lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1ccc(F)cn1)c1cc(Oc2cnc(F)c(F)c2)cn2ncnc12
InChIKey: RRJSTOLWZPFHFR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate pretreated for 15 mins followed by NADPH addition measured after 8 mins by LC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 386.29, ALogP 2.98, HBA 7, HBD 1, PSA 94.3, QED 0.54
Compound (SMILES): O=c1c(-c2ccsc2)c[nH]c2c(-c3ccccn3)cnn12
InChIKey: AMPDVLJTHKQJOP-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19969
Assay: Displacement of [3H]RO15-1788 from recombinant rat GABAalpha5 receptor expressed in HEK293 cells after 1 hr
Measurement: Ki = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 294.34, ALogP 2.81, HBA 5, HBD 1, PSA 63.05, QED 0.62
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)/C=C/c2cccc(C(F)(F)F)c2)cc1
InChIKey: HMUQTPOZAOWEQH-RUDMXATFSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase-9 preincubated for 10 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 370.35, ALogP 3, HBA 3, HBD 2, PSA 89.26, QED 0.81
Compound (SMILES): c1ccc(CCN2CCN(CCCCn3nnnc3C(c3ccccc3)c3ccccc3)CC2)cc1
InChIKey: ZEIBSGCMGHPJJP-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of [3H]-5-dopamine reuptake in human DAT expressed in HEK293 cells by microbeta liquid scintillation counting method
Measurement: IC50 = 608 nM (pChEMBL 6.21999979019165)
Descriptors: MW 480.66, ALogP 4.49, HBA 6, HBD 0, PSA 50.08, QED 0.3
Compound (SMILES): Cc1cccc(C(=O)N[C@H]2C[C@@H](n3cnc4c(NCc5cccc(Br)c5)ncnc43)C2)n1
InChIKey: QYLYUTQSYHCBOD-HDICACEKSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of human CDK1/CyclinB
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 492.38, ALogP 4.04, HBA 7, HBD 2, PSA 97.62, QED 0.42
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CN1CCNCC1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N(C)[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O
InChIKey: FAKBMFDMEOVEBF-QRKBBRQHSA-N
Target: Neuromedin-U receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: O55040
Assay: Agonist activity at mouse NMUR1 expressed in CHO cells assessed as induction of Ca2+ flux measured for 180 secs by Fluo 4-AM dye-based FLIPR assay
Measurement: EC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 1275.53
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@H](N(C)C(=O)/C=C/c4ccoc4)CC[C@@]4(O)[C@@H](C2)N(S(=O)(=O)c2ccccc2C(F)(F)F)CC[C@]314
InChIKey: HOPWDLRMFCRVSM-BOWFPTEESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Measurement of Antagonistic Activity Against Orexin Receptors: The Chinese hamster ovary (CHO) cell lines CHOOX1R and CHOOX2R were established by modifying CHO cells to constantly express the NFAT-luciferase gene and either the human OX1R or human OX2R gene. Those cells were plated at 10,000 cells/well in 96-well multiplates with DMEM (manufactured by Sigma-Aldrich Co. LLC) supplemented with 5% FBS (manufactured by Thermo Scientific Inc.) and incubated at 37° C. and 5% CO2 for 48 hours. After removal of the medium, 100 μL of an assay buffer (20 mM HEPES (manufactured by Sigma-Aldrich Co. LLC), Hank's balanced salt solution (manufactured by Gibco), 0.1% BSA (manufactured by Sigma-Aldrich Co. LLC), 2.5 mM probenecid acid (manufactured by Wako Pure Chemical Industries, Ltd.), pH 7.4) containing 5 μM Fura-2AM (manufactured by Cayman Chemical Co.) was added to each well, and incubated at 37° C. and 5% CO2 for 60 minutes. After removal of the buffer containing Fura-2AM, 75 μL of the assay buffer was added to each well. Then, 25 L of the assay