lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC#CCOc1nc(-c2ncccn2)nc(NS(=O)(=O)c2ccccc2)c1Oc1ccccc1OC
InChIKey: FQUDOIORVYSHBU-UHFFFAOYSA-N
Target: Endothelin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25101
Assay: Antagonist activity against human ET-1 by ELISA analysis
Measurement: IC50 = 4.33 nM (pChEMBL 8.359999656677246)
Descriptors: MW 503.54, ALogP 3.94, HBA 9, HBD 1, PSA 125.42, QED 0.34
Compound (SMILES): Cc1ccc(Nc2nc(-c3ccc([N+](=O)[O-])cc3)nc3sc4c(c23)CCCC4)cc1
InChIKey: NTJGLGFVEIFCOX-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 416.51, ALogP 6.2, HBA 6, HBD 1, PSA 80.95, QED 0.32
Compound (SMILES): CSc1nn(-c2ccccc2C)c(-c2ccc3c(c2)OCCO3)c1-n1ccnc1
InChIKey: YXASBEJNAWAXMU-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of C-terminal Hexahistidine-tagged human recombinant IDH1 R132C mutant expressed in Escherichia coli BL21 (DE3) cells assessed as NADPH consumption in presence of alpha KG incubated for 1 hr by MST assay
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 404.5, ALogP 4.53, HBA 7, HBD 0, PSA 54.1, QED 0.47
Compound (SMILES): Cc1nc(-c2ccc(F)cc2)ccc1NC(=O)Nc1ccccc1S(N)(=O)=O
InChIKey: IQFVFKPDFKRNAT-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to human CA1 assessed as inhibition constant incubated for 6 hrs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 400.44, ALogP 3.49, HBA 4, HBD 3, PSA 114.18, QED 0.62
Compound (SMILES): Clc1ccc(-c2nc(Nc3ccc(Br)cc3)c3c4c(sc3n2)CCCC4)cc1
InChIKey: WOKXKJBTSMQRHT-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA
Measurement: IC50 = 9120 nM (pChEMBL 5.039999961853027)
Descriptors: MW 470.82, ALogP 7.4, HBA 4, HBD 1, PSA 37.81, QED 0.34
Compound (SMILES): COc1ccccc1Oc1c(NS(C)(=O)=O)nc(-c2ncccn2)nc1OCC1CCCCN1C
InChIKey: NHOBXXVUIZLOKT-UHFFFAOYSA-N
Target: Endothelin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25101
Assay: Antagonist activity against human ET-1 by ELISA analysis
Measurement: IC50 = 2.21 nM (pChEMBL 8.65999984741211)
Descriptors: MW 500.58, ALogP 2.97, HBA 10, HBD 1, PSA 128.66, QED 0.47
Compound (SMILES): CC(C)CN(c1ccc(-c2ccc(CC(=O)O)cc2)cc1)S(=O)(=O)c1c(Cl)cccc1Cl
InChIKey: HPXMIIADFRZAMT-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR LBD (unknown origin) using fluorescein-SRC2-2 as substrate incubated for 3 hrs by TR-FRET assay
Measurement: EC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 492.42, ALogP 6.14, HBA 3, HBD 1, PSA 74.68, QED 0.41
Compound (SMILES): CC(C)Cn1c(C(=O)NCCCNC(=O)n2cc(F)c(=O)[nH]c2=O)cc2cc(C(F)(F)F)ccc21
InChIKey: GKDZSGOSTQSGNT-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant full length his tagged C-terminal SARS-CoV 2 main protease (M1 to Q307 residues) expressed in Escherichia coli BL21 (DE3) cells using LGSAVLQ-Rh110-dP as peptide substrate preincubated for 1 hr followed by substrate addition and measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 497.45, ALogP 2.68, HBA 6, HBD 3, PSA 117.99, QED 0.34
Compound (SMILES): Cn1cccc1-c1ccc2ncnc(Nc3ccc4scnc4c3)c2c1
InChIKey: ZGSRGMUNQNJRJN-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of N-terminal polyHis-tagged human RIPK2 (8 to 310 residues) expressed in Sf9 cells using MBP as substrate preincubated for 15 mins followed by ATP addition measured after 90 mins by ADP-Glo assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 357.44, ALogP 4.99, HBA 6, HBD 1, PSA 55.63, QED 0.49
Compound (SMILES): COc1ccc(-c2nc(-c3ccccc3O)n(-c3ccc(S(C)(=O)=O)cc3)n2)c(O)c1
InChIKey: NMRMXZMCFILQRR-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of recombinant ovine COX-2 using arachidonic acid as substrate preincubated with compound for 5 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 437.48, ALogP 3.42, HBA 8, HBD 2, PSA 114.54, QED 0.49
Compound (SMILES): CN1CCN(c2nc(N)nc(C(C)(C)Oc3ccccc3Cl)n2)CC1
InChIKey: KJEOOSAJFDVYPE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Binding affinity to human 5HT6 receptor expressed in HEK293 cells assessed as inhibition constant incubated for 1 hr radioligand binding assay
Measurement: Ki = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 362.87, ALogP 2.17, HBA 7, HBD 1, PSA 80.4, QED 0.89
Compound (SMILES): C=CC(=O)Nc1cccc(C)c1Nc1cc2c(cn1)cc(-c1c(Cl)c(OC)cc(OC)c1Cl)c(=O)n2CCCO
InChIKey: HOECHMGENDGVGF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) kinase activity
Measurement: IC50 = 25.94 nM (pChEMBL 7.590000152587891)
Descriptors: MW 583.47, ALogP 5.95, HBA 8, HBD 3, PSA 114.71, QED 0.2
Compound (SMILES): COc1ccccc1Oc1c(NS(C)(=O)=O)nc(-c2ncccn2)nc1OCC1CCCC1
InChIKey: MMMQGMZYQKVNJQ-UHFFFAOYSA-N
Target: Endothelin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25101
Assay: Antagonist activity against human ET-1 by ELISA analysis
Measurement: IC50 = 2.19 nM (pChEMBL 8.65999984741211)
Descriptors: MW 471.54, ALogP 3.68, HBA 9, HBD 1, PSA 125.42, QED 0.5
Compound (SMILES): Cc1ccc(Nc2ncnc3cnc(/C=C/c4ccc(Cl)cc4)cc23)cn1
