5 nM hERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP.
Measurement: IC50 = 17.29 nM (pChEMBL 7.760000228881836)
Descriptors: MW 342.38, ALogP 3.05, HBA 4, HBD 3, PSA 85.94, QED 0.68
Compound (SMILES): COc1ccc(CNc2cc(OC[C@H]3C[C@@H]3c3ccc(OC)cn3)nn(C)c2=O)cc1
InChIKey: HSBXMTGRYZNTGY-APWZRJJASA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The fluorescence polarization assay for cyclic nucleotide phosphodiesterases was performed using an IMAP® FP kit supplied by Molecular Devices, Sunnyvale, Calif. (product #R8139). IMAP® technology has been applied previously to phosphodiesterase assays (Huang, W., et al., J. Biomol Screen, 2002, 7: 215).
Measurement: Ki = 0.021 nM (pChEMBL 10.680000305175781)
Descriptors: MW 422.49, ALogP 2.99, HBA 8, HBD 1, PSA 87.5, QED 0.57
Compound (SMILES): O=C([C@@H]1CCCN(c2ccc3nc(Cc4ccc(Cl)cc4)[nH]c3n2)C1)N1CCCC1
InChIKey: LJAOJLPLYUEWBW-QGZVFWFLSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: In Vitro DGAT2 Assay: For determination of IC50 values, the reactions were carried out in 384-well white Polyplates (Perkin Elmer) in a total volume of 20 uL. To 1 uL of compounds dissolved in 100% DMSO and spotted at the bottom of each well, 5 uL of 0.04% bovine serum albumin (BSA) (fatty acid free, Sigma Aldrich) was added and the mixture was incubated at room temperature for 20 minutes. To this mixture, 10 uL of hDGAT2 membrane fraction (0.01 mg/mL) diluted in 100 mM Hepes-NaOH, pH 7.4, 20 mM MgCl2 containing 200 nM methyl arachidonyl fluorophosphonate (Cayman Chemical; dried from ethyl acetate stock solution under argon gas and dissolved in DMSO as 5 mM stock) was added. After this mixture was preincubated at room temperature for 2 hours, DGAT2 reactions were initiated by the addition of 4 uL of substrates containing 30 uM [1-14C]decanoyl-CoA (custom-synthesized by Perkin Elmer, 50 mCi/mmol) and 125 uM 1,2-didecanoyl-sn-glycerol (Avanti Polar Lipids) dissolved in 12.5% acetone. The reaction mixtures were incubated at room temperature for 40 min and the reactions were stopped by addition of 5 uL of 1% H3PO4. After the addition of 45 uL MicroScint-E (Perkin-Elmer), plates were sealed with Top Seal-A covers (Perkin-Elmer) and phase partitioning of substrates and products was achieved using a HT-91100 microplate orbital shaker (Big Bear Automation, Santa Clara, Calif.). Plates were centrifuged at 2,000×g for 1 min in an Allegra 6R Centrifuge (Beckman Coulter) and then were sealed again with fresh covers before reading in a 1450 Microbeta Wallac Trilux Scintillation Counter (Perkin Elmer). DGAT2 activity was measured by quantifying the generated product [14C]tridecanoylglycerol in the upper organic phase.
Measurement: IC50 = 188 nM (pChEMBL 6.730000019073486)
Descriptors: MW 423.95, ALogP 4.04, HBA 4, HBD 1, PSA 65.12, QED 0.69
Compound (SMILES): Cc1cc(-c2nc(-c3ccc(Cl)c(Cl)c3)n3c2CCO[C@H](C)C3)cc(CF)n1
InChIKey: WENVDBYSQOVWDR-CYBMUJFWSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: [35S]GTPgammaS Binding Assay: The frozen cell membrane fraction prepared as described above was thawed before use, and the resultant was diluted with a buffer for a binding assay (final concentrations: 20 mM HEPES, 100 mM NaCl, 1 mM MgCl2, 3 uM GDP, 300 ug/mL saponin, 0.1% BSA). The compound of each example was added to a cell membrane fraction containing 1.8 to 3 ug/assay of membrane protein on a plate, followed by incubation at room temperature for 30 minutes. Thereafter, with glutamic acid (in a final concentration of 10 uM) added thereto, incubation was performed at room temperature for 15 minutes, and thereafter, [35S]GTPγS (in a final concentration of 0.8 kBq) and 588 ug WGA-SPA beads were added thereto, followed by incubation at room temperature for 1 hour. After the incubation, the plate was subjected to the centrifugal separation at 2,500 rpm and room temperature, and then, membrane cell binding radioactivity was measured with a top count. A [35S]GTPγS binding amount obtained in the presence of glutamic acid was defined as specific binding. On the basis of ratios of inhibiting the specific binding at various concentrations of the compounds of the respective examples, inhibition curves were obtained. Concentrations of the compounds of the respective examples at which the specific [35S]GTPγS binding amount was suppressed by 50% (IC50 values) were calculated on the basis of the inhibition curves.
