lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CC(c2ccc(Br)cc2)CC1=O
InChIKey: YMPVAJBVLOEZEX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of GST-tagged BRD4-BD1 (49 to 170 residues) (unknown origin) using Histone H4 peptide as substrate incubated for 1.5 hrs by FRET assay
Measurement: IC50 = 417000 nM (pChEMBL 3.380000114440918)
Descriptors: MW 254.13, ALogP 2.39, HBA 1, HBD 0, PSA 20.31, QED 0.75
Compound (SMILES): COc1cc(OC)cc(C(=O)N(C)c2cnc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)c(OC)c3)nc2)c1
InChIKey: OMUXPJLCHNPHQG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human N-terminal GST-tagged FGFR3 (436 to end residues) expressed in baculovirus expression system using CSKtide as substrate incubated for 30 mins in presence of ATP by off-chip mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 575.71, ALogP 3.74, HBA 10, HBD 1, PSA 95.53, QED 0.41
Compound (SMILES): O=C(Nc1ccccc1)Nc1nc(Sc2c[nH]c3ccccc23)cc(N2CCN(c3ccccn3)CC2)n1
InChIKey: XMACQIMBANOCGH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human N-terminal GST tagged VEGFR2 expressed in Sf9 insect cells using Poly- (Glu4:Tyr)-biotin substrate incubated for 45 mins by Kinase Glo Plus Luminescence kinase assay
Measurement: IC50 = 1710 nM (pChEMBL 5.769999980926514)
Descriptors: MW 522.64, ALogP 5.47, HBA 7, HBD 3, PSA 102.07, QED 0.25
Compound (SMILES): Nc1cc(S(=O)(=O)c2ccc(C(F)(F)F)cc2)cnc1C(=O)N1CCC[C@H]1CO
InChIKey: WRISKWZHYBNCLJ-LBPRGKRZSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing YFP incubated for 10 mins by halide potentiator assay
Measurement: EC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 429.42, ALogP 2.11, HBA 6, HBD 2, PSA 113.59, QED 0.77
Compound (SMILES): Cc1ccc(CN(CC(O)COc2cccc3[nH]ccc23)C(C)(C)C)cc1
InChIKey: BNRANURXPKRRKP-UHFFFAOYSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Binding affinity to beta1 adrenoceptor (unknown origin)
Measurement: Ki = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 366.51, ALogP 4.52, HBA 3, HBD 2, PSA 48.49, QED 0.65
Compound (SMILES): CC(Nc1c(Cl)cnc2cnc(-c3cnc(C(C)(C)O)nc3)cc12)c1ccccc1F
InChIKey: ICBHKKQDLXKXRF-UHFFFAOYSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Displacement of fluorescent labeled probe from human recombinant His-tagged TNFalpha (77 to 233 residues) expressed in Escherichia coli preincubated for 1 hr followed by fluorogenic probe addition and measured after 3 hrs by HTRF assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 437.91, ALogP 5.28, HBA 6, HBD 2, PSA 83.82, QED 0.44
Compound (SMILES): COc1ccc(CCCCN2CCn3c(nc4ccccc43)C2)c(F)c1
InChIKey: PRWJQIDAPSMDMT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Positive allosteric modulation of human mGlu2 receptor stably expressed in human Chem-1 cells assessed as potentiation of glutamate-induced intracellular calcium level preincubated for 30 mins followed by glutamate addition by fluorescence assay
Measurement: EC50 = 1210 nM (pChEMBL 5.920000076293945)
Descriptors: MW 353.44, ALogP 4.02, HBA 4, HBD 0, PSA 30.29, QED 0.63
Compound (SMILES): O=C(CCN1CCCc2ccccc21)Nc1ccccc1
InChIKey: OPDYSVLVMGRCCI-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from muscarinic M4 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 213.8 nM (pChEMBL 6.670000076293945)
Descriptors: MW 280.37, ALogP 3.47, HBA 2, HBD 1, PSA 32.34, QED 0.93
Compound (SMILES): CCCCCCCCC/C=C/C(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: LDPZZPXNXVORTR-GVUXWKHASA-N
Target: Medium/long-chain-fatty-acid--CoA/3-oxocholest-4-en-26-oate--CoA ligase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WQ51
Assay: Inhibition of Mycobacterium tuberculosis H37Rv FACL19 Spectra expressed in Escherichia coli BL21(DE3) cells assessed as cleavage of MEsG by spectroscopic analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 526.62, ALogP 1.1, HBA 12, HBD 4, PSA 191.78, QED 0.2
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CSCCCNC(=O)C2Cc3ccc([N+](=O)[O-])cc3CN2)[C@@H](O)[C@H]1O
InChIKey: UPRXYLMCECRARE-RRBMSBAWSA-N
Target: Phenylethanolamine N-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P11086
Assay: Competitive inhibition of C-terminal hexahistidine tag in human recombinant PNMT expressed in Escherichia coli assessed as inhibition constant using PEA as substrate in presence of 100 uM AdoMet as co-substrate by Sigma-plot analysis
Measurement: Ki = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 544.59, ALogP -0.11, HBA 13, HBD 5, PSA 203.58, QED 0.14
Compound (SMILES): CCCS(=O)(=O)Nc1cc(-c2cc(-c3ccc(N4CCNCC4)cc3)cnc2N)cc2c1OCCO2