InChIKey: GDANGPXOFKSTJT-WEVVVXLNSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human recombinant RIPK1 using MBP as substrate preincubated for 15 mins followed by substrate addition and measured after 120 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 373.85, ALogP 5.3, HBA 5, HBD 1, PSA 63.59, QED 0.53
Compound (SMILES): NC(=O)c1cccc2[nH]c(NC(=O)c3cccc(C(=O)N4CCC(Nc5ncc(F)cn5)CC4)c3)nc12
InChIKey: BTXUKBPFPHAMAC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) in presence of ATP by kinase-glo plus luminescent assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 502.51, ALogP 2.56, HBA 7, HBD 4, PSA 158.99, QED 0.32
Compound (SMILES): FC(F)(F)c1ncccc1Sc1cnc2[nH]c(NC3CCCNC3)nc2n1
InChIKey: RRIWJMYEKCKAGE-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of wild type SHP2 (unknown origin) assessed as dephosphorylation of DIFMUP by fluorescence based envision microplate reader analysis
Measurement: IC50 = 1726 nM (pChEMBL 5.760000228881836)
Descriptors: MW 395.41, ALogP 3.08, HBA 7, HBD 3, PSA 91.41, QED 0.63
Compound (SMILES): OC[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC(C4CCCCC4)C4CCCCC4)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: GGRCFWIZJSTQIM-YZSDQEEOSA-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 assessed as inhibition constant incubated for 1 hr
Measurement: Ki = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 490.05, ALogP 3.7, HBA 8, HBD 4, PSA 116.32, QED 0.46
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(Nc2ccc(CN3CCN(S(=O)(=O)N(C)C)CC3)cc2)c(C#N)cc1Cl
InChIKey: COZLWRNUCNUPTQ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild type HIV-1 reverse transcriptase assessed as inhibition of biotin-dUTP incorporation using ABTS as substrate incubated for 1 hrs by ELISA analysis
Measurement: IC50 = 686 nM (pChEMBL 6.159999847412109)
Descriptors: MW 580.11, ALogP 4.56, HBA 8, HBD 1, PSA 125.59, QED 0.41
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(Nc2ccc(CN3CCN(S(C)(=O)=O)CC3)cc2)c(C#N)cc1F
InChIKey: YOEBJQFRMNROGH-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild type HIV-1 reverse transcriptase assessed as inhibition of biotin-dUTP incorporation using ABTS as substrate incubated for 1 hrs by ELISA analysis
Measurement: IC50 = 294 nM (pChEMBL 6.53000020980835)
Descriptors: MW 534.62, ALogP 4.19, HBA 8, HBD 1, PSA 122.35, QED 0.48
Compound (SMILES): Clc1ccc(-c2nc(Nc3cccc(Br)c3)c3c4c(sc3n2)CCCC4)cc1
InChIKey: OXJPLAYXLITPHK-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA
Measurement: IC50 = 8550 nM (pChEMBL 5.070000171661377)
Descriptors: MW 470.82, ALogP 7.4, HBA 4, HBD 1, PSA 37.81, QED 0.34
Compound (SMILES): CC(C)CN(c1ccc(-c2ccc(OCC(=O)O)c(F)c2)cc1)S(=O)(=O)C1CCCCC1
InChIKey: AFJDFXURRULSQV-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR LBD (unknown origin) using fluorescein-SRC2-2 as substrate incubated for 3 hrs by TR-FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 463.57, ALogP 5.08, HBA 4, HBD 1, PSA 83.91, QED 0.56
Compound (SMILES): Cc1ccc2c(c1CCC(=O)NCCCCCC(=O)Nc1ccccc1N)C(=O)C(=O)C(C(C)C)=C2
InChIKey: CELIALHZILFHSH-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of full length C-terminal his6-tagged human recombinant HDAC1 (1 to 482 residues) expressed in Sf9 cells using trypsin and Ac-peptide as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 60 mins
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 489.62, ALogP 4.63, HBA 5, HBD 3, PSA 118.36, QED 0.24
Compound (SMILES): COC(=O)c1ccc(CCCCn2cc(Cn3cc(C)c(N)nc3=O)nn2)cc1
InChIKey: ONBVSENKKPQDEZ-UHFFFAOYSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of p300 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 396.45, ALogP 1.58, HBA 9, HBD 1, PSA 117.92, QED 0.45
Compound (SMILES): CN1C(=O)c2ccc(OS(=O)(=O)c3cccc4ccccc34)cc2OC1(C)C
InChIKey: HWAMELDQAJHDBI-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human recombinant Cannabinoid receptor 2 by GTPgammaS binding assay
Measurement: EC50 = 2951.21 nM (pChEMBL 5.53000020980835)
Descriptors: MW 397.45, ALogP 3.81, HBA 5, HBD 0, PSA 72.91, QED 0.63
Compound (SMILES): CCOc1cccc2c(Nc3ccc(N(C)C)cc3)c3ccccc3nc12
InChIKey: MXIZPEVUYQXIGS-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant LSD1 ( unknown origin) expressed in Escherichia coli BL21 (DE3) cells using H3K4me2 peptide as substrate incubated for 30 mins in presence of FAD by fluorescence microplate reader analysis
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 357.46, ALogP 5.6, HBA 4, HBD 1, PSA 37.39, QED 0.47
Compound (SMILES): COc1cc(-c2n[nH]c3ncc(-c4ccc(N)nc4)cc23)cc(OC)c1OC
InChIKey: BYODDABQBNBRRN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of human ABL1 in presence of ATP by microplate reader analysis
Measurement: IC50 = 38.3 nM (pChEMBL 7.420000076293945)
Descriptors: MW 377.4, ALogP 3.29, HBA 7, HBD 2, PSA 108.17, QED 0.55
Compound (SMILES): CN(C)c1cnn2ccc(N3CC4CCCC4C3)nc12
InChIKey: XAEISXOYDFWUIX-UHFFFAOYSA-N
Target: Sphingomyelin phosphodiesterase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY59
Assay: Inhibition of recombinant human nSMase2 using SM as substrate incubated for 1 hr by fluorescence assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 271.37, ALogP 2.03, HBA 5, HBD 0, PSA 36.67, QED 0.84
Compound (SMILES): Cc1ccc(NC(=O)COc2ccc(N3C(=O)CSC3c3ccc(Cl)cc3)cc2)cc1
InChIKey: QAFUUTFADOEEAQ-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX-2
Measurement: IC50 = 16710 nM (pChEMBL 4.78000020980835)
Descriptors: MW 452.96, ALogP 5.44, HBA 4, HBD 1, PSA 58.64, QED 0.54
Compound (SMILES): Cn1c(C(=O)NCCCNC(=O)n2cc(F)c(=O)[nH]c2=O)cc2ccccc21
InChIKey: BTOVWCZBXBSAQA-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant full length his tagged C-terminal SARS-CoV 2 main protease (M1 to Q307 residues) expressed in Escherichia coli BL21 (DE3) cells using LGSAVLQ-Rh110-dP as peptide substrate preincubated for 1 hr followed by substrate addition and measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 387.37, ALogP 0.55, HBA 6, HBD 3, PSA 117.99, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2CCC(C(=O)N/N=C3\C(=O)N(Cc4ccccc4)c4ccccc43)CC2)cc1
InChIKey: WPWSLANCDUENHS-MXNGAVTRSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 574.66, ALogP 2.05, HBA 7, HBD 3, PSA 154.27, QED 0.35
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(-n3nnnc3-c3c(OC)c(OC)cc4ccccc34)cc1)CC2
InChIKey: TVRQHXCXLWJHOB-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of MDR1 (unknown origin) overexpressed in MDCK cells using Calcein-AM as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by fluorescence based assay
Measurement: EC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 551.65, ALogP 5.12, HBA 9, HBD 0, PSA 83.76, QED 0.25
Compound (SMILES): CN(C)c1cnn2ccc(N3CCC(O)CC3)nc12
InChIKey: PSNVZCSYUSNXJM-UHFFFAOYSA-N
Target: Sphingomyelin phosphodiesterase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY59
Assay: Inhibition of recombinant human nSMase2 using SM as substrate incubated for 1 hr by fluorescence assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 261.33, ALogP 0.76, HBA 6, HBD 1, PSA 56.9, QED 0.86
Compound (SMILES): Nc1nc2c(ncn2[C@H]2CC[C@@](O)(CP(=O)([O-])O)C2)c(=O)[nH]1.[Na+]
InChIKey: HPCSYAHTGDEYMF-BJUCTQDSSA-M
Target: IMP-specific 5'-nucleotidase 1 (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: A0A144A134
Assay: Binding affinity to recombinant Plasmodium falciparum 3D7 ISN1 assessed as dissociation constant by thermophoresis analysis
Measurement: Kd = 24100 nM (pChEMBL 4.619999885559082)
Descriptors: MW 329.25, ALogP -0.66, HBA 7, HBD 5, PSA 167.35, QED 0.46
Compound (SMILES): O=C(Cc1ccccc1)N[C@H](Cc1ccccc1)C(=O)C(=O)NCc1ccccn1
InChIKey: OQUAYXBTSNWMCV-OAQYLSRUSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 main protease by FRET assay
Measurement: IC50 = 219.4 nM (pChEMBL 6.659999847412109)
Descriptors: MW 401.47, ALogP 2.24, HBA 4, HBD 2, PSA 88.16, QED 0.54
Compound (SMILES): CC(C)(C#N)c1ccc2c(c1)N(C(=O)C1CCc3ccccc3CC1)Cc1cccnc1N2
InChIKey: BTTKTSNRFDGVEO-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: R132H IDH1 Enzymatic Assay: Each test compound (10 mM stock in DMSO) is diluted in DMSO to make a 10-point, 3-fold dilution series. 125 nL of each dilution or DMSO alone is dispensed to a 384-well Greiner Lumitrac 200 assay plate using an Echo® Liquid Handler. To each well of the plate is added 20 uL of enzyme in assay buffer or assay buffer alone. Assay buffer consists of 50 mM sodium phosphate, pH 7.0, 50 mM magnesium chloride, 50 mM sodium chloride, and 0.01% (w/v) bovine serum albumin. When present, the R132H mutant IDH1 enzyme is at a working concentration of 1.875 nM (final concentration in assay of 1.5 nM). The assay plate is allowed to incubate for 30 minutes at room temperature and 5 uL of 5× substrate mixture (2.5 uM nicotinamide adenine dinucleotide phosphate, 100 uM adenosine diphosphate, 7.5 mM glyceraldehyde-3-phosphate, 7.5 ug/mL of spinach glyceraldehyde-3-phosphate dehydrogenase, 25 nM phosphoglycerate kinase, and 5 mM alpha-ketoglutarate in assay buffer) is added to all wells. The reaction plate is incubated for 60 minutes followed by addition of 25 uL of Promega Kinase-GLO reagent to all wells and 10-minute incubation.Luminescence is measured using a PerkinElmer Envision plate reader. The percent activity of each dilution is determined as the ratio of background corrected signal to the background corrected signal of wells receiving only DMSO. IC50 values are determined by fitting percent activity data to a four-parameter logistic dose response equation. The IC50 values of the exemplified compounds are included in the tables above in Examples section.Using the above biological assay, all compounds in the examples have IC50 of about 1 nM to about 40,000 nM, or more specifically, about 1 nM to about 20,000 nM, or even more specifically, about 5 nM to about 15,000 nM, or even more specifically, about 5 nM to about 10,000 nM, or even more specifically, about 5 nM to about 5,000 nM, or still more specifically, about 5 nM to about 1,000 nM. Such a result is indicative of the intrinsic activity of the compounds in use as an inhibitor of a mutant IDH1 enzyme. Specific IC50 activity data for the exemplified compounds disclosed herein is provided in the following table.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 436.56, ALogP 5.67, HBA 4, HBD 1, PSA 69.02, QED 0.53
Compound (SMILES): O=C(Nc1ccc(Oc2nc(Cl)nc3ccccc23)cc1)c1cccnc1
InChIKey: MSGVEATXZLQCQR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR-2 incubated for 1 hr by ELISA analysis
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 376.8, ALogP 4.72, HBA 5, HBD 1, PSA 77, QED 0.52
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(-n3nnc(-c4c(OC)c(OC)cc5ccccc45)n3)cc1)CC2
InChIKey: UGYIQNNFZACMFA-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of MDR1 (unknown origin) overexpressed in MDCK cells using Calcein-AM as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by fluorescence based assay
Measurement: EC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 551.65, ALogP 5.12, HBA 9, HBD 0, PSA 83.76, QED 0.25
Compound (SMILES): COc1ccc2c3c([nH]c2c1)[C@H](CC(C)C)N1C(=O)[C@H](CCC(=O)N2CCOCC2)NC(=O)[C@@H]1C3
InChIKey: UTPUVICBEMOLDT-BVSLBCMMSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 in human A549 cells assessed as increase in PPIX level preincubated for ALA for 4 hrs followed by compound addition and measured after 2 hrs by UPLC-QTOFMS analysis
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 482.58, ALogP 2.15, HBA 5, HBD 2, PSA 103.97, QED 0.66
Compound (SMILES): c1ccc(-c2ccc3ncnc(Nc4ccc5scnc5c4)c3c2)cc1
InChIKey: UUUWVKHLQTUXIV-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of N-terminal polyHis-tagged human RIPK2 (8 to 310 residues) expressed in Sf9 cells using MBP as substrate preincubated for 15 mins followed by ATP addition measured after 90 mins by ADP-Glo assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 354.44, ALogP 5.65, HBA 5, HBD 1, PSA 50.7, QED 0.45
Compound (SMILES): COc1cccc2c1CN(C(=O)c1ccc(O)c(C(=O)N3Cc4ccc(OCCCN(C)C)cc4C3)c1)C2
InChIKey: STYCKXLVQBVRNZ-UHFFFAOYSA-N
Target: Heat shock protein 75 kDa, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q12931
Assay: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay
Measurement: Kd = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 515.61, ALogP 4.04, HBA 6, HBD 1, PSA 82.55, QED 0.46
Compound (SMILES): COc1cc2c(cn1)N(C)C(=O)C(C(=O)Nc1ncc(Cc3ccccc3)s1)CC2
InChIKey: CWVBFSQTTNHODF-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIPK1 assessed as inhibition constant by ADP-Glo Kinase assay
Measurement: Ki = 52.48 nM (pChEMBL 7.28000020980835)
Descriptors: MW 422.51, ALogP 3.3, HBA 6, HBD 1, PSA 84.42, QED 0.64
Compound (SMILES): c1cnc2c(N3CCCC3)cnn2c1
InChIKey: MUNIAEZFZFZAJQ-UHFFFAOYSA-N
Target: Sphingomyelin phosphodiesterase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY59
Assay: Inhibition of recombinant human nSMase2 using SM as substrate incubated for 1 hr by fluorescence assay
Measurement: IC50 = 13400 nM (pChEMBL 4.869999885559082)
Descriptors: MW 188.23, ALogP 1.33, HBA 4, HBD 0, PSA 33.43, QED 0.68
Compound (SMILES): CC(C)CN(c1ccc(-c2ccc(OCC(=O)O)cc2)cc1)S(=O)(=O)c1c(Cl)cccc1Cl
InChIKey: DFTUISBHSROJNM-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR LBD (unknown origin) using fluorescein-SRC2-2 as substrate incubated for 3 hrs by TR-FRET assay
Measurement: EC50 = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 508.42, ALogP 5.98, HBA 4, HBD 1, PSA 83.91, QED 0.38
Compound (SMILES): Nc1nc2c(ncn2[C@H]2C[C@@H]3OP(=O)(O)/C=C/[C@H]4O[C@@H](n5cnc6c(N)ncnc65)C[C@@H]4OP(=O)(O)OC[C@H]3O2)c(=O)[nH]1
InChIKey: FSPVJYISCQDUSC-ASRWSEBTSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at STING R232 mutant (unknown origin) expressed in digitonin -permeabilized HEK293T cells preincubated for 30 mins followed by washout and measured after 5 hrs by Bright-glo luciferase assay
Measurement: EC50 = 10790 nM (pChEMBL 4.96999979019165)
Descriptors: MW 638.43, ALogP 0.3, HBA 17, HBD 5, PSA 279.96, QED 0.18
Compound (SMILES): COc1ccc(-c2nc(-c3ccc(OC)cc3O)n(-c3ccc(S(N)(=O)=O)cc3)n2)c(O)c1
InChIKey: AQFWRJPHIFNXGM-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of recombinant ovine COX-2 using arachidonic acid as substrate preincubated with compound for 5 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 468.49, ALogP 2.68, HBA 9, HBD 3, PSA 149.79, QED 0.39
Compound (SMILES): COc1cc(OC)cc(-c2cc3cnc(Nc4c(C)cccc4N4CCOCC4)cc3n(CCCO)c2=O)c1
InChIKey: LOZDDUHVOZJGMT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) kinase activity
Measurement: IC50 = 16.43 nM (pChEMBL 7.78000020980835)
Descriptors: MW 530.63, ALogP 4.35, HBA 9, HBD 2, PSA 98.08, QED 0.33
Compound (SMILES): O=C(NCc1ccccn1)C(=O)[C@@H](Cc1ccccc1)NC(=O)[C@H]1COCCN1C(=O)C1CCC(F)(F)CC1
InChIKey: SPHHADSVJQMGAP-DHIUTWEWSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 main protease by FRET assay
Measurement: IC50 = 14.6 nM (pChEMBL 7.840000152587891)
Descriptors: MW 542.58, ALogP 2.05, HBA 6, HBD 2, PSA 117.7, QED 0.47
Compound (SMILES): N=C(N)c1ccc2cc(OC(=O)c3cc4ccccc4sc3=O)ccc2c1
InChIKey: LWNJXBYOZLFQQB-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of beta-FXIIa in human plasma using S-2302 as substrate incubated for 10 mins by chromogenic assay
Measurement: Ki = 2230 nM (pChEMBL 5.650000095367432)
Descriptors: MW 374.42, ALogP 3.92, HBA 5, HBD 2, PSA 93.24, QED 0.25
Compound (SMILES): COC1(CCN)CN(c2nc3nc(Sc4cccnc4C(F)(F)F)cnc3[nH]2)C1
InChIKey: DAAHDAPCWWQWGS-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of wild type SHP2 (unknown origin) assessed as dephosphorylation of DIFMUP by fluorescence based envision microplate reader analysis
Measurement: IC50 = 2269 nM (pChEMBL 5.639999866485596)
Descriptors: MW 425.44, ALogP 2.47, HBA 8, HBD 2, PSA 105.84, QED 0.62
Compound (SMILES): C[C@H](NC(=O)C(c1cccnc1)N(C(=O)C#CC(C)(C)C)c1ccc(-c2ccccc2)cc1)c1ccccc1
InChIKey: NHYPDBAMPIURIJ-HKIGIVDHSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of MPro of SARS CoV-2 BetaCoV/Wuhan/WIV04/2019 preincubated for 30 mins followed by substrate addition measured for 1 hr by FRET assay
Measurement: IC50 = 2510 nM (pChEMBL 5.599999904632568)
Descriptors: MW 515.66, ALogP 6.75, HBA 3, HBD 1, PSA 62.3, QED 0.28
Compound (SMILES): CN(C)c1cnn2ccc(N3CCOCC3)nc12
InChIKey: JOXWMNJMLFTCMT-UHFFFAOYSA-N
Target: Sphingomyelin phosphodiesterase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY59
Assay: Inhibition of recombinant human nSMase2 using SM as substrate incubated for 1 hr by fluorescence assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 247.3, ALogP 0.63, HBA 6, HBD 0, PSA 45.9, QED 0.78
Compound (SMILES): CC(=O)Oc1ccccc1-c1nc(-c2ccccc2OC(C)=O)n(-c2ccccc2)n1
InChIKey: JWWGGBWQSGMAFA-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of recombinant ovine COX-2 using arachidonic acid as substrate preincubated with compound for 5 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.43, ALogP 4.45, HBA 7, HBD 0, PSA 83.31, QED 0.36
Compound (SMILES): CC(C)c1onc(-c2c(Cl)cccc2Cl)c1C(=O)n1ccc2c(/C=C/C(=O)O)cccc21
InChIKey: KADGEUCPGOYAHO-MDZDMXLPSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibitory Activity Against IDH1R132H and IDH1R132C Enzymes: The IDH1R132H protein and the IDH1R132C protein were prepared as follows: the IDH1R132H or IDH1R132C gene was integrated into a pET24b(+) vector (Novagen) to prepare a construct for C-terminal fusion of 6× histidine tag. After transformation of Rosetta 2 (DE3) E. coli, the expression of the protein was induced with IPTG. The E. coli was collected and homogenized, followed by the affinity purification of the 6× histidine fusion protein using HisTrap HP columns (GE Healthcare Japan Corp.) and gel filtration purification using Superdex 200 columns (GE Healthcare Japan Corp.) to obtain the IDH1R132H or IDH1R132C protein of interest.IDH1R132H and IDH1R132C each convert 2-oxoglutarate and NADPH to D-2-hydroxyglutarate (2-HG) and NADP+. Therefore, the activity of the IDH1R132H and IDH1R132C enzymes can be measured by detecting NADPH levels.The enzyme inhibitory activity evaluation was carried out as follows: 40 μL each of reaction solutions containing different concentrations of each compound (100 mM Tris-HCl (pH 7.5), 150 mM NaCl, 20 mM MgCl2, 0.5 mg/mL bovine serum albumin, 1 mM reduced glutathione, 40 μM NADPH, 0.5 mM 2-oxoglutarate, 0.5% dimethyl sulfoxide, 50000 to 0.128 nM compound, and 12 nM IDH1R132H or 10 nM IDH1R132C as the enzyme) was added to each well of 384-well plates (Greiner Bio One International GmbH, #781096) and incubated at room temperature. While NADPH-derived fluorescence was occasionally monitored, the reaction was terminated by the addition of 5 μL of 0.5 M EDTA before consumption of NADPH. 5 μL of WST-8 reagent (Dojindo Laboratories, #CK04) was further added and mixed therewith. 15 minutes later, the absorbance at 450 nm was measured using a plate reader (PerkinElmer, Inc., EnVision). The observed absorbance value reflects the amount of residual NADPH. From the absorbance data, the enzyme inhibitory activity of each compound at each concentration was calculated and analyzed using medical statistical analysis software GraphPad Prism to calculate an IC50 value.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 469.32, ALogP 6.51, HBA 5, HBD 1, PSA 85.33, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2CCC(C(=O)N/N=C3\C(=O)Nc4ccccc43)CC2)cc1
InChIKey: KNQCGQSDVMQVBA-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 62.4 nM (pChEMBL 7.210000038146973)
Descriptors: MW 484.54, ALogP 0.46, HBA 7, HBD 4, PSA 163.06, QED 0.44
Compound (SMILES): C=CC(=O)NCCCn1c(=O)c(-c2c(Cl)c(OC)cc(OC)c2Cl)cc2cnc(Nc3c(C)cccc3NC(=O)C=C)cc21
InChIKey: ZWQWTVLDLQPTSW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) kinase activity
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 636.54, ALogP 6.26, HBA 8, HBD 3, PSA 123.58, QED 0.12
Compound (SMILES): N#CC1(Nc2ccc3ccccc3c2)CCN(CCc2ccc(S(N)(=O)=O)cc2)CC1
InChIKey: AZGQGKCMEUZXLX-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human CA-I incubated for 15 mins by stop-flow method
Measurement: Ki = 377.9 nM (pChEMBL 6.420000076293945)
Descriptors: MW 434.57, ALogP 3.5, HBA 5, HBD 2, PSA 99.22, QED 0.62
Compound (SMILES): COCCOc1cc2ncnc(Nc3cccc(OS(=O)(=O)F)c3)c2cc1OCCOC
InChIKey: DFSDQJWWAXBBHO-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate preincubated for 10 mins followed by substrate addition and measured after 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 467.48, ALogP 3.02, HBA 10, HBD 1, PSA 118.1, QED 0.31
Compound (SMILES): CCC(Sc1cc(Cl)ccc1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: IHJUENPGSBRDEB-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured after 5 mins by Ellman's method
Measurement: IC50 = 12100 nM (pChEMBL 4.920000076293945)
Descriptors: MW 413.38, ALogP 3.76, HBA 7, HBD 1, PSA 71.17, QED 0.75
Compound (SMILES): COc1cc(CN(CCCCc2ccccc2)C(=O)NC(C)(C)C(=O)O)cc(OC)c1C
InChIKey: ADVSJMPPTFSREI-UHFFFAOYSA-N
Target: Lysophosphatidic acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92633
Assay: Antagonist activity at human LPA1 receptor stably expressed in rat RH7777 cells assessed as reduction in LPA-induced intracellular Ca2+ concentration preincubated for 30 mins followed by LPA addition measured by Fluo-4 probe based fluorescence assay
Measurement: IC50 = 2140 nM (pChEMBL 5.670000076293945)
Descriptors: MW 442.56, ALogP 4.41, HBA 4, HBD 2, PSA 88.1, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2CCC(C(=O)N/N=C3\C(=O)Nc4ccc(F)cc43)CC2)cc1
InChIKey: RNZANDGTVGBACZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 35.5 nM (pChEMBL 7.449999809265137)
Descriptors: MW 502.53, ALogP 0.6, HBA 7, HBD 4, PSA 163.06, QED 0.42
Compound (SMILES): O=C(c1ccc(O)c(-n2ccc3ccccc32)c1)N1Cc2ccccc2C1
InChIKey: LVXPGPGVNRZSOH-UHFFFAOYSA-N
Target: Heat shock protein 75 kDa, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q12931
Assay: Binding affinity to TRAP1 (unknown origin) assessed as dissociation constant incubated for 24 hrs by fluorescence polarization assay
Measurement: Kd = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 354.41, ALogP 4.49, HBA 3, HBD 1, PSA 45.47, QED 0.58
Compound (SMILES): CC(C)Cc1ccc(C(C)C(=O)NCc2ccc(-n3[se]c4ccccc4c3=O)cc2)cc1
InChIKey: VUTWXUJTLHGWPF-UHFFFAOYSA-N
Target: Thioredoxin reductase 1, cytoplasmic (SINGLE PROTEIN), Rattus norvegicus
UniProt: O89049
Assay: Inhibition of rat TrxR1 using DTNB as substrate preincubated for 15 mins followed by substrate addition and measured for 20 mins by colorimetric method
Measurement: EC50 = 17200 nM (pChEMBL 4.760000228881836)
Descriptors: MW 491.49
Compound (SMILES): CC1CN(C(=O)c2cc(Cc3n[nH]c(=O)c4ccccc34)ccc2F)Cc2nnc(CN(C)C)n21
InChIKey: REZQZHZAWVOQLT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin) incubated for 1 hr by ELISA analysis
Measurement: IC50 = 17.6 nM (pChEMBL 7.75)
Descriptors: MW 475.53, ALogP 2.52, HBA 7, HBD 1, PSA 100.01, QED 0.48
Compound (SMILES): C#CC(=O)N(c1ccc(-c2ccccc2)cc1)[C@H](C(=O)N[C@@H](C)c1ccccc1)c1cccnc1
InChIKey: STZSMNMPHCLEPA-ZTOMLWHTSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of MPro of SARS CoV-2 BetaCoV/Wuhan/WIV04/2019 preincubated for 30 mins followed by substrate addition measured for 1 hr by FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 459.55, ALogP 5.33, HBA 3, HBD 1, PSA 62.3, QED 0.38
Compound (SMILES): Clc1ccc(Cn2cc(CNC3CCCCCC3)nn2)cc1
InChIKey: GHHFSGQWXBMGLW-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured every 1 min for 20 mins by spectrophotometric analysis
Measurement: IC50 = 607 nM (pChEMBL 6.21999979019165)
Descriptors: MW 318.85, ALogP 3.79, HBA 4, HBD 1, PSA 42.74, QED 0.85
Compound (SMILES): CC(C)C[C@@H]([C@H](O)C[C@H](O)C#C[C@@H](C)C[C@H](C)C[C@@H](C)COCc1ccccc1)[C@@H](O)c1cc(O)cc(O)c1
InChIKey: UIORGDFBMQIBGF-JLFRGFGUSA-N
Target: L-2,3-diaminopropanoate--citrate ligase (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325 / PS 47)
UniProt: Q2G1M9
Assay: Inhibition of Staphylococcus aureus SbnE incubated for 1 hr by malachite green staining based microplate reader analysis
Measurement: IC50 = 11850 nM (pChEMBL 4.929999828338623)
Descriptors: MW 540.74, ALogP 5.81, HBA 6, HBD 5, PSA 110.38, QED 0.18
Compound (SMILES): COCCOc1cc2ncnc(Nc3ccc(F)c(OS(=O)(=O)F)c3)c2cc1OCCOC
InChIKey: SFRLKESDBYWSQW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged recombinant human EGFR (668 to end residues) expressed in baculovirus infected Sf9 cells incubated for 1 hrs in presence of ATP by ADP-Glo reagent based assay
Measurement: IC50 = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 485.47, ALogP 3.16, HBA 10, HBD 1, PSA 118.1, QED 0.3
Compound (SMILES): C=CC(=O)N1CCC(c2onc(-c3c(Cl)cccc3Cl)c2C(=O)n2ccc3c(/C=C/C(=O)O)cccc32)CC1
InChIKey: WRWLWJJKRVPXGR-MDZDMXLPSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of human wild type IDH1 R132C mutant expressed in Escherichia coli BL21 (DE3) cells incubated for 60 mins by fluorescence based analysis
Measurement: IC50 = 0.44 nM (pChEMBL 9.359999656677246)
Descriptors: MW 564.43, ALogP 6.28, HBA 6, HBD 1, PSA 105.64, QED 0.28
Compound (SMILES): COc1ccc2cc(C(=O)Oc3ccc4cc(C(=N)N)ccc4c3)c(=O)oc2c1
InChIKey: MYDAOLARMWSMRJ-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of beta-FXIIa in human plasma using S-2302 as substrate incubated for 10 mins by chromogenic assay
Measurement: Ki = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 388.38, ALogP 3.46, HBA 6, HBD 2, PSA 115.61, QED 0.18
Compound (SMILES): Cc1ccsc1-c1ccc2ncnc(Nc3ccc4scnc4c3)c2c1
InChIKey: XTCHKTGNNBBKHW-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of N-terminal polyHis-tagged human RIPK2 (8 to 310 residues) expressed in Sf9 cells using MBP as substrate preincubated for 15 mins followed by ATP addition measured after 90 mins by ADP-Glo assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 374.49, ALogP 6.02, HBA 6, HBD 1, PSA 50.7, QED 0.42
Compound (SMILES): CCCCCCNC(=O)[C@H](CCC(=O)O)NC(=O)Cc1ccc(Cl)cc1
InChIKey: GNBDZCBXWSUAPE-INIZCTEOSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) by fluorescence based assay
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 382.89, ALogP 2.93, HBA 3, HBD 3, PSA 95.5, QED 0.48
Compound (SMILES): CC(C)CN(c1ccc(-c2cccc(C(=O)O)c2)cc1)S(=O)(=O)c1c(Cl)cccc1Cl
InChIKey: SAEMVSWPALABOM-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR LBD (unknown origin) using fluorescein-SRC2-2 as substrate incubated for 3 hrs by TR-FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 478.4, ALogP 6.21, HBA 3, HBD 1, PSA 74.68, QED 0.44
Compound (SMILES): CN(C)c1ccc(Nc2c3ccccc3nc3c(-c4ccccc4)cccc23)cc1
InChIKey: DFBKAWWWSABIJH-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant LSD1 ( unknown origin) expressed in Escherichia coli BL21 (DE3) cells using H3K4me2 peptide as substrate incubated for 30 mins in presence of FAD by fluorescence microplate reader analysis
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 389.5, ALogP 6.86, HBA 3, HBD 1, PSA 28.16, QED 0.34
Compound (SMILES): C#Cc1cc(C=O)cc(Nc2ncnc3cc(OCCOC)c(OCCOC)cc23)c1
InChIKey: JGYUWRRSTZEWGH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged recombinant human EGFR (668 to end residues) expressed in baculovirus infected Sf9 cells incubated for 1 hrs in presence of ATP by ADP-Glo reagent based assay
Measurement: IC50 = 109.8 nM (pChEMBL 6.960000038146973)
Descriptors: MW 421.45, ALogP 3.22, HBA 8, HBD 1, PSA 91.8, QED 0.29
Compound (SMILES): NCc1ccc(NC(=O)c2ccc3c(N4CCC(N)CC4)ncnc3c2)cc1
InChIKey: NGRZYOOEQKEARV-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Displacement of 3H-SAM from PRMT1 (unknown origin) using biotinylated-histone H4 peptide as substrate incubated for 45 mins by SPA assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 376.46, ALogP 2.27, HBA 6, HBD 3, PSA 110.16, QED 0.64
Compound (SMILES): CN1C(=O)C(C(=O)Nc2cn(Cc3ccccc3)cn2)CCc2ccncc21
InChIKey: OUNRZJOLEXJQGR-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIPK1 assessed as inhibition constant by ADP-Glo Kinase assay
Measurement: Ki = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 375.43, ALogP 2.49, HBA 5, HBD 1, PSA 80.12, QED 0.71
Compound (SMILES): CC(C)CN(c1ccc(-c2ccc(OCC(=O)O)c(F)c2)cc1)S(=O)(=O)c1c(Cl)cccc1Cl
InChIKey: NRHZDVWFLPAECO-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR LBD (unknown origin) using fluorescein-SRC2-2 as substrate incubated for 3 hrs by TR-FRET assay
Measurement: EC50 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 526.41, ALogP 6.11, HBA 4, HBD 1, PSA 83.91, QED 0.36
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2CCCC(C(=O)N/N=C3\C(=O)Nc4cc(Cl)ccc43)C2)cc1
InChIKey: QADFUKFAEDDBKO-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 115.6 nM (pChEMBL 6.940000057220459)
Descriptors: MW 518.98, ALogP 1.11, HBA 7, HBD 4, PSA 163.06, QED 0.42
Compound (SMILES): NCc1ccc(Nc2ncnc3cc(C(=O)NC4CCNCC4)ccc23)cc1
InChIKey: OSFMOYPGDKHZCZ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SMYD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H7B4
Assay: Displacement of 3H-SAM from SMYD3 (unknown origin) using biotinylated-MAP3K2 as substrate incubated for 45 mins by SPA assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 376.46, ALogP 2.31, HBA 6, HBD 4, PSA 104.96, QED 0.54
Compound (SMILES): Ic1nc(N[C@H](C2CCC2)C2CC2)c2nc[nH]c2n1
InChIKey: LBXYASBAVRSXCB-SECBINFHSA-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 assessed as inhibition constant incubated for 1 hr
Measurement: Ki = 313 nM (pChEMBL 6.5)
Descriptors: MW 369.21, ALogP 2.95, HBA 4, HBD 2, PSA 66.49, QED 0.64
Compound (SMILES): O=C(CNS(=O)(=O)c1ccc2ccccc2c1)c1ccccc1
InChIKey: ZVGSMMBQCIHOJW-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Inhibition of recombinant human KAT6A catalytic domain using [3H]-acetyl-coA as substrate pretreated with compound for 20 mins followed by substrate addition and measured after 4 hrs by liquid scintillation counter analysis
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 325.39, ALogP 3, HBA 3, HBD 1, PSA 63.24, QED 0.73
Compound (SMILES): C=CS(=O)(=O)N(c1ccc(-c2ccccc2)cc1)[C@H](C(=O)N[C@@H](C)c1ccccc1)c1cccnc1
InChIKey: HZCACNUXNXZZCO-DWACAAAGSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of MPro of SARS CoV-2 BetaCoV/Wuhan/WIV04/2019 preincubated for 30 mins followed by substrate addition measured for 1 hr by FRET assay
Measurement: IC50 = 6490 nM (pChEMBL 5.190000057220459)
Descriptors: MW 497.62, ALogP 5.65, HBA 4, HBD 1, PSA 79.37, QED 0.32
Compound (SMILES): COc1cccc(-c2nc(-c3ccccc3O)n(-c3ccc(S(N)(=O)=O)cc3)n2)c1O
InChIKey: PQZIBLSDHLPWNU-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 using arachidonic acid as substrate preincubated with compound for 5 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 = 20030 nM (pChEMBL 4.699999809265137)
Descriptors: MW 438.47, ALogP 2.67, HBA 8, HBD 3, PSA 140.56, QED 0.43
Compound (SMILES): O=C(CCCCCC(=O)Nc1cc(-c2ccc3ncn(Cc4ccccc4F)c3c2)[nH]n1)NO
InChIKey: XIOFYKZOYJTYRW-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 ITD mutant using EAIYAAPFAKKK as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 120 mins by filter-binding method relative to control
Measurement: IC50 = 92.3 nM (pChEMBL 7.039999961853027)
Descriptors: MW 464.5, ALogP 4.01, HBA 6, HBD 4, PSA 124.93, QED 0.16
Compound (SMILES): CC(C)CN(C(=O)c1c(Cl)cccc1Cl)c1ccc(-c2ccc(OCC(=O)O)c(F)c2)cc1
InChIKey: IUUQEYWJNFBFOG-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR LBD (unknown origin) using fluorescein-SRC2-2 as substrate incubated for 3 hrs by TR-FRET assay
Measurement: EC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 490.36, ALogP 6.57, HBA 3, HBD 1, PSA 66.84, QED 0.39
Compound (SMILES): CCOc1nc2c(cc1C(=O)Nc1cccc(-c3ccn(C)n3)n1)CC(C)(C)O2
InChIKey: HMLYLDYFOBSOTG-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) using FAM-labeled peptide as substrate incubated for 10 mins in presence of ATP by mobility shift assay
Measurement: IC50 = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 393.45, ALogP 3.24, HBA 7, HBD 1, PSA 91.16, QED 0.72
Compound (SMILES): Clc1cc2ncnc(Nc3ccc4scnc4c3)c2cc1-c1cc[nH]n1
InChIKey: FAKYWDLIOSDCID-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of N-terminal polyHis-tagged human RIPK2 (8 to 310 residues) expressed in Sf9 cells using MBP as substrate preincubated for 15 mins followed by ATP addition measured after 90 mins by ADP-Glo assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 378.85, ALogP 5.03, HBA 6, HBD 2, PSA 79.38, QED 0.46
Compound (SMILES): CC(C)c1ccc(Cn2cc(CNC34CC5CC(CC(C5)C3)C4)nn2)cc1
InChIKey: ZDVRRRLMNGMWIW-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured every 1 min for 20 mins by spectrophotometric analysis
Measurement: IC50 = 799 nM (pChEMBL 6.099999904632568)
Descriptors: MW 364.54, ALogP 4.51, HBA 4, HBD 1, PSA 42.74, QED 0.82
Compound (SMILES): CN(C)C(=O)c1ccc(Nc2c3ccccc3nc3ccccc23)cc1
InChIKey: GWNVUMGNWBKCFJ-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant LSD1 ( unknown origin) expressed in Escherichia coli BL21 (DE3) cells using H3K4me2 peptide as substrate incubated for 30 mins in presence of FAD by fluorescence microplate reader analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 341.41, ALogP 4.83, HBA 3, HBD 1, PSA 45.23, QED 0.54
Compound (SMILES): O=C(COc1ccc(N2C(=O)CSC2c2ccc(Cl)cc2)cc1)Nc1ccccc1
InChIKey: UPASJXPBJWSOGT-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX-2
Measurement: IC50 = 5860 nM (pChEMBL 5.230000019073486)
Descriptors: MW 438.94, ALogP 5.14, HBA 4, HBD 1, PSA 58.64, QED 0.58
Compound (SMILES): CC1CCCn2ccc(=O)c3ccc(nc32)-n2c(=O)[nH]c3nccc(c32)O1
InChIKey: ISPCMJYEMFDPOQ-UHFFFAOYSA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKC theta (unknown origin) in presence of ATP at Km
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 363.38, ALogP 1.98, HBA 7, HBD 1, PSA 94.8, QED 0.52
Compound (SMILES): CC(=O)/C=C/C(=O)N(c1ccc(-c2ccccc2)cc1)C(C(=O)N[C@@H](C)c1ccccc1)c1cccnc1
InChIKey: CPZXNZDMAPZSGH-NTLASXOJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of MPro of SARS CoV-2 BetaCoV/Wuhan/WIV04/2019 preincubated for 30 mins followed by substrate addition measured for 1 hr by FRET assay
Measurement: IC50 = 17050 nM (pChEMBL 4.769999980926514)
Descriptors: MW 503.6, ALogP 5.85, HBA 4, HBD 1, PSA 79.37, QED 0.29
Compound (SMILES): Cc1cc(Cc2ccc(F)c(C(=O)N3Cc4nnc(-c5ccccn5)n4C(C)C3)c2)n[nH]c1=O
InChIKey: DWSWFAKFOWKNCV-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin) incubated for 1 hr by ELISA analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 459.49, ALogP 2.68, HBA 7, HBD 1, PSA 109.66, QED 0.5
Compound (SMILES): O=C(c1ccc(Cl)cc1)c1coc2c1cc(O)c1ccccc12
InChIKey: DHFMPIJITCFEFT-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX-2 (unknown origin) using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA method
Measurement: IC50 = 14860 nM (pChEMBL 4.829999923706055)
Descriptors: MW 322.75, ALogP 5.18, HBA 3, HBD 1, PSA 50.44, QED 0.52