buffer containing a test compound at various concentrations and OX-A (manufactured by Peptide Institute, Inc.) was added to start the reaction. The change in intracellular calcium ion concentration induced by the reaction was evaluated by the ratio of fluorescent intensities, which were measured at a wavelength of 510 nm based on the two wavelength excitation approach using FDSS 7000 (manufactured by Hamamatsu Photonics K.K.) with fluorescence excitation at 340 nm and 380 nm. A concentration-response curve on the antagonistic activity was plotted from the values of maximal fluorescent intensity ratio determined when various concentrations of a test compound were added in the presence of 300 μM of OX-A, where a value of maximal fluorescent intensity ratio determined by adding 300 pM of OX-A alone corresponds to 100% and a value of maximal fluorescent intensity ratio determined by adding the assay buffer alone corresponds to 0%. Based on the resulting non-linear regression curve, the 50% maximal inhibitory concentration (IC50) was calculated. Each test compound was dissolved in DMSO to a concentration of 10 mM (the final concentration of DMSO was 1%), and then diluted with the assay buffer to give a final concentration of 3.0×10−10 M to 1.0×10−5 M (a common ratio of 3), while OX-A was diluted to a final concentration of 300 pM. The experiment was performed in quadruplicate plates, and the results of the four independent measurements were averaged to give the value of each reaction, and then the IC50 of a sample was calculated. If the sample number was 2 or more, the averaged IC50 was used.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 644.67, ALogP 4.39, HBA 7, HBD 1, PSA 109.52, QED 0.4
Compound (SMILES): COc1ccccc1N1CCN(CCCNC(=O)Oc2cccc(-c3cccc(C(N)=O)c3)c2)CC1
InChIKey: HQDIIIDLDYDDHJ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human dopamine D2 receptor-short expressed in CHO-K1 cells assessed as reduction in adenylyl cyclase activator NKH 477 induced cAMP accumulation preincubated for 10 mins followed by NKH 477 addition by HTRF assay
Measurement: EC50 = 54.2 nM (pChEMBL 7.269999980926514)
Descriptors: MW 488.59, ALogP 3.76, HBA 6, HBD 2, PSA 97.13, QED 0.45
Compound (SMILES): COc1ccc(-c2cc(Nc3ncnc4cc(OC)c(OC)cc34)n[nH]2)cc1
InChIKey: ZHRZUJDEOZWDOA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of recombinant human CDK5/p25 expressed in Escherichia coli using histone H1 as substrate after 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 377.4, ALogP 3.79, HBA 7, HBD 2, PSA 94.18, QED 0.53
Compound (SMILES): Cc1cn2cc(NC(=O)c3ccc(N4CCN(C)CC4)cc3)nc2c(C)n1
InChIKey: TVJPLGCKQZRBMI-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 364.45, ALogP 2.35, HBA 6, HBD 1, PSA 65.77, QED 0.77
Compound (SMILES): CCc1cccc(NC(=O)Nc2ccc(-c3ccnc4[nH]nc(C(F)(F)F)c34)cc2)c1
InChIKey: KEHOCJQBAQEQIW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 425.41, ALogP 5.85, HBA 3, HBD 3, PSA 82.7, QED 0.38
Compound (SMILES): Nc1nc(-c2ccc(O)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: MDIQQNWAXLRRDO-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 319.32, ALogP 1.83, HBA 7, HBD 2, PSA 98.44, QED 0.59
Compound (SMILES): O=C(NCCc1cn[nH]c1)c1cc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)ccc1F
InChIKey: XLDRYKLVYHCCSJ-ICSRJNTNSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Bos taurus
UniProt: P43249
Assay: Inhibition of bovine GRK5 after 5 mins after 5 mins in presence of ATP by phosphorimaging assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 466.51, ALogP 3.02, HBA 6, HBD 3, PSA 97.5, QED 0.47