InChIKey: BBOLTJJZURFJLA-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of recombinant human RIPK2 incubated for 2 hr by ADP-Glo assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 509.63, ALogP 3.33, HBA 8, HBD 3, PSA 118.81, QED 0.44
Compound (SMILES): CCn1cc(/C(=N/Nc2nc(-c3ccc(F)cc3)c(C#N)s2)C(F)(F)F)c2cc(-c3nc(CN4CCCCC4)cs3)ccc21
InChIKey: WWVILGUKZPRHBP-WGSLGHPRSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human C-terminal His6-tagged ATX beta expressed in Sf9 insect cells using FS-3 as substrate preincubated for 45 mins followed by substrate addition and measured at 1 min interval for 30 mins by fluorescence assay
Measurement: IC50 = 3430 nM (pChEMBL 5.460000038146973)
Descriptors: MW 637.73, ALogP 8.28, HBA 9, HBD 1, PSA 82.13, QED 0.11
Compound (SMILES): O=C1c2ccccc2C(=O)c2cc(S(=O)(=O)Nc3ccc(O)cc3)ccc21
InChIKey: CQXWZOXSWDZDPK-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Binding affinity to STAT3 (unknown origin) expressed in Escherichia coli by CM5 sensor chip immobilization based SPR assay
Measurement: Kd = 4590 nM (pChEMBL 5.340000152587891)
Descriptors: MW 379.39, ALogP 2.97, HBA 5, HBD 2, PSA 100.54, QED 0.53
Compound (SMILES): O=C(Nc1cccc(CNC(=O)c2sc3ccccc3c2OCc2ccccc2)c1)c1cccc(F)c1
InChIKey: XWOBNAGKFIZSBS-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of recombinant human SNEP1 (419 to 644 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 510.59, ALogP 6.8, HBA 4, HBD 2, PSA 67.43, QED 0.24
Compound (SMILES): COc1cc([C@@H]2CC(c3sc(-c4ccccc4)nc3C)=NN2c2ccc(S(C)(=O)=O)cc2)cc(OC)c1OC
InChIKey: CCIBBPPUXWTGSL-DEOSSOPVSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of Ovine COX-1 assessed as decrease in prostaglandin production using arachidonic acid as substrate pretreated for 15 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 = 7500 nM (pChEMBL 5.119999885559082)
Descriptors: MW 563.7, ALogP 5.9, HBA 9, HBD 0, PSA 90.32, QED 0.26
Compound (SMILES): COc1ccc(-c2nc(N/N=C(/c3c(C)[nH]c4cc(F)c(N5CCN(CCN(C)C)CC5)cc34)C(F)(F)F)sc2C#N)cc1
InChIKey: DDNPBXZHFCKIGH-AWYAZMPSSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human C-terminal His6-tagged ATX beta expressed in Sf9 insect cells using FS-3 as substrate preincubated for 45 mins followed by substrate addition and measured at 1 min interval for 30 mins by fluorescence assay
Measurement: IC50 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 628.7, ALogP 5.68, HBA 9, HBD 2, PSA 95.81, QED 0.14
Compound (SMILES): C=CC(=O)NCc1ccc(-c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2)nc1
InChIKey: MBMXKMKKFAVPBD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Inhibition of kinase tracer 236 binding to CDK13 (unknown origin) by FRET based Lantha screen Eu kinase binding assay
Measurement: IC50 = 20.9 nM (pChEMBL 7.679999828338623)
Descriptors: MW 415.5, ALogP 3.89, HBA 4, HBD 3, PSA 99.77, QED 0.49
Compound (SMILES): Cc1c(N)cccc1-c1ccnc(Nc2ccc3c(c2)N(C(C)C)[C@H](C)C(=O)N3C)n1
InChIKey: KXEMGSZLUNPCML-MRXNPFEDSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His6-tagged BRD4 bromodomain 1 (unknown origin) expressed in Escherichia coli Bl21(DE3) cells incubated for 4 hrs by FP assay
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 416.53, ALogP 4.36, HBA 6, HBD 2, PSA 87.38, QED 0.61
Compound (SMILES): CCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1CCCCC1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
InChIKey: XYPKAGBRNXNPSE-CUZNLEPHSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Displacement of [125I] [NIe75, Tyr77]Pyr-apelin-13 from YFP-tagged human APJ receptor expressed in HEK293 cell membranes incubated for 1 hr by gamma counting based Cheng-Prusoff equation analysis
Measurement: Ki = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 1216.5
Compound (SMILES): O=C(Nc1c[nH]nc1-c1cc(Cl)c(O)cc1OC(F)F)c1cnn2cccnc12
InChIKey: AYSPNZYVJHZGIG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human JAK1 (854 to 1154 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay
Measurement: Ki = 0.11 nM (pChEMBL 9.960000038146973)
Descriptors: MW 420.76, ALogP 3.33, HBA 7, HBD 3, PSA 117.43, QED 0.46
Compound (SMILES): CCC/N=C(\C)c1c(O)c2ccccc2oc1=O
InChIKey: KLTUKQUFBNNSHZ-OQLLNIDSSA-N
Target: Myosin-2 (SINGLE PROTEIN), Bos taurus
UniProt: Q9BE41
Assay: Inhibition of actin-activated bovine heart muscle myosin 2 assessed as phosphate level incubated for 6 to 24 mins by spectrophotometric method
Measurement: IC50 = 54000 nM (pChEMBL 4.269999980926514)
Descriptors: MW 245.28, ALogP 2.72, HBA 4, HBD 1, PSA 62.8, QED 0.67
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)Cn2nnc3cc(C)ccc3c2=O)cc1
InChIKey: UOFXNHJSTFHCTF-AWEZNQCLSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 336.4, ALogP 2.29, HBA 5, HBD 1, PSA 76.88, QED 0.79
Compound (SMILES): O=C(O)c1ccccc1Sc1c(O)cc(-c2ccccc2)n(-c2ccccc2)c1=O
InChIKey: SQTJYPQVUHOFMI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of N-terminal His-tagged striatal-enriched protein tyrosine phosphatase (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as inhibition of p-nitrophenyl phosphate substrate hydrolysis at pH 7 measured by plate reader method
Measurement: IC50 = 56200 nM (pChEMBL 4.25)
Descriptors: MW 415.47, ALogP 5.06, HBA 5, HBD 2, PSA 79.53, QED 0.48
Compound (SMILES): CCCn1c(=O)c2cccc(Cl)c2n2c(SC)nnc12
InChIKey: VQEXWWQSLDYNBF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of biotin-Ahx-CETFDPPLHSpTAI-NH2 binding to recombinant human full-length HA-EGFP-tagged Plk1 PBD expressed in HEK293A cells preincubated for 30 mins followed by biotin-Ahx-CETFDPPLHSpTAI-NH2 addition and measured after 1 hr by 3,3',5,5'-tetramethylbenzidine substrate based ELISA
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 308.79, ALogP 2.83, HBA 6, HBD 0, PSA 52.19, QED 0.7
Compound (SMILES): COc1ccc(C(=O)OC(C(=O)Nc2ccc(Oc3ccnc4cc(OC)c(OC)cc34)c(F)c2)C(C)(C)C)cc1
InChIKey: VTCPTOAPAILCRT-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET (unknown origin) using poly (Glu, Tyr) 4:1 as substrate measured after 30 mins by HTRF assay
Measurement: IC50 = 21.48 nM (pChEMBL 7.670000076293945)
Descriptors: MW 562.59, ALogP 6.4, HBA 8, HBD 1, PSA 105.21, QED 0.23
Compound (SMILES): CNc1ccc(-c2c3c(nn2C(C)C)CCNCC3)cc1
InChIKey: CWJKEVLEUPKOLX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-ketanserin from human 5-HT2C receptor by competitive radioligand binding assay
Measurement: Ki = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 284.41, ALogP 2.86, HBA 4, HBD 2, PSA 41.88, QED 0.91
Compound (SMILES): C=CC(=O)Nc1ccccc1Nc1ccc2c(C(=O)c3cc(OC)cc(OC)c3)cn(C)c2n1
InChIKey: CTOGOKDZTMAQHM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using poly (Glu, Tyr)4:1 as substrate incubated for 20 mins followed by [33P]-ATP addition and measured after 120 mins by radiometric hotspot assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.5, ALogP 4.69, HBA 7, HBD 2, PSA 94.48, QED 0.3
Compound (SMILES): Cc1ccccc1C(=O)/C=C1\Nc2ccccc2NC1=O
InChIKey: RUCKREZLHBQANC-GDNBJRDFSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of human JNK3 after 40 mins by [gamma-33ATP] radiometric assay relative to control
Measurement: IC50 = 3480 nM (pChEMBL 5.460000038146973)
Descriptors: MW 278.31, ALogP 3.13, HBA 3, HBD 2, PSA 58.2, QED 0.66
Compound (SMILES): Cc1ccc(-c2ccc3c(c2)N(c2ccc(Cl)cc2)C[C@@H](C)c2nnc(C)n2-3)cn1
InChIKey: APBJGATVIQPHOY-OAHLLOKOSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His/FLAG-tagged BRD4 BD1 (unknown origin) using histone H4-TetraAcetylated-biotin peptide as substrate incubated for 20 mins by AlphaLISA assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 415.93, ALogP 5.85, HBA 5, HBD 0, PSA 46.84, QED 0.41
Compound (SMILES): CC(C)Oc1ccc(Nc2cc(=O)n(CCC(=O)O)c(=O)n2Cc2ccc(Cl)cc2)cc1Cl
InChIKey: HPNBQEPLOMTGNM-UHFFFAOYSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Antagonist activity at human P2X3 receptor expressed in rat C6-BU-1 cells
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 492.36, ALogP 4.37, HBA 7, HBD 2, PSA 102.56, QED 0.46
Compound (SMILES): CCN(CC)CCNC(=O)c1c(C)[nH]c(/C=C2\C(=O)Nc3ccc(C(=O)N[C@@H](C)c4ccccc4)cc32)c1C
InChIKey: DHSBNOHGAXYJSI-FVBVXOILSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P34947
Assay: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 527.67, ALogP 4.69, HBA 4, HBD 4, PSA 106.33, QED 0.29
Compound (SMILES): COC(=O)c1ccc(CN2CCC(O)(Cn3cnc4c(cnn4-c4ccc(F)cc4)c3=O)CC2)cc1
InChIKey: LDXNAHHICJUWMO-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of recombinant human N-terminal His6-tagged full length USP7 expressed in baculovirus infected Sf21 cells using monoubiquitinated ubiquitin-rhodamine as substrate incubated for 30 mins followed by Ub-Rho addition and measured after 2 hrs by spectrophotometry
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 491.52, ALogP 2.54, HBA 9, HBD 1, PSA 102.48, QED 0.41
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1cc(C)cc(C)c1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: BCTRZSNQRZQFMR-UHFFFAOYSA-M
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of recombinant human Prolyl oligopeptidase expressed in Escherichia coli expression system using (Z)-Gly-Pro-p-nitroanilide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured for 30 mins by spectrophotometric analysis
Measurement: IC50 = 58700 nM (pChEMBL 4.230000019073486)
Descriptors: MW 440.52, ALogP 5.28, HBA 4, HBD 0, PSA 40.8, QED 0.4
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NC12CCC(C(=O)O)(CC1)CC2
InChIKey: QZWSDSOAZQAJDD-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 15 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 493.4, ALogP 5.88, HBA 3, HBD 2, PSA 79.29, QED 0.48
Compound (SMILES): Nc1nc(Cl)nc2c1ncn2Cc1cccc(C2CCOCC2)n1
InChIKey: RSXROEYEGKRILN-UHFFFAOYSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Inhibition of PDE8A1 (480 to 820 residues) (unknown origin) expressed in Escherichia coli BL21 using [3H]-cAMP substrate incubated for 15 mins by liquid scintillation counting method
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 344.81, ALogP 2.4, HBA 7, HBD 1, PSA 91.74, QED 0.73
Compound (SMILES): CC1(CN)CCN(c2cnc(Sc3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: HFZSVNQUAOVFHI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of 6x-histidine tagged human SHP2 (Met1-L525 residues) expressed in Escherichia coli BL21 Star (DE3) using IRS1_pY1172(dPEG8)pY122 incubated for 30 mins by fluorescence based DIFMUP assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 398.36, ALogP 4.08, HBA 6, HBD 2, PSA 81.06, QED 0.81
Compound (SMILES): COc1ccccc1S(=O)(=O)NCC[C@H](N)COc1ccc(C#N)c(F)c1
InChIKey: IUTBOZMIIVZGGP-AWEZNQCLSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Antagonist activity at human TRPV4 expressed in BHK or HEK MSR2 cells assessed as inhibition of TRPV4 agonist GSK634775 (EC80)-induced response incubated for 10 mins
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 393.44, ALogP 1.78, HBA 6, HBD 2, PSA 114.44, QED 0.67
Compound (SMILES): O=C(O)CN1CC(=O)Oc2c(/C=C/c3ccc([N+](=O)[O-])cc3)cccc21
InChIKey: ZDDVYHMNNOWAAZ-QPJJXVBHSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of rat lens ALR2 using D,L-glyceraldehyde as substrate preincubated for 5 mins at 30 degC followed by substrate addition and measured after 4 mins in presence of NADPH
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 354.32, ALogP 2.58, HBA 6, HBD 1, PSA 109.98, QED 0.29
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1C#Cc1nn([C@H]2CC[C@H](O)CC2)c2ncnc(N)c12
InChIKey: HRDCQGAYWSHBCI-HZCBDIJESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at -80 mV holding potential by automated Qpatch electrophysiological assay
Measurement: IC50 = 26420 nM (pChEMBL 4.579999923706055)
Descriptors: MW 534.54, ALogP 4.86, HBA 7, HBD 3, PSA 118.95, QED 0.32
Compound (SMILES): COc1ccc2cc(C(=O)NCCc3cc[n+](Cc4ccccc4C)cc3)ccc2c1.[Br-]
InChIKey: DVNUJOCOPSJJFR-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using S-butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured every minute for 10 mins by DTNB-reagent based Ellman's method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 411.53, ALogP 4.47, HBA 2, HBD 1, PSA 42.21, QED 0.46
Compound (SMILES): COc1ccc2[nH]c3c(c2c1)CCNC31CCN(Cc2cc(F)c(F)c(F)c2)CC1
InChIKey: QKYBZLLLVQZYFV-UHFFFAOYSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Potentiation of CFTR N1303K mutant (unknown origin) expressed in rat FRT cells assessed as increase in VX-770-stimulated chloride current in presence of forskolin by short circuit method
Measurement: EC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 415.46, ALogP 4.23, HBA 3, HBD 2, PSA 40.29, QED 0.63
Compound (SMILES): Cc1ccsc1C(=CCCN(C)[C@H]1CCc2onc(O)c2C1)c1sccc1C
InChIKey: ZFGNKGXSCJMQFX-INIZCTEOSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GTA 1 receptor
Measurement: IC50 = 7079.46 nM (pChEMBL 5.150000095367432)
Descriptors: MW 414.6, ALogP 5.43, HBA 6, HBD 1, PSA 49.5, QED 0.58
Compound (SMILES): O=c1[nH]ccc2nc(-c3ccccc3)cn12
InChIKey: TZYYQMDXTHSYMO-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Binding affinity to full length biotinylated 6His/Avi-tagged/Tev-fused human MEK1 expressed in Escherichia coli in presence of AMP-PNP by SPR assay
Measurement: Kd = 70000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 211.22, ALogP 1.69, HBA 3, HBD 1, PSA 50.16, QED 0.67
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cccnn2c1=O)c1ccc(Cl)c(F)c1
InChIKey: MCQKPQHLCYEXPZ-VIFPVBQESA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 349.75, ALogP 1.56, HBA 6, HBD 1, PSA 81.29, QED 0.77
Compound (SMILES): O=C(Nc1ccc2nc(N3CCOCC3)oc2c1)c1cccc(-c2ccncc2)n1
InChIKey: PAUKYBZPOFBYCW-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full length N-terminal His6-tagged human IRAK4 expressed in baculovirus infected sf9 cells using biotinylated histone H3 as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 1488 nM (pChEMBL 5.829999923706055)
Descriptors: MW 401.43, ALogP 3.37, HBA 7, HBD 1, PSA 93.38, QED 0.56
Compound (SMILES): Cn1ncc2ccc(-c3ccc4c(-c5nc(N[C@H]6CCCNC6)ncc5C(F)(F)F)c[nH]c4c3)cc21
InChIKey: JHMADRGGYHZRPX-SFHVURJKSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 491.52, ALogP 5.36, HBA 6, HBD 3, PSA 83.45, QED 0.32
Compound (SMILES): O=C1Nc2ccc([N+](=O)[O-])cc2/C1=C1/Nc2ccc(O)cc2/C1=N\OCCBr
InChIKey: ACUGFMJRKZPUIE-HPBPSMLHSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant His-tagged human FLT3 expressed in baculovirus expression system using peptide substrate incubated for 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 324 nM (pChEMBL 6.489999771118164)
Descriptors: MW 445.23, ALogP 3.2, HBA 7, HBD 3, PSA 126.09, QED 0.17
Compound (SMILES): Cc1cc(-c2ccc3[nH]nc(C(=O)Nc4ccc(OC5CCN(C)CC5)cc4)c3c2)sn1
InChIKey: IYVIYYUPMDMHRV-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: GSK3β: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 M to 0.0003 M) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 447.56, ALogP 4.72, HBA 6, HBD 2, PSA 83.14, QED 0.46
Compound (SMILES): Cl.O=C1Nc2ccccc2/C1=C1/Nc2ccccc2/C1=N\OCCN1CCCCC1
InChIKey: OJDRMVDBAOYHQY-GMNPBYEVSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant His-tagged human FLT3 expressed in baculovirus expression system using peptide substrate incubated for 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 388.47, ALogP 3.68, HBA 5, HBD 2, PSA 65.96, QED 0.48
Compound (SMILES): CC(C)N(CCSC(c1ccc(F)cc1)c1ccc(F)cc1)C1CCN(C(=O)c2ccccc2F)CC1
InChIKey: KXBNLBOZXUOIKE-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN35428 from DAT in Sprague-Dawley rat striatal membranes incubated for 120 mins by microbeta scintillation counting method
Measurement: Ki = 1530 nM (pChEMBL 5.820000171661377)
Descriptors: MW 526.67, ALogP 6.94, HBA 3, HBD 0, PSA 23.55, QED 0.3
Compound (SMILES): CON(C)C(=O)Oc1ccc(-c2cc(=O)c3c(O)cc(OC(=O)N(C)OC)cc3o2)cc1
InChIKey: MAYVYUJUNJKXFY-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of rat cortex AChE using acetylthiocholine iodide as substrate measured after 15 mins by Ellman's method
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 444.4, ALogP 3.15, HBA 9, HBD 1, PSA 127.98, QED 0.59
Compound (SMILES): Cc1nc2nonc2c(N)c1CN1CCC(OC(F)(F)F)CC1
InChIKey: WGCQGXYLXMBLPP-UHFFFAOYSA-N
Target: Membrane-bound ghrelin O-acyltransferase MBOAT4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96T53
Assay: Inhibition of human GOAT expressed in HEK293 cells harboring -preproghrelin in presence of Octanoate-BSA incubated for 5 hr by ELISA
Measurement: IC50 = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 331.3, ALogP 2.01, HBA 7, HBD 1, PSA 90.3, QED 0.92
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)CNCCNc3c4c(nc5ccccc35)CCCC4)c2)nc1OCC1CC1
InChIKey: MYLYCZDLVLCRLU-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of DYRK1alpha (unknown origin)
Measurement: IC50 = 28.3 nM (pChEMBL 7.550000190734863)
Descriptors: MW 585.73, ALogP 4.42, HBA 9, HBD 4, PSA 130.16, QED 0.18
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(C(=O)NCCNC(=O)CCc4cn(CCCCC5CCN(CC(=O)N6c7ccccc7NC(=O)c7ccccc76)CC5)cn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: OTWPYWJMLIDHOJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M1 expressed in CHO-K9 cell membranes measured after 3 hrs by radioligand competition binding assay
Measurement: Ki = 6.166 nM (pChEMBL 8.210000038146973)
Descriptors: MW 984.17, ALogP 6.15, HBA 11, HBD 3, PSA 188.19, QED 0.05
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccc(NC(=O)CCCCCCCCC(=O)NO)cc3C2)c(O)cc1O
InChIKey: HBNSYDADLFRPNT-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Inhibition of HSP90a (unknown origin)
Measurement: IC50 = 46.8 nM (pChEMBL 7.329999923706055)
Descriptors: MW 511.62, ALogP 4.94, HBA 6, HBD 5, PSA 139.2, QED 0.16
Compound (SMILES): O=c1[nH]cc(-c2cc([C@H]3C[C@@H]3C(F)F)cnn2)c(=O)[nH]1
InChIKey: NAVHOBCZULINJZ-RQJHMYQMSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of human C-terminal 6His-tagged CD73 (1 to 547 residues) expressed in HEK293F cells using 2 uM AMP as substrate by rapidfire mass spectrometry assay
Measurement: IC50 < 62 nM (pChEMBL 7.208000183105469)
Descriptors: MW 280.23, ALogP 0.89, HBA 4, HBD 2, PSA 91.5, QED 0.87