Measurement: IC50 = 13.2 nM (pChEMBL 7.880000114440918)
Descriptors: MW 420.32, ALogP 5.66, HBA 4, HBD 0, PSA 39.94, QED 0.55
Compound (SMILES): CCOC(=O)CNC(=O)C[C@H]1C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N(CC2CC2)C1=O
InChIKey: ZDHJFEPXXMSIRC-ROSOWXQZSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Homogenous Time-Resolved Fluorescence Assay (HTRF1 Assay): The standard assay conditions for the in vitro HTRF assay consisted of a 50 ul total reaction volume in black 384-well Costar polypropylene plates in 1xPBS buffer pH 7.4, 1 mM DTT, 0.1% BSA, 2.5 nM GST-hMDM2 (aa 1-188), 5 nM biotinylated-p53 (aa 1-83), 1.8 nM SA-XLent (Cisbio; Bedford, Mass.), 0.6 nM anti-GST cryptate monoclonal antibody (Cisbio; Bedford, Mass.) and 200 mM KF. Amino acid residues 1-188 of human MDM2 were expressed as an amino-terminal glutathione-S-transferase (GST) fusion protein (GST-hMDM2) in Escherichia coli. Residues 1-83 of human p53 were expressed as an amino-terminal AviTag-TrxA-6-His fusion protein (biotinylated p53) in E. coli. Each protein was purified from cell paste by affinity chromatography.Specifically, 10 uL of GST-hMDM2 was incubated with 10 ul of diluted compound (various concentrations, serially diluted) in 10% DMSO for 20 minutes at room temperature. 20 uL of biotinylated-p53 was added to the GST-hMDM2+compound mixture, and then incubated at room temperature for 60 min. 10 uL of detection buffer consisting of SA-XLent, anti-GST cryptate antibody and KF was added to GST-hMDM2, biotinylated-p53 and compound reaction and left at room temperature to reach equilibrium for >4 hrs. The final concentration of DMSO in the reaction was 2%. Time-resolved fluorescence readings were measured on a microplate multilabel reader. Percentage of inhibition was calculated relative to nutlin-3.
Measurement: IC50 = 2380 nM (pChEMBL 5.619999885559082)
Descriptors: MW 517.45, ALogP 5.15, HBA 4, HBD 1, PSA 75.71, QED 0.47
Compound (SMILES): COc1ccc([C@H]2C[C@@H]2COc2cc(NC(=O)c3cnn(C)c3Cl)c(=O)n(C)n2)nc1
InChIKey: CBGFJLZAGCOPLQ-YPMHNXCESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The fluorescence polarization assay for cyclic nucleotide phosphodiesterases was performed using an IMAP® FP kit supplied by Molecular Devices, Sunnyvale, Calif. (product #R8139). IMAP® technology has been applied previously to phosphodiesterase assays (Huang, W., et al., J. Biomol Screen, 2002, 7: 215).
Measurement: Ki = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 444.88, ALogP 2.01, HBA 9, HBD 1, PSA 113.16, QED 0.59
Compound (SMILES): COc1ccc(-c2nc(-c3cc(C)nc(C)c3)c3n2C[C@@H](C)OCC3)cc1OC(F)(F)F
InChIKey: AIXGBGVZTRXQPV-OAHLLOKOSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: [35S]GTPgammaS Binding Assay: The frozen cell membrane fraction prepared as described above was thawed before use, and the resultant was diluted with a buffer for a binding assay (final concentrations: 20 mM HEPES, 100 mM NaCl, 1 mM MgCl2, 3 uM GDP, 300 ug/mL saponin, 0.1% BSA). The compound of each example was added to a cell membrane fraction containing 1.8 to 3 ug/assay of membrane protein on a plate, followed by incubation at room temperature for 30 minutes. Thereafter, with glutamic acid (in a final concentration of 10 uM) added thereto, incubation was performed at room temperature for 15 minutes, and thereafter, [35S]GTPγS (in a final concentration of 0.8 kBq) and 588 ug WGA-SPA beads were added thereto, followed by incubation at room temperature for 1 hour. After the incubation, the plate was subjected to the centrifugal separation at 2,500 rpm and room temperature, and then, membrane cell binding radioactivity was measured with a top count. A [35S]GTPγS binding amount obtained in the presence of glutamic acid was defined as specific binding. On the basis of ratios of inhibiting the specific binding at various concentrations of the compounds of the respective examples, inhibition curves were obtained. Concentrations of the compounds of the respective examples at which the specific [35S]GTPγS binding amount was suppressed by 50% (IC50 values) were calculated on the basis of the inhibition curves.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 447.46, ALogP 5.1, HBA 6, HBD 0, PSA 58.4, QED 0.56
Compound (SMILES): CC(C)Nc1cc(-n2ccc(-c3ccnnc3)n2)ncc1C(=O)NC[C@@H](F)C(C)(C)O
InChIKey: CWTAFFRTPZWRJY-GOSISDBHSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 L prepared from 15 L additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.2, 10 mM MgCl2, 0.015% Brij 35 and 4 mM DTT). The reaction was initiated by the combination of IRAK4 with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 min. and terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentrations of reagents in the assays are ATP, 500 μM; FL-IPTSPITTTYFFFKKK peptide 1.5 μM; IRAK4, 0.6 nM; and DMSO, 1.6%.
Measurement: IC50 = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 427.48, ALogP 2.38, HBA 8, HBD 3, PSA 117.85, QED 0.51
Compound (SMILES): C[C@@H]1CCC[C@H](N2CCC(c3c(C(F)(F)F)ccc(Cl)c3F)=CC2=O)c2cc(ccn2)-c2cc(C(=O)O)ccc2NC1=O
InChIKey: OUXKGHOTTHIOQL-CPJLOUKISA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: In Vitro Assay: Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4 containing 145 mM NaCl, 5 mM KCl, and 0.1% PEG 8000 (polyethylene glycol; JT Baker or Fisher Scientific). Determinations were made using purified human Factor XIa at a final concentration of 25-200 pM (Haematologic Technologies) and the synthetic substrate S-2366 (pyroGlu-Pro-Arg-pNA; CHROMOGENIX® or AnaSpec) at a concentration of 0.0002-0.001 M.
Measurement: Ki = 0.44 nM (pChEMBL 9.359999656677246)
Descriptors: MW 616.01, ALogP 7.37, HBA 4, HBD 2, PSA 99.6, QED 0.3
Compound (SMILES): COc1n[nH]c2cc(NC(=O)N[C@H](C)c3ccc(F)cc3)nc(CO)c12
InChIKey: SDGFCKHWIGGEOX-SECBINFHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 nL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-SFAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 359.36, ALogP 2.48, HBA 5, HBD 4, PSA 112.16, QED 0.56
Compound (SMILES): Cn1ccc([C@H]2C[C@@H]2COc2cc(NCc3ccnn3C)c(=O)n(C)n2)n1
InChIKey: VZMJLQLYCOSUJF-OCCSQVGLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The fluorescence polarization assay for cyclic nucleotide phosphodiesterases was performed using an IMAP® FP kit supplied by Molecular Devices, Sunnyvale, Calif. (product #R8139). IMAP® technology has been applied previously to phosphodiesterase assays (Huang, W., et al., J. Biomol Screen, 2002, 7: 215).
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 369.43, ALogP 1.04, HBA 9, HBD 1, PSA 91.79, QED 0.67
Compound (SMILES): COc1cc(F)c(-c2nc(C(=O)Nc3cnn(C)c3[C@@H]3CC[C@@H](N)[C@H](F)CO3)ccc2F)c(F)c1
InChIKey: JDGJVHTXRIDZOI-MDZRGWNJSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: PIM Kinase Binding Assay: LC3K assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO. PIM reactions were carried out in a final volume of 10 μL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 μL 2×ATP and test compound to 5 μL of 2× enzyme and FAM-peptide, contained 20 pM PIM1, 50 pM PIM2, or 55 pM PIM3, 1 μM FAM-peptide, and 10 μM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 μL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000® (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of −500V, an upstream voltage of −2150V, and a screening pressure of −1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm.
Measurement: Ki = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 493.46, ALogP 3.68, HBA 7, HBD 2, PSA 104.29, QED 0.53
Compound (SMILES): CC(C)Nc1cc(-n2ncc3cnc(N)nc32)ncc1C(=O)NC[C@@H](F)C(C)(C)O
InChIKey: WSVZCYLWHXLJLL-CQSZACIVSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 L prepared from 15 L additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.2, 10 mM MgCl2, 0.015% Brij 35 and 4 mM DTT). The reaction was initiated by the combination of IRAK4 with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 min. and terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentrations of reagents in the assays are ATP, 500 μM; FL-IPTSPITTTYFFFKKK peptide 1.5 μM; IRAK4, 0.6 nM; and DMSO, 1.6%.
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 416.46, ALogP 1.45, HBA 9, HBD 4, PSA 143.87, QED 0.45
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCc4cc6c(cc4Cl)OCO6)[C@@H](C2)[N+](C)(CC2CC2)CC[C@]315
InChIKey: JJOPKJOJGNOCTM-ILFZRLQGSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose-displacement binding assays for -opioid receptors used 0.3 nM [3H]-diprenorphine (Perkin Elmer, Shelton, Conn.), with 5 mg membrane protein/well in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 2 hr at room temperature. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.), presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by performing three filtration washes with 500 ul of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hours. BetaScint scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added (50 ul/well), and plates were counted using a Packard Top-Count.
Measurement: Ki = 162.64 nM (pChEMBL 6.789999961853027)
Descriptors: MW 595.16, ALogP 5.66, HBA 6, HBD 0, PSA 55.38, QED 0.37
Compound (SMILES): O=C(NCC1(CO)COC1)c1cc(NC(=O)c2cc(-c3ccccn3)c(Cl)cc2Cl)n(-c2ccccc2)n1
InChIKey: UQLYYQWBABNRMG-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Cell Based Assay: TRKA co-expressed with p75: The assays are based upon DiscoveRx's proprietary Enzyme Fragment Complementation (EFC) technology. In the case of the TRK cell lines, the enzyme acceptor (EA) protein is fused to a SH2 protein and the TRK receptor of interest has been tagged with a Prolink tag. Cryopreserved PathHunter cells are used from either in-house produced batches or bulk batches bought directly from DiscoveRx. Cryopreserved cells are resuscitated, spun 1000 rpm for 4 min to remove freezing media, and resuspended in MEM+0.5% horse serum (both Invitrogen) to 5e^5 cells/ml. The cells are then plated using a Multidrop into Greiner white tissue culture treated plates at 20 μl/well and incubated for 24 h at 37 °C., 5% CO2, high humidity. On the day of the assay, the cell plates are allowed to cool to room temperature for 30 min prior to the assay. 4 mM stock solutions of test compounds are prepared and serially diluted in 100% DMSO. A standard curve using the compound of Example 135, WO2005/116035 at a top concentration of 150 μM is also prepared on each test plate. High percentage effect (HPE) is defined by 150 μM of the compound of Example 135, WO2005/116035 and 0% effect (ZPE) is defined by 100% DMSO. Plates containing 1 μl of serially diluted compound, standard and HPE/ZPE are diluted 1/66 in assay buffer (PBS minus Ca2+, minus Mg2+ with 0.05% pluronic F127) using a Wellmate. Using a Platemate Plus, 5 μl of 1/66 diluted test compounds is then transferred to the cell plate and allowed to reach equilibrium by incubating for 30 min at room temperature before addition of agonist stimulus: 10 μl/well of 2 nM (0.571 nM FAC) of the cognate neurotrophin (Peprotech) diluted in agonist buffer (HBSS with 0.25% BSA). Final assay concentration of the test compounds is 8.66 μM, (the compound of Example 135, WO2005/116035 FAC is 0.325 μM). The plates are left at room temperature for a further 2 hours before addition of 10 μl of the DiscoveRx PathHunter detection reagent (made up by adding 1 part Galacton Star, 5 parts Emerald II and 19 parts Cell Assay Buffer as per the manufacturer's instructions). After reagent addition, plates are covered and incubated at room temperature for 60 minutes. Luminescence signal is read using an Envision.
Measurement: IC50 = 10.9 nM (pChEMBL 7.960000038146973)
Descriptors: MW 552.42, ALogP 4.23, HBA 7, HBD 3, PSA 118.37, QED 0.3
Compound (SMILES): Nc1cnc(-c2ccc(-c3ccccc3O[C@@H]3CCCNC3)cc2F)cn1
InChIKey: LOKBDTUZBZMZCJ-OAHLLOKOSA-N
Target: Flap endonuclease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P39748
Assay: Binding Assay: The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand. [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode. Data are expressed as a HTRF ratio. For human FLAP binding assays, data are analyzed with 3DX Explorer software. A ratio is calculated with the relative light units at 520 nm over the relative light units at 495 nm. For analysis, data from multiple runs are averaged and each compound may be tested in 2 to 20 runs. Each run comprises two plates and each plate includes duplicates. Data from each plate is averaged and data are imported into 3DX. The data from multiple runs are aggregated as the average of duplicates of the calculated ratios in order to calculate Ki and IC50 values.
Measurement: Ki = 1268 nM (pChEMBL 5.900000095367432)
Descriptors: MW 364.42, ALogP 3.66, HBA 5, HBD 2, PSA 73.06, QED 0.74
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@@](c3ccc(C(O)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC1
InChIKey: KJQFBTHRWLTPCF-XMMPIXPASA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Scintillation Proximity Assay (SPA): The binding of potential ligands to RORγ is measured by competition with [3H] 25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA) binding assay. The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 ug/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 uM to 0.28 nM for 10 min at room temperature in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% Glycerol (Sigma Cat#G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat #RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce [3H] 25-hydroxycholesterol specific binding by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 1702 nM (pChEMBL 5.769999980926514)
Descriptors: MW 624.58, ALogP 4.3, HBA 5, HBD 1, PSA 94.99, QED 0.4
Compound (SMILES): C[C@@H](Nc1cc(NC2CC2)n2ncc(/C=C3\NC(=O)NC3=O)c2n1)C1CC1
InChIKey: ISOROGJOHADWEE-JHFYRWCBSA-N
Target: Casein kinase II subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P67870
Assay: Inhibition Assay: 5 uM ATP: Test compounds dissolved and diluted in DMSO (2 μl) were added to a reaction mixture comprising 10 μl of 5× Reaction Buffer (40 mM MOPS pH 7.0, 5 mM EDTA), 10 μl of recombinant human PIM2 solution (4 ng PIM-2 dissolved in dilution buffer (20 mM MOPS pH 7.0; EDTA 1 mM; 5% Glycerol; 0.01% Brij 35; 0.1%; 0.1% 2-mercaptoethanol; 1 mg/ml BSA)) and 8 ul of water. Reactions were initiated by the addition of 10 ul of ATP Solution (49% (15 mM MgCl2; 5 uM ATP) 1% ([γ-33P]ATP: Stock 1 mCi/100 μl; 3000 Ci/mmol (Perkin Elmer)) and 10 ul of substrate peptide solution (RSRSSYPAGT (SEQ ID NO.: 6), dissolved in water at a concentration of 1 mM), Reactions were maintained for 10 min at 30° C. The reactions were quenched with 100 ul of 0.75% Phosphoric acid, then transferred to and filtered through a Phosphocellulose filter plate (Millipore, MSPH-N6B-50). After washing each well 4 times with 0.75% Phosphoric acid, scintillation fluid (20 uL) was added to each well and
Measurement: IC50 = 1952 nM (pChEMBL 5.710000038146973)
Descriptors: MW 367.41, ALogP 1.69, HBA 7, HBD 4, PSA 112.45, QED 0.46
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]nc(NCC3CCCOC3)c2cn1)c1ccccc1
InChIKey: XMPQVSFGUCVSFD-GICMACPYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 nL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-SFAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.5 nM hERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP.
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 394.48, ALogP 3.68, HBA 5, HBD 4, PSA 103.96, QED 0.51
Compound (SMILES): CO[C@H](C)C(=O)Nc1ccc(F)c([C@]23COC[C@H]2S(=O)(=O)C(C)(C)C(=N)N3)c1
InChIKey: HDZXDROMEIJJHI-MAZCYNQFSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: HTRF FRET Assay: This assay monitors the increase of 620 nm fluorescence that resulted from BACE1 cleavage of an APPswedish APPswe mutant peptide FRET substrate (QSY7-EISEVNLDAEFC-Europium-amide). This substrate contains an N-terminal QSY7 moiety that serves as a quencher of the C-terminal Europium fluorophore (620 nm Em). In the absence of enzyme activity, 620 nm fluorescence is low in the assay and increased linearly over 3 hours in the presence of uninhibited BACE1 enzyme Inhibition of BACE1 cleavage of the QSY7-APPswe-Eu substrate by inhibitors is manifested as a suppression of 620 nm fluorescence. Varying concentrations of inhibitors at 3× the final desired concentration in a volume of 10 ul are preincubated with purified human BACE1 catalytic domain (3 nM in 10 μl) for 30 minutes at 30° C. in reaction buffer containing 20 mM Na-Acetate pH 5.0, 10% glycerol, 0.1% Brij-35 and 7.5% DSMO. Reactions are initiated by addition of 10 μl of 600 nM QSY7-APPswe-Eu substrate (200 nM final) to give a final reaction volume of 30 μl in a 384 well Nunc HTRF plate. The reactions are incubated at 30° C. for 1.5 hours. The 620 nm fluorescence is then read on a Rubystar HTRF plate reader (BMG Labtechnologies) using a 50 millisecond delay followed by a 400 millisecond acquisition time window.