Compound (SMILES): COc1cc2c(cc1OC)C(=O)/C(=C/c1ccc(CN3CCN(C)CC3)c(O)c1)O2
InChIKey: BQJUWCUFUNRLRW-JJFYIABZSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate measured after 15 mins by Ellman's method
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 410.47, ALogP 2.77, HBA 7, HBD 1, PSA 71.47, QED 0.76
Compound (SMILES): Cc1cc(Cl)cc(C)c1C(=O)c1sc2cc(O)ccc2c1Oc1ccc(/C=C/C(=O)O)cc1
InChIKey: KDWZGXWBBPBEFR-BJMVGYQFSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of [3H]estradiol from full length recombinant human ESR1 expressed in insect cells by radiometric assay
Measurement: Ki = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 478.95, ALogP 7, HBA 5, HBD 2, PSA 83.83, QED 0.23
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)CSSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C)NC1=O
InChIKey: XGGKXZLMFNTAIQ-DOBVYHFCSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of biotinylated K-Ras G12D mutant (unknown origin) assessed as reduction in SOS1 (564 to 1049 residues)-mediated BODIPY-GDP-GTP exchange after 1 hr by TR-FRET assay
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 2545.06
Compound (SMILES): CCCCCCCCCCCCCCCCCC(=O)NC[C@H]1CC[C@H](C(=O)N[C@@H](CCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)NC(CC2CCCCC2)C(=O)N[C@@H](CC(C)C)C(=O)NC(CCCC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)O)C(=O)O)CC1
InChIKey: QVEPKOTWIJQVBS-IDCDJFNKSA-N
Target: Neuromedin-U receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: O55040
Assay: Agonist activity at mouse NMUR1 expressed in CHO cells assessed as increase in intracellular calcium influx after 180 secs by Fluo 4-AM dye based FLIPR assay
Measurement: EC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 1937.49
Compound (SMILES): N/C(=N/C(=N\S(=O)(=O)c1ccc(Cl)cc1)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1)c1cccc(Br)c1
InChIKey: QUCYFNBWYXSWAL-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: P47936
Assay: Displacement of [3H]CP55940 from mouse CB2R expressed in CHOK1 cell membranes
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 655.41, ALogP 6.71, HBA 3, HBD 1, PSA 100.48, QED 0.19
Compound (SMILES): COc1ccc2c(C(=O)c3cc(OC)c(OC)c(OC)c3)cn(S(=O)(=O)c3cccc(/C=C/C(=O)NO)c3)c2c1
InChIKey: VYTJGUNWINJKES-DHZHZOJOSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using fluorogenic substrate by fluorescence assay
Measurement: IC50 = 275.35 nM (pChEMBL 6.559999942779541)
Descriptors: MW 566.59, ALogP 3.66, HBA 10, HBD 2, PSA 142.39, QED 0.13
Compound (SMILES): CNc1nc(C#Cc2ccc(Cl)s2)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(C(=O)NCCN)C[C@H]12
InChIKey: WEUXHMZSSMXXPN-RUZZFIIFSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of [3H]mazindol binding to recombinant human SERT expressed in HEK293 cell membranes preincubated for 10 mins followed by radioligand addition measured after 90 mins by micro beta scintillation counting analysis
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 487.97, ALogP 0.34, HBA 10, HBD 5, PSA 151.21, QED 0.32
Compound (SMILES): NS(=O)(=O)c1ccc(-n2c(=O)c3cc4c(=O)n(-c5ccc(S(N)(=O)=O)cc5)c(=O)c4cc3c2=O)cc1
InChIKey: GDAUHUHJDBPFIE-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 pre-incubated for 10 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 250.9 nM (pChEMBL 6.599999904632568)
Descriptors: MW 526.51, ALogP -0.81, HBA 10, HBD 2, PSA 198.46, QED 0.3
Compound (SMILES): NCc1cc(O[C@@H]2CCCN(C(=O)Nc3ccccc3)C2)nc(C(F)(F)F)c1
InChIKey: NPNATZWDBSