lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): c1ccc(OCC2CC2)c(CCn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)c1
InChIKey: SVUJKKUKCQKMKG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 386.46, ALogP 3.76, HBA 6, HBD 1, PSA 81.51, QED 0.5
Compound (SMILES): CC[C@H](C)[C@@H]1C(=O)O[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)NCc1ccccc1)C(C)C)C(C)C
InChIKey: FXAMLICIOFJBJL-RKFFNLMFSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human Jurkat cell lysate using Suc-LLVY-AMC as substrate pretreated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 459.59, ALogP 2.17, HBA 5, HBD 3, PSA 113.6, QED 0.44
Compound (SMILES): CN(C)c1ccc(-c2cn(CC(=O)N[C@H]3[C@H]([C@H](O)[C@H](O)CO)OC(C(=O)O)=C[C@@H]3O)nn2)cc1
InChIKey: KFFPNNIJIGOPQI-MZCHELMPSA-N
Target: Sialidase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WWR8
Assay: Inhibition of MBP-fused human NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 36000 nM (pChEMBL 4.440000057220459)
Descriptors: MW 477.47, ALogP -2.06, HBA 11, HBD 6, PSA 190.5, QED 0.23
Compound (SMILES): O=C(c1cn(CCN2CCOCC2)c2ccc(O)cc12)C1CCCCC1
InChIKey: FVQYDNJMRKXPES-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at N-terminal HA-tagged human CB2 receptor expressed in HEK293 cells transfected with YFP-Epac-RLuc assessed as decrease in forskolin-stimulated cAMP level by BRET assay
Measurement: EC50 = 18.6 nM (pChEMBL 7.730000019073486)
Descriptors: MW 356.47, ALogP 3.44, HBA 5, HBD 1, PSA 54.7, QED 0.83
Compound (SMILES): Nc1oc2c(-c3cc(Cl)cc(Cl)c3)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: CDIOTLFFDHTDCL-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 422.67, ALogP 6.92, HBA 4, HBD 2, PSA 64.08, QED 0.38
Compound (SMILES): COc1ccc(Br)cc1C(=O)Nc1ccccc1
InChIKey: RGXLZUOJOVUHAT-UHFFFAOYSA-N
Target: Thiosulfate sulfurtransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16762
Assay: Inhibition of refolded rhodanese (unknown origin) preincubated with Escherichia coli GroEL/GroES for 60 mins in absence of compound followed by compound addition by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 306.16, ALogP 3.71, HBA 2, HBD 1, PSA 38.33, QED 0.94
Compound (SMILES): O=c1[nH]c2ccc(C3=NN=C(NCc4ccccc4)SC3)cc2[nH]1
InChIKey: PNJQHHXWPZEHTA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of DYRK1A (unknown origin) at 1 uM by kinomescan method
Measurement: IC50 = 9410 nM (pChEMBL 5.03000020980835)
Descriptors: MW 337.41, ALogP 2.45, HBA 5, HBD 3, PSA 85.4, QED 0.69
Compound (SMILES): NS(=O)(=O)c1cc(NC(=O)c2ccccc2)c(OC(=O)c2ccccc2)c([N+](=O)[O-])c1
InChIKey: JUMLIGNXGODMQQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of carbonic anhydrase 9 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 441.42, ALogP 2.71, HBA 7, HBD 2, PSA 158.7, QED 0.26
Compound (SMILES): CCOc1cc2c(Nc3ccc(F)c(Cl)c3)c(N)oc2c(-c2ccccc2)n1
InChIKey: IFWVLGPLNBTTFN-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 397.84, ALogP 6.01, HBA 5, HBD 2, PSA 73.31, QED 0.43
Compound (SMILES): Clc1cccc(Cn2cnc(-c3cc4[nH]nnc4cn3)c2)c1
InChIKey: WLHOJGUAXPKUMX-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PHF8 expressed in baculovirus infected Sf9 cells using H3K9mel-biotin labelled peptide as substrate measured after 15 mins by Lance TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 310.75, ALogP 2.92, HBA 5, HBD 1, PSA 72.28, QED 0.63
Compound (SMILES): COCC1c2c(-c3ccncc3)c(-c3cccc(C)n3)nn2CC1(C)C
InChIKey: RUUMQGIGKGSSDJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of mouse ABL expressed in Sf9 insect cells using GGEAIYAAPFKK as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 348.45, ALogP 4.09, HBA 5, HBD 0, PSA 52.83, QED 0.71
Compound (SMILES): Cc1nn(-c2cc(C(=O)O)ccn2)c(O)c1C
InChIKey: ZTSZMVPLKHSHGA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 233.23, ALogP 1.29, HBA 5, HBD 2, PSA 88.24, QED 0.82
Compound (SMILES): Cc1c(C(=O)NCCCN(C)C)cn2ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c12
InChIKey: LKHBLJXMYCTBJQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using poly (Glu, Tyr) 4:1 as substrate after 1 hr by ELISA
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 591.62, ALogP 4.15, HBA 8, HBD 3, PSA 129.96, QED 0.18
Compound (SMILES): FC(F)(F)CNc1nc(Nc2ccnc(C(F)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: PLCJHAPDBYLXRZ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 483.3, ALogP 5.08, HBA 7, HBD 2, PSA 88.51, QED 0.49
Compound (SMILES): O=C(CCCN1CCN(c2cccc(Cl)c2Cl)CC1)c1cc2c3c(c1)CCN3C(=O)CC2
InChIKey: SMCWUBAJDPUTDT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserine from serotonin 5-HT2A receptor in rat brain cortex homogenates incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 37.8 nM (pChEMBL 7.420000076293945)
Descriptors: MW 472.42, ALogP 4.61, HBA 4, HBD 0, PSA 43.86, QED 0.58
Compound (SMILES): C[C@@H](Nc1nc(N[C@H]2CCC[C@H]2O)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: UHUHOBBXPQIHRY-SCDSUCTJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 408.43, ALogP 3.49, HBA 7, HBD 3, PSA 95.85, QED 0.67
Compound (SMILES): CCOC(=O)c1c(-c2ccccc2C)[nH]c2c1cc(O)c1ccccc12
InChIKey: GPALORVAXDXFEO-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES-1 in microsomal membranes isolated from IL-1beta-stimulated human A549 cells preincubated for 15 mins followed by PGH2 addition measured after 1 mins by RP-HPLC analysis
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 345.4, ALogP 5.18, HBA 3, HBD 2, PSA 62.32, QED 0.5
Compound (SMILES): O=C(c1ccc(-c2ccc3[nH]ccc3c2)s1)c1cc(F)c(F)c(O)c1F
InChIKey: PDZDSJHULKVPPZ-UHFFFAOYSA-N
Target: Estradiol 17-beta-dehydrogenase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P51658
Assay: Inhibition of mouse microsomal fraction 17beta-HSD2 using [3H]-E2 as substrate after 20 mins in presence of NAD+ by radio-flow detector based analysis
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 373.36, ALogP 5.25, HBA 3, HBD 2, PSA 53.09, QED 0.38
Compound (SMILES): COCC1(c2ccc(-c3c(-c4cc(C(=O)O)ccn4)ncn3C)cc2)CC1
InChIKey: IGZZKOJEHRREEV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 363.42, ALogP 3.53, HBA 5, HBD 1, PSA 77.24, QED 0.72
Compound (SMILES): CCCCCc1cc2c(c(OS(=O)(=O)c3ccc(C)cc3)c1)[C@@H]1[C@H](O)C(C)=CC[C@H]1C(C)(C)O2
InChIKey: DRUFUMSJTHQNCK-AVPJRLCVSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from recombinant human full length CB2 receptor expressed in HEK293 cell membranes after 90 mins by topcount method
Measurement: IC50 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 484.66, ALogP 6.08, HBA 5, HBD 1, PSA 72.83, QED 0.29
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1)C(=O)O
InChIKey: OVEVKHHIEURDIP-RKDXNWHRSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C) Inhibitors: A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 396.37, ALogP 3.05, HBA 7, HBD 3, PSA 112.92, QED 0.65
Compound (SMILES): Fc1ccc(Cn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)c(F)c1
InChIKey: LABVGZXSSYPADP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 406.32, ALogP 4.08, HBA 5, HBD 1, PSA 72.28, QED 0.52
Compound (SMILES): Cc1cnn2c(NCc3ccc[n+]([O-])c3)cc(N3CCCC[C@@H]3CCO)nc12
InChIKey: BYUAPXZEZUYLJI-QGZVFWFLSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of recombinant CDK5 (unknown origin) expressed in Sf9 cells using histone H1 derived biotinylated peptide and 33P-ATP incubated for 1 hr by liquid scintillation counting method
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 382.47, ALogP 2.02, HBA 7, HBD 2, PSA 92.63, QED 0.5
Compound (SMILES): COc1cc(OC)cc(C(=O)Nc2cc(-c3ccncc3)c[nH]c2=O)c1
InChIKey: MYGPNOIWNUFXSX-UHFFFAOYSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQS7
Assay: Inhibition of human full length N-terminal GST-tagged Aurora B (1 to 344 end residues)/His-tagged INCENP (803 to 918 end residues) expressed in baculovirus expression system using fluorescence-labeled FL-Peptide 21 as substrate after 60 mins in presence of ATP by fluorescence assay based Cheng-Prusoff equation analysis
Measurement: Ki = 32900 nM (pChEMBL 4.480000019073486)
Descriptors: MW 351.36, ALogP 2.71, HBA 5, HBD 2, PSA 93.31, QED 0.74
Compound (SMILES): Cc1[nH]nc(N)c1-c1cccc(Cl)c1
InChIKey: HOORSUWNFBFXET-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged NIK (M1 to P947 residues) expressed in Sf9 insect cells using AKDVDQGSLCTSFVGTLQY peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 207.66, ALogP 2.62, HBA 2, HBD 2, PSA 54.7, QED 0.76
Compound (SMILES): NS(=O)(=O)c1ccc(O)c(NC(=O)NCCc2ccccc2)c1
InChIKey: PPIDDTTURUJDTG-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 231.4 nM (pChEMBL 6.639999866485596)
Descriptors: MW 335.39, ALogP 1.4, HBA 4, HBD 4, PSA 121.52, QED 0.62
Compound (SMILES): CCc1ccc(C2c3[nH]c4ccccc4c3C(=O)CN2c2ncc(-c3ccc(OC)c(OC)c3)cn2)o1
InChIKey: MXRCTQYKTXQWTH-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of full length recombinant human N-terminal GST-tagged PDE11A4 expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 = 634 nM (pChEMBL 6.199999809265137)
Descriptors: MW 494.55, ALogP 5.59, HBA 7, HBD 1, PSA 93.48, QED 0.33
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(C)=O)C(=O)NCc1cn([C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C)C(=O)N[C@H](CCCNC(=N)N)C(N)=O)nn1
InChIKey: IVXVAQIIVMKYGT-FBTQSVADSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Reversible competitive inhibition of human cathepsin K using fluorogenic AMC-derived peptide substrate assessed as reduction in residual activity preincubated for 30 mins followed by substrate addition
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 1615.85
Compound (SMILES): O=c1cc(Sc2ccc(-c3ccc(O)cc3)cc2)[nH]c(=O)n1O
InChIKey: MBXVAZICFZAFMX-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 328.35, ALogP 2.3, HBA 6, HBD 3, PSA 95.32, QED 0.51
Compound (SMILES): Cc1c(OCC(O)CO)cn2ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c12
InChIKey: AEAOPPHJQXFHPG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using poly (Glu, Tyr) 4:1 as substrate after 1 hr by ELISA
Measurement: IC50 = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 553.52, ALogP 3.2, HBA 9, HBD 4, PSA 147.31, QED 0.22
Compound (SMILES): CCn1c(=O)c(=O)[nH]c2cc(C(=O)N(C)Cc3cnn(-c4ccccc4)c3)ccc21
InChIKey: WOECCYJDFDPEPV-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to human partial length BRPF1 (E627 to G740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay
Measurement: Kd = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 403.44, ALogP 2.17, HBA 6, HBD 1, PSA 92.99, QED 0.52
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C(=O)Nc3ccc(F)cc3F)cc2)cc1
InChIKey: RRCSJXJNTIZFGN-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Transrepression of RORgammat in anti-CD3/CD28 stimulated human PBMC derived CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by measuring reduction in IL-17A level after 7 days by flow cytometry analysis
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 500.57, ALogP 4.86, HBA 4, HBD 2, PSA 92.34, QED 0.46
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)Cc1ccc(F)cc1
InChIKey: XBGIGBHCVFRAGP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 354.39, ALogP 2.91, HBA 5, HBD 1, PSA 71.25, QED 0.71
Compound (SMILES): c1ccc(Oc2ccccc2CCn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)cc1
InChIKey: BQEFHNXDQSRGAO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 408.47, ALogP 4.77, HBA 6, HBD 1, PSA 81.51, QED 0.42
Compound (SMILES): Cn1c(=O)c2cc(S(=O)(=O)NC3(C#N)CC3)ccc2n(C)c1=O
InChIKey: GSLXEMUKIRRVQR-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 4960 nM (pChEMBL 5.300000190734863)
Descriptors: MW 334.36, ALogP -0.43, HBA 7, HBD 1, PSA 113.96, QED 0.82
Compound (SMILES): CC(C)C(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: OAHACOXPLGQGIK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.42, ALogP 4.99, HBA 5, HBD 1, PSA 72.28, QED 0.5
Compound (SMILES): O=C(Nc1cccc(Cl)c1)c1cccc(Br)c1O
InChIKey: LJTQVIFOJANPHH-UHFFFAOYSA-N
Target: Thiosulfate sulfurtransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16762
Assay: Inhibition of refolded rhodanese (unknown origin) preincubated with Escherichia coli GroEL/GroES for 60 mins in absence of compound followed by compound addition by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 326.58, ALogP 4.06, HBA 2, HBD 2, PSA 49.33, QED 0.87
Compound (SMILES): Cc1ccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: LVTPIPCJSJQBGO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 398.39, ALogP 4.3, HBA 5, HBD 1, PSA 72.28, QED 0.54
Compound (SMILES): CC(Oc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1)c1ccccc1
InChIKey: GBJNSFXBUOTPIV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 449.89, ALogP 5.34, HBA 6, HBD 1, PSA 86.47, QED 0.39
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)c(=O)n(C(C)C)c3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)c1
InChIKey: LDDDGIHXYBWEAR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR kinase domain (unknown origin) expressed using baculovirus expression system incubated for 1 hr using Poly(Glu,Tyr) 4:1 by ELISA method
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 570.65, ALogP 3.15, HBA 11, HBD 2, PSA 126.62, QED 0.24
Compound (SMILES): CCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCc3cccc(Cl)c3)cc2)n(CCC)c1=O
InChIKey: LACDZBUEWBNRRO-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-602 from human adenosine A2B receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 593.13, ALogP 3.98, HBA 9, HBD 1, PSA 103.39, QED 0.27
Compound (SMILES): O=c1cc(Sc2cccc(-c3ccc(F)cc3)c2)[nH]c(=O)n1O
InChIKey: OARQEMCHUOOBCU-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 > 140 nM (pChEMBL 6.854000091552734)
Descriptors: MW 330.34, ALogP 2.73, HBA 5, HBD 2, PSA 75.09, QED 0.57
Compound (SMILES): O=C(NCc1ccc(OC(F)(F)F)c(Cl)c1)c1ccc(S(=O)(=O)Nc2ncns2)c(F)c1
InChIKey: FXTBLDWXLZMPPV-UHFFFAOYSA-N
Target: Sodium channel protein type 2 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q99250
Assay: Inhibition of human NaV1.2
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 510.88, ALogP 3.96, HBA 7, HBD 2, PSA 110.28, QED 0.47
Compound (SMILES): CC(C)(CN1C(=O)c2cccc3cccc(c23)C1=O)C[N+](C)(C)CCCCCCCCCC[N+](C)(C)CC#CCOC1=NOCC1.[Br-].[Br-]
InChIKey: NGZDNRJEFKSLOD-UHFFFAOYSA-L
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate pretreated for 4.5 mins followed by substrate addition and measured after 2.5 mins by Ellman's method
Measurement: IC50 = 263.03 nM (pChEMBL 6.579999923706055)
Descriptors: MW 632.89, ALogP 6.49, HBA 5, HBD 0, PSA 68.2, QED 0.09
Compound (SMILES): Cc1cc(OCc2nc3ccccc3s2)ccc1NC(=O)Nc1ccc(Cl)c(Cl)c1
InChIKey: FGXLEECGXSDIMM-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of recombinant human sEH preincubated for 10 mins followed by PHOME substrate addition and measured after 60 mins by fluorescence-based assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 458.37, ALogP 7.13, HBA 4, HBD 2, PSA 63.25, QED 0.33
Compound (SMILES): OC1(c2ccc(Cl)c(C(F)(F)F)c2)CCN(CCCN(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: FOLXSEMOHDUPCN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]LSD from human 5-HT2B receptor expressed in HEK cells by radioligand binding assay
Measurement: Ki = 177 nM (pChEMBL 6.75)
Descriptors: MW 524.96, ALogP 7.15, HBA 3, HBD 1, PSA 26.71, QED 0.33
Compound (SMILES): O=C(O)c1ccnc(-c2cn(Cc3cccc(-c4ccccc4)c3)cn2)c1
InChIKey: IGXZIIVCDBVBSB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 355.4, ALogP 4.36, HBA 4, HBD 1, PSA 68.01, QED 0.58
Compound (SMILES): CC[N+](CC)(CC)CCCCOc1ccc(/C=C/c2ccccc2)cc1.[I-]
InChIKey: CAKFDDIAFHTZIJ-WPDLWGESSA-M
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Antagonist activity at human alpha9alpha10 nACHR expressed in xenopous laevis oocyte assessed as inhibition of ACh-induced channel current after 5 mins at -70 mV holding potential by two electrode voltage clamp method
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 352.54, ALogP 5.89, HBA 1, HBD 0, PSA 9.23, QED 0.28
Compound (SMILES): NS(=O)(=O)c1cc(NC(=O)Nc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c(O)c([N+](=O)[O-])c1
InChIKey: YRXZSSWEDACJGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of carbonic anhydrase 12 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 488.32, ALogP 3.63, HBA 6, HBD 4, PSA 164.66, QED 0.22
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(F)cc2/C=C/c2ccc(F)cc2)c1
InChIKey: MFXLJRSRCQXMLR-DAFODLJHSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 433.41, ALogP 4.99, HBA 5, HBD 1, PSA 77.24, QED 0.42
Compound (SMILES): N#Cc1cc(Nc2nc(NC3CC(F)(F)C3)nc(-n3ccc(C(F)(F)F)n3)n2)ccn1
InChIKey: UDPIYDLIPGHOFT-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 437.34, ALogP 3.3, HBA 9, HBD 2, PSA 117.23, QED 0.58
Compound (SMILES): CCc1ccc(NC(=O)Nc2cc(S(N)(=O)=O)ccc2O)cc1
InChIKey: SDMONTDKVXKVIJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 57.8 nM (pChEMBL 7.239999771118164)
Descriptors: MW 335.39, ALogP 2.25, HBA 4, HBD 4, PSA 121.52, QED 0.64
Compound (SMILES): Fc1cc(F)cc(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: PEKCODXRCQZWOA-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 486.4, ALogP 5.96, HBA 6, HBD 2, PSA 75.62, QED 0.43
Compound (SMILES): COc1cc2c(cc1O)CN(CCCCNC(=O)c1ccc(Br)cc1)CC2
InChIKey: ZKVLCVQFJYHODC-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-Methylspiperone from human dopamine D4 receptor expressed in HEK cell membranes
Measurement: Ki = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 433.35, ALogP 3.73, HBA 4, HBD 2, PSA 61.8, QED 0.65
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OC2CCc3cc(F)ccc32)c1
InChIKey: ZPFAMOBPFNYKFI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 339.33, ALogP 3.17, HBA 5, HBD 1, PSA 77.24, QED 0.79
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](Cc1ccc(CP(=O)(O)O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: AGUANHCNVQFXGF-IMNFJDCFSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from N-terminal His-tagged human recombinant XIAP BIR3 (253 to 347 residues) expressed in Escherichia coli BL21(DE3) Gold after 1 hr by DELFIA
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 587.61, ALogP 0.2, HBA 6, HBD 6, PSA 191.16, QED 0.18
Compound (SMILES): FC(F)(F)c1cccc(-c2nc(NC3CCC3)nc(NC3CCC3)n2)n1
InChIKey: PVIJXHIYMYVGOF-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 364.38, ALogP 3.88, HBA 6, HBD 2, PSA 75.62, QED 0.84
Compound (SMILES): CNc1cc(Nc2c(F)c(F)cc(F)c2F)nn2c(C(=O)NC[C@](C)(O)CO)cnc12
InChIKey: HNSFAKGAIZARCR-SFHVURJKSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Displacement of [3H]-c-AMP from His-Tb-tagged human PDE4D2 (86 to 413 residues) preincubated for 10 mins followed by [3H]-c-AMP addition measured after 1 hr by scintillation proximity assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 442.37, ALogP 1.54, HBA 8, HBD 5, PSA 123.81, QED 0.28
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(-c3ccc(CN4CCOCC4)cc3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: GDFZQTWVTPRZJP-OYDLWJJNSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) using 5'-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 477.65, ALogP 5.01, HBA 7, HBD 2, PSA 75.44, QED 0.48
Compound (SMILES): CC(Cn1cnc(-c2cc(C(=O)O)ccn2)c1)N1CCCC1
InChIKey: AXQRVZDNIHSEAN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 300.36, ALogP 2.13, HBA 5, HBD 1, PSA 71.25, QED 0.92
Compound (SMILES): CCCCN1C(=O)[C@H]2Cc3c([nH]c4ccccc34)[C@@H](c3ccc(CC)s3)N2C1=O
InChIKey: MHKSTLAWFJQTLC-WIYYLYMNSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of recombinant human N-terminal GST-tagged PDE3B (592 to end residues) expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 407.54, ALogP 4.87, HBA 3, HBD 1, PSA 56.41, QED 0.61
Compound (SMILES): CCc1cc2c(Nc3ccc(F)c(Cl)c3)c(N)oc2c(-c2ccccc2)n1
InChIKey: GLENMCKMNRZFCT-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 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 381.84, ALogP 6.18, HBA 4, HBD 2, PSA 64.08, QED 0.44
Compound (SMILES): Cc1ccc2oc(-c3ccc(OCCOCCOCCn4cc(CN(CCOc5ccc6c(=O)cc(-c7ccccc7)oc6c5)Cc5ccccc5)nn4)cc3)cc(=O)c2c1
InChIKey: OYXBXNPLVSLBAG-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 818.93, ALogP 8.33, HBA 12, HBD 0, PSA 131.29, QED 0.07
Compound (SMILES): Fc1ccccc1CCn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: JCPHXPGNGSEBCP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 uM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 uM sodium L-ascorbate, 5 uM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen Streptavidin-coated Donor beads, and AlphaScreen Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 ug/ml beads.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 402.36, ALogP 4.13, HBA 5, HBD 1, PSA 72.28, QED 0.51
Compound (SMILES): C[C@@]12CSC(=N1)c1csc(n1)CNC(=O)C[C@@H](/C=C/CCS)OC(=O)[C@H](CCCCNC(=O)O[C@@H]1CC/C=C/CCC1)NC2=O
InChIKey: LUPYACIUYLGDJP-ATRICVITSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of C-terminal His-tagged full length recombinant human HDAC8 expressed in baculovirus infected Sf9 insect cells using HDAC class 2a substrate 1 after 30 mins by fluorescence assay
Measurement: IC50 = 1115 nM (pChEMBL 5.949999809265137)
Descriptors: MW 677.92, ALogP 4.47, HBA 11, HBD 4, PSA 148.08, QED 0.13
Compound (SMILES): O=c1cc(-c2ccc(OCCCc3cn(CCOCCOCCOc4ccc(-c5cc(=O)c6cc(F)ccc6o5)cc4)nn3)cc2)oc2cc(F)ccc12
InChIKey: YQFDTJKOMAIUKG-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 735.74, ALogP 7.23, HBA 11, HBD 0, PSA 128.05, QED 0.09