Measurement: Ki = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 413.47, ALogP 1.17, HBA 6, HBD 3, PSA 117.58, QED 0.68
Compound (SMILES): CO[C@H]1CC[C@H](c2cnc(N)c(-c3ccc(C(=O)N[C@H](CNC(C)=O)c4cccc(Cl)c4)c(F)c3)n2)CC1
InChIKey: CPFPYFWIIRGVIS-IUBQTAPSSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: ERK2 (20 pM) Kinase Assay: Compound potency against activated ERK2 was determined using a kinase assay that measures ERK2-catalyzed phosphorylation of biotinylated ERKtide peptide substrate ([Biotin]-AHA-K-R-E-L-V-E-P-L-T-P-S-G-E-A-P-N-Q-A-L-L-R-[NH2], the peptide sequence derived from EGF receptor: SEQ ID NO:1). The assay was carried out in 20 mM HEPES [pH 7.5], 5 mM MgCl2, 1 mM DTT, 0.01% Tween-20, 0.05% BSA using 0.02 nM ERK2, 400 nM ERKtide peptide and 35 uM ATP (all concentrations are final in the reaction) in a total volume of 10.25 uL. A 16-point, half-log dilution series of compounds at 41x final concentration was used for generating IC50 curves. Compound dilution series were prepared in 100% DMSO. ERK2 was preincubated with compounds for 30 minutes at ambient temperature. Reaction was initiated by addition of a substrate cocktail of ERKtide peptide and ATP and was allowed to proceed for 4 hours at ambient temperature. Reaction was terminated by addition of 10 uL of a 2x stop buffer consisting of 100 mM Tris-Cl [pH 7.5], 25 mM EDTA, 0.01% Tween 20, 20 ug/mL of AlphaScreen Protein A Acceptor Beads, 20 ug/mL of Streptavidin Donor Beads (PerkinElmer, Waltham, Mass.), and 1:1000 dilution phospho-EGF Receptor (Thr669) antibody (Cat #8808, Cell Signaling Technology, Danvers, Mass.). Terminated reactions were read, after overnight incubation in the dark, on an EnVision Multilabel Plate Reader (PerkinElmer, Waltham, Mass.), with excitation and emission wavelengths set to 680 nm and 570 nm, respectively. IC50 values were determined using a four-parameter fit.
Measurement: IC50 = 0.249 nM (pChEMBL 9.600000381469727)
Descriptors: MW 540.04, ALogP 4.8, HBA 6, HBD 3, PSA 119.23, QED 0.38
Compound (SMILES): CCn1c2c(c(=O)[nH]c1=O)C(c1ccc(C)cc1)C1=C(COC1=O)N2
InChIKey: MUOCQMZJLRQTRD-UHFFFAOYSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Inhibition of BI-BODIPY binding to BRDT bromodomain 1 (29 to 134 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) by fluorescence anisotropy assay
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 339.35, ALogP 1.23, HBA 6, HBD 2, PSA 93.19, QED 0.8
Compound (SMILES): CCCS(=O)(=O)Nc1cccc([C@@H](O)CNCCOc2ccc3c(C)n[nH]c3c2)c1
InChIKey: GYOBHFYHRWTYNA-NRFANRHFSA-N
Target: Beta-3 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P13945
Assay: Agonist activity at recombinant human beta3 adrenergic receptor expressed in CHO cells assessed as accumulation of cyclic AMP after 30 mins
Measurement: EC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 432.55, ALogP 2.73, HBA 6, HBD 4, PSA 116.34, QED 0.35
Compound (SMILES): CCOc1ccc(-c2ccc(Oc3ccccc3C(C)(C)C)c(NC(=O)Nc3ccc(C)cc3)c2)cc1C(=O)O
InChIKey: YULMFQUPWOBYBL-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: IDO Kynurenine Assay: Human IDO1/HEK293 cells were seeded at 10,000 cells per 50 uL per well with RPMI/phenol red free media contains 10% FBS in a 384-well black wall clear bottom tissue culture plate (Matrix Technologies LLC) 125 nL of certain concentration of compound was then added to each well using ECHO liquid handling systems. The cells were incubated for 20 hours in 37° C. incubator with 5% CO2.The compound treatments were stopped by adding Trichloroacetic Acid (Sigma-Aldrich) to a final concentration at 0.2%. The cell plate was further incubated at 50° C. for 30 minute. The equal volume supernatant (20 uL) and 0.2% (w/v) Ehrlich reagent (4-dimethylaminobenzaldehyde, Sigma-Aldrich) in glacial acetic acid were mixed in a new clear bottom 384-well plate. This plate was then incubated at room temperature for 30 minute. The absorbance at 490 nm was measured on Envision plate reader.Compound IC50 values were calculated using the counts of 500 nM of a reference standard treatment as one hundred percent inhibition, and counts of no compound but DMSO treatment as zero percent inhibition.