Compound (SMILES): COc1cc(NCc2cccc(-c3ccccc3)c2C)c(C)cc1CN[C@H](CO)C(=O)O
InChIKey: VIWRRHHPYXVELA-XMMPIXPASA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD1-Tag2/PD-L1-Tag1 (unknown origin) protein-protein interaction preincubated for 15 mins followed by addition of anti-Tag1-Eu3+ and anti-Tag2-XL665 measured after 2.5 hrs by HTRF assay
Measurement: IC50 = 253 nM (pChEMBL 6.599999904632568)
Descriptors: MW 434.54, ALogP 4.13, HBA 5, HBD 4, PSA 90.82, QED 0.38
Compound (SMILES): COc1cccc2cc[n+](-c3ccccc3)cc12.[Br-]
InChIKey: XKZUICNZQZUENE-UHFFFAOYSA-M
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) preincubated for 30 mins followed by substrate addition acetylthiocholineiodide measured after 40 mins by Ellman's method
Measurement: IC50 = 1420 nM (pChEMBL 5.849999904632568)
Descriptors: MW 236.29, ALogP 3.13, HBA 1, HBD 0, PSA 13.11, QED 0.62
Compound (SMILES): CCCCCn1cc(-c2ccc(F)cc2)nc1N.Cl
InChIKey: DZQWBBYVKKZPGW-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at human TLR8 stably expressed in HEK293 cells cotransfected with secreted alkaline phosphatase assessed as induction of NFkappaB activation by quanti-blue SEAP reporter gene-based spectrophotometric method
Measurement: EC50 = 1960 nM (pChEMBL 5.710000038146973)
Descriptors: MW 247.32, ALogP 3.46, HBA 3, HBD 1, PSA 43.84, QED 0.82
Compound (SMILES): COc1cc2c(cc1OCc1ccccc1)CCC(C)(CC(=O)NCCCCCCNc1c3c(nc4cc(Cl)ccc14)CCCC3)O2
InChIKey: SRUORENXKCKPFF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE expressed in HEK293 cells using acetylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 656.27, ALogP 8.62, HBA 6, HBD 2, PSA 81.71, QED 0.13
Compound (SMILES): CCc1cc2c([C@@H]3C[C@H]3CN)c(OC)ccc2o1.Cl
InChIKey: NLGAYZOAGDGYEH-QLSWKGBWSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5-HT2C receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 102.33 nM (pChEMBL 6.989999771118164)
Descriptors: MW 245.32, ALogP 3.07, HBA 3, HBD 1, PSA 48.39, QED 0.9
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2n[nH]c3ncc(-c4ccccc4OC)cc23)c1F
InChIKey: UUBVBHAUPOOCKS-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P45985
Assay: Inhibition of MEKK2- induced activation of MKK4/(unknown origin) using JNK1 as substrate in presence of [gamma-33P]-ATP by scintillation counter assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 486.5, ALogP 4.29, HBA 6, HBD 2, PSA 114.04, QED 0.36
Compound (SMILES): Cl.O=C1Nc2ccccc2/C1=C1/Nc2ccccc2/C1=N\OCCNC1CCNCC1
InChIKey: LWTGYHZPTSMGIU-RNYQJTIOSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant His-tagged human FLT3 expressed in baculovirus expression system using peptide substrate incubated for 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 20.9 nM (pChEMBL 7.679999828338623)
Descriptors: MW 403.49, ALogP 2.54, HBA 6, HBD 4, PSA 86.78, QED 0.35
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CO)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@H]1CSCC(=O)NCCCCNC(=O)CSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: KKHBTXFKUIFQOL-YLLHCLKSSA-N
Target: Prolactin-releasing peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P49683
Assay: Activation of human GPR10 overexpressed in CHO-K1 cells assessed as increase in beta arrestin recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 3784.3
Compound (SMILES): COc1ccc2c(CC(=O)N[C@@H](Cc3ccccc3)[C@H](O)CN(CC(C)C)S(=O)(=O)c3ccc(N)cc3)cc(=O)oc2c1
InChIKey: ASQKNPGXHLGLML-URLMMPGGSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of recombinant HIV1 protease measured assessed as hydrolysis of fluorogenic substrate by FRET assay
Measurement: IC50 = 16.9 nM (pChEMBL 7.769999980926514)
Descriptors: MW 607.73, ALogP 3.36, HBA 8, HBD 3, PSA 152.17, QED 0.15
Compound (SMILES): CCCC[C@@](C)(Nc1nc(N)nc2cc(F)cnc12)C(=O)O
InChIKey: FLUQUUMSIVSTAF-CQSZACIVSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 in human cryopreserved PBMC assessed as inhibition of IL-12p40 production measured after 24 hrs
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 307.33, ALogP 2.19, HBA 6, HBD 3, PSA 114.02, QED 0.75
Compound (SMILES): COc1ccccc1CNC(=O)/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC[C@]1(C)CCc2c(C)c(O)cc(C)c2O1
InChIKey: JSYLOJILKXIRSL-SPAJWBDZSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5-LO expressed in Escherichia coli BL21(DE3) assessed as reduction in LTB4 and 5-H(P)ETE formation using arachidonic acid as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured after 10 mins by RP-HPLC method
Measurement: IC50 = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 559.79, ALogP 8.6, HBA 4, HBD 2, PSA 67.79, QED 0.19
Compound (SMILES): O=C1c2ccccc2OC(c2ccccc2)C1(Br)[N+](=O)[O-]
InChIKey: MBTNAHULNUQDLP-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBC3
Assay: Inhibition of human DNMT3B expressed in Escherichia coli Rosetta-gamiTM 2(DE3) pLysS competent cells using biotinylated 6-FAM double strand DNA comprising unique CpG site [3H]-SAM incubated for 1 hrs by fluorescence based assay
Measurement: EC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 348.15, ALogP 3.37, HBA 4, HBD 0, PSA 69.44, QED 0.36
Compound (SMILES): CC1(C)OC(=O)c2ccc(Nc3ncc(-c4nc(-c5ccncc5)no4)c(N[C@H](CO)c4ccccc4)n3)cc21
InChIKey: AIFRAZQXNNPZBV-HSZRJFAPSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of recombinant human N-terminal GST-tagged HPK1 (1 to 346 residues) expressed in baculovirus infected Sf9 cells using NH2-fluorescein-RFARKGSLRQKNV-COOH as substrate incubated for 3 hrs in presence of ATP by by capillary electrophoresis method
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 535.56, ALogP 4.88, HBA 11, HBD 3, PSA 148.18, QED 0.23
Compound (SMILES): CN(C)C/C=C/C(=O)N1CCC[C@H]1C(=O)NCCc1cc2c(-c3cnn4ncccc34)ccnc2[nH]1
InChIKey: BHDLEDZNDSWKRP-GPVJQRHHSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12/cyclinK (unknown origin) using RBER-IRStide as substrate and in presence of ATP preincubated for 30 mins followed by addition of substrate measured after 1 hr by ADP-Glo reagent assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 486.58, ALogP 2.04, HBA 7, HBD 2, PSA 111.52, QED 0.37
Compound (SMILES): CN1CCCC1CCNC(=O)CCC(=O)c1ccc(F)cc1F
InChIKey: BAJUBRRHSUDSLS-UHFFFAOYSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition
Measurement: IC50 = 2720 nM (pChEMBL 5.570000171661377)
Descriptors: MW 324.37, ALogP 2.53, HBA 3, HBD 1, PSA 49.41, QED 0.78
Compound (SMILES): O=S(=O)(N1CCC(Nc2cnnc3ccc(C(c4ccc(Cl)cc4)c4nccs4)cc23)CC1)C(F)(F)F
InChIKey: QHTIIIGCFXVRNT-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Inverse agonist activity at human CB1 receptor expressed in HEK293 cells assessed as forskolin-stimulated cAMP accumulation measured after 30 mins by HTRF assay
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 568.05, ALogP 5.65, HBA 7, HBD 1, PSA 88.08, QED 0.32
Compound (SMILES): Nc1ccc(Nc2ncc(C(F)(F)F)c(NC3CC3)n2)cc1
InChIKey: XWPNWIGEIJKOEC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 309.3, ALogP 3.4, HBA 5, HBD 3, PSA 75.86, QED 0.75
Compound (SMILES): COc1cc(C(=O)NC2CCNCC2)c(F)cc1Nc1ncc2scc(-c3ccccc3OC)c2n1
InChIKey: RRSINXKFGITOLR-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of N-terminal GST-fused human truncated FAK (376 to 1052 residues) expressed in baculovirus expression system using tyrosine kinase peptide as substrate measured after 50 mins in presence of ATP by homogenous time resolved flourescence assay
Measurement: IC50 = 38.2 nM (pChEMBL 7.420000076293945)
Descriptors: MW 507.59, ALogP 4.74, HBA 8, HBD 3, PSA 97.4, QED 0.33
Compound (SMILES): CCOC(=O)N1CCC(NC(=O)Nc2ccc(OC(F)(F)F)c(F)c2)CC1
InChIKey: BABUSVPCCWYOPF-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki < 0.05 nM (pChEMBL 10.300999641418457)
Descriptors: MW 393.34, ALogP 3.47, HBA 4, HBD 2, PSA 79.9, QED 0.77
Compound (SMILES): CC(C(=O)Nc1cc(C2CC2)[nH]n1)c1cccc(C2CCN(C(=O)/C=C/CN(C)C)CC2)c1
InChIKey: JDYQFGCWGWMKSX-VMPITWQZSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Biochemical Assay: The ability of compounds to inhibit CDK7 kinase activity was tested in a TR-FRET assay using 5 nM of CDK7/CycH/MNAT1 obtained from Invitrogen, USA. Test compounds were pre-incubated with the kinase at room temperature for 60 min. After the incubation, substrate mix [100 nM Ultra-light MBP (Perkin Elmer, USA) and 1 mM ATP (Sigma)] was added. The above reaction was stopped by the addition of 40 mM EDTA after 60 minutes of kinase reaction. 1 nM Eu-labelled antiphospho-MBP antibody [Perkin Elmer, USA] was added, mixed well and the fluorescence emission at 615 nm and 665 nm [excitation at 340 nm] was measured. The final DMSO concentration in the assay was 1%. For IC50 determination, appropriate concentrations were made by ⅓rd serial dilutions of 10 mM DMSO stock solution of test compound. All the fluorescence measurements were made in a Victor 3 Multilabel Counter [Perkin Elmer, USA]. The IC50 was determined by fitting the dose response data to sigmoidal curve fitting equation using GraphPad Prism software V5. To identify compounds that inhibit CDK7 irreversibly, time depended inhibition studies were carried by pre-incubating compound with the enzyme at three time points (20, 60 and 180 min) and carrying out assay as described above.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 449.6, ALogP 3.85, HBA 4, HBD 2, PSA 81.33, QED 0.6
Compound (SMILES): CC(C)/C(=C1\NC(=O)OC1=O)c1ccc(-c2ccc3cccc(F)c3c2)[nH]c1=O
InChIKey: DZLQQWDVOFNXMT-VHEBQXMUSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Displacement of [3H]-PGE2 from human EP3 expressed in Chem-1 cell membranes incubated for 2 hrs by TopCount scintillation plate reader analysis
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 392.39, ALogP 3.97, HBA 4, HBD 2, PSA 88.26, QED 0.4
Compound (SMILES): Cn1cc(-c2cc3c(Nc4ccc(CC(=O)Nc5cc(C(C)(C)C)on5)cc4)ncnc3s2)cn1
InChIKey: OALPHMPHFSEBGR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of recombinant human GST-tagged RET cytoplasmic domain (658 to 1114 residues) expressed in baculovirus expression system using 5-FAM-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 60 mins followed by substrate addition by microfluidic assay
Measurement: IC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 487.59, ALogP 5.3, HBA 9, HBD 2, PSA 110.76, QED 0.33
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ncc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)F
InChIKey: HHXTYKXNOKWJQP-FATZIPQQSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluorescent labelled fluormone ES2 from human recombinant GST tagged ER alpha LBD ( 282 to 595 residues) expressed in baculovirus infected insect cells incubate for 20 mins measured after 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 494.51, ALogP 4.45, HBA 5, HBD 2, PSA 60.08, QED 0.48
Compound (SMILES): CC1(C)CCC[C@](C)([C@H]2CC[C@]3(C)[C@@H]2[C@H](O)C[C@@H]2[C@@]4(C)CC/C(=N\Nc5ccc(Cl)cc5)C(C)(C)[C@@H]4CC[C@]23C)O1
InChIKey: QOGMTNXIZDSBOM-AUYNSLCPSA-N
Target: Hypoxia-inducible factor 1-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q16665
Assay: Inhibition of hypoxia-induced HIF1alpha transcriptional activity in human Hep3B cells co-transfected with luciferase reporter plasmid containing six copies of HREs and pRL-CMV vector assessed as reduction in luciferase activity incubated for 24 hrs under hypoxic condition by HRE-dependent dual luciferase reporter gene assay
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 583.3, ALogP 9.5, HBA 4, HBD 2, PSA 53.85, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2c(F)c(F)c(F)c(F)c2F)cc1
InChIKey: ZSYKTLDQSMAEFY-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 744.7 nM (pChEMBL 6.130000114440918)
Descriptors: MW 488.42, ALogP 1.59, HBA 5, HBD 4, PSA 147.46, QED 0.27
Compound (SMILES): CC(C)c1cc(C(=O)c2c(Cl)cc(NCc3noc(=O)[nH]3)cc2Cl)nn(C)c1=O
InChIKey: PBCWKZGRIOGQJK-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay for Thyroid Hormone Receptor Agonist Screening: LanthaScreen TR-FRET Thyroid Receptor alpha Coactivator Assay kit (ThermoFisher) and LanthaScreen TR-FRET Thyroid Receptor beta Coactivator Assay kit (ThermoFisher) were used for agonist compound screening. Compounds in DMSO were diluted using ECHO Liquid Handler (Labcyte Inc.) into 384 plates in 10-point 3-fold series in duplicate (5 micro M final top concentration). Buffer C (ThermoFisher) was added to each well before the 4× mixture of fluorescein-SCR2-2 coactivator (200 nM final concentration), Terbium-labeled anti-GST antibody (2 nM final concentration), and TR alpha-LBD (0.4 nM final concentration) or TR beta-LBD (1.0 nM final concentration) was added. After 2 hour incubation at room temperature in dark, the TR-FRET signal was measured on an EnVision plate reader (PerkinElmer) with excitation at 340 nm and dual emission readout at 495 and 520 nm with the delay time of 100 micro second and the integration time of 200 micro second. The ratio of emission signal at 520 and at 495 was used to calculate EC50 using GraphPad Prism (GraphPad Software). In every batch of compound screening, T3 (L-3,3′,5-Triiodothyronine sodium salt, >95%) (Calbiochem) was used as reference compound. The EC50 of T3 measured were within 3-fold of the reference value provided by the assay kit manufacturer (ThermoFisher Scientific). The Z′ factors measured in every batch of screening using T3 as high percent effect (HPE) control and 0.5% DMSO as zero percent effect (ZPE) control were in the range of 0.5 to 0.8. Compounds' THR-beta selectivity values are derived from T3-selectivity normalized data.
Measurement: EC50 = 271 nM (pChEMBL 6.570000171661377)
Descriptors: MW 438.27, ALogP 2.73, HBA 8, HBD 2, PSA 122.88, QED 0.57