Measurement: IC50 = 1830 nM (pChEMBL 5.739999771118164)
Descriptors: MW 538.64, ALogP 8.49, HBA 4, HBD 3, PSA 96.89, QED 0.21
Compound (SMILES): N#Cc1cnc2ccc(F)cc2c1N1CCC(Oc2ccc(Cl)nc2)CC1
InChIKey: IIHJDLWVUCYZGC-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulation of human M4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization
Measurement: EC50 = 562.34 nM (pChEMBL 6.25)
Descriptors: MW 382.83, ALogP 4.34, HBA 5, HBD 0, PSA 62.04, QED 0.63
Compound (SMILES): O=C(NO)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(=O)Nc1ccccc1Cl
InChIKey: XESPWBKPCITCAE-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human HDAC4 using Boc-Lys(trifluoroacetyl)-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by trypsin-based fluorescence assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 514.65, ALogP 4.6, HBA 3, HBD 3, PSA 78.43, QED 0.27
Compound (SMILES): CC(C)(N)c1nc(-c2ccc(Cl)cc2)c[nH]1
InChIKey: ZFBHGYQVETXXBJ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of Cy3B-labeled ligand binding to recombinant human ERG expressed in HEK293 cells by fluorescence polarization method
Measurement: IC50 > 16000 nM (pChEMBL 4.796000003814697)
Descriptors: MW 235.72, ALogP 2.92, HBA 2, HBD 2, PSA 54.7, QED 0.84
Compound (SMILES): COC(=O)[C@]12CC[C@@H]([C@H](C)N)[C@@H]1[C@H]1CC[C@@H]3[C@@]4(C)CC[C@H](OC(C)=O)C(C)(C)[C@@H]4CC[C@@]3(C)[C@]1(C)CC2
InChIKey: BPAOPCJIWHFMFP-VTQIQSHQSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Competitive inhibition of equine serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition measured every 1 min for 30 mins by Dixon plot method
Measurement: Ki = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 515.78, ALogP 6.52, HBA 5, HBD 1, PSA 78.62, QED 0.43
Compound (SMILES): O=S(=O)(NCCN1CC=C(c2c[nH]c3ccc(Cl)cc23)CC1)c1cccc2ccccc12
InChIKey: UEDMFDWWGVDRAR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5-HT7 receptor expressed in CHO-K1 cell membranes after 120 mins by scintillation counting
Measurement: Ki = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 466.01, ALogP 5.04, HBA 3, HBD 2, PSA 65.2, QED 0.42
Compound (SMILES): COc1ccc(F)cc1[C@H]1C[C@@H]1CNCc1ccccc1Cl.Cl
InChIKey: GQHLQQKMSQROLY-PBCQUBLHSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in Flp-IN HEK293 cells assessed as induction of calcium flux measured every second for 5 mins by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 3548.13 nM (pChEMBL 5.449999809265137)
Descriptors: MW 319.81, ALogP 4.38, HBA 2, HBD 1, PSA 21.26, QED 0.85
Compound (SMILES): Cn1nccc1C(=O)NC[C@H]1OC[C@@](O)(CNC(=O)c2ccccc2)[C@@H]1O
InChIKey: OEBKZQVARQJFNM-RKVPGOIHSA-N
Target: Signal transduction protein TRAP (SINGLE PROTEIN), Staphylococcus aureus (strain Mu50 / ATCC 700699)
UniProt: Q7A2Q4
Assay: Inhibition of methicillin-resistant Staphylococcus aureus Mu50 TRAP assessed as potentiation of vancomycin-induced antibiofilm activity cotreated with vancomycin for 24 hrs
Measurement: EC50 = 23500 nM (pChEMBL 4.630000114440918)
Descriptors: MW 374.4, ALogP -0.93, HBA 7, HBD 4, PSA 125.71, QED 0.52
Compound (SMILES): c1cc2cc(c1)-c1cnc3ccc(nn13)NCCCCCO2
InChIKey: SUUOJCKRZPQUHP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 induced beta-catenin transcriptional activity in human HCT116 cells by luciferase reporter gene assay
Measurement: EC50 = 337 nM (pChEMBL 6.46999979019165)
Descriptors: MW 294.36, ALogP 3.37, HBA 5, HBD 1, PSA 51.45, QED 0.69
Compound (SMILES): COc1cc(-c2cc(F)cnc2OC)c(F)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12
InChIKey: SWKNAMZCGMPKQA-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells incubated for 3 to 5 mins at -125 mV holding potential by electrophysiology assay
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 524.51, ALogP 5.05, HBA 8, HBD 1, PSA 116.44, QED 0.31
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCC(=O)NCCCC[C@H](NC(=O)[C@@H](N)Cc2cnc[nH]2)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(N)=O)C(C)C
InChIKey: XHGRDYVFPGZPGA-YGCYTJROSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP1R expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by LANCE assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 3421.82
Compound (SMILES): CN(C)C(=O)Oc1cc(OC(=O)N(C)C)cc(C(O)CNC(C)(C)C#N)c1.Cl
InChIKey: FTCQNVKZNSGODB-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butyrylthiocholine iodide as substrate preincubated for 60 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 1133.33 nM (pChEMBL 5.949999809265137)
Descriptors: MW 378.43, ALogP 1.73, HBA 7, HBD 2, PSA 115.13, QED 0.77
Compound (SMILES): O=C(c1ccc(Nc2nc3ccccc3n3nnnc23)cc1)N1CCN(c2ccccn2)CC1
InChIKey: OPTAHTMJJWYVIB-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of TNKS1 (unknown origin) expressed in HEK293 cells co-expressing TCF/LEF luciferase plasmid assessed as reduction in wnt3a ligand-induced Wnt-dependent increase in beta-catenin preincubated for 1 hr followed by wnt3a ligand stimulation for 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 451.49, ALogP 2.77, HBA 9, HBD 1, PSA 104.44, QED 0.44
Compound (SMILES): O=c1[nH]c2ccc(-n3cnnc3)cc2c(=O)n1O
InChIKey: PJHQDQUSOJNNGW-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 445 nM (pChEMBL 6.349999904632568)
Descriptors: MW 245.2, ALogP -0.49, HBA 7, HBD 2, PSA 105.8, QED 0.56
Compound (SMILES): CN(C)CCCNc1cc2nc3n(c(=O)c2cc1F)CC/C3=C\c1ccc(OCc2ccccc2)cc1O
InChIKey: FPZLTQHJJZMUIR-PXLXIMEGSA-N
Target: Nucleoside diphosphate kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: P22392
Assay: Binding affinity to NM23-H2 H118F mutant (unknown origin) by SPR analysis
Measurement: Kd = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 514.6, ALogP 5.13, HBA 7, HBD 2, PSA 79.62, QED 0.3
Compound (SMILES): O=C(NO)c1ccc(CN2c3ccccc3S(=O)(=O)C[C@H]3CCCC[C@H]32)cc1
InChIKey: DMIDPYMXHVUIIM-QZTJIDSGSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 400.5, ALogP 3.16, HBA 5, HBD 2, PSA 86.71, QED 0.61
Compound (SMILES): CC1(C(=O)N2CC[C@@H](c3nc(-c4ccc(C(=O)Nc5cc(C(F)(F)F)ccn5)cc4)c4c(N)nccn34)C2)COC1
InChIKey: NSJMTJKYDCNXPE-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC assessed as reduction in anti-IgM-induced MIP1beta
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 565.56, ALogP 4, HBA 8, HBD 2, PSA 127.74, QED 0.37
Compound (SMILES): CN1C(=O)C2=C(C1=O)N(CC(=O)Nc1ccc(-c3cccnc3)nn1)CCC2
InChIKey: HXLGDTLTDGOORD-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 378.39, ALogP 0.83, HBA 7, HBD 1, PSA 108.39, QED 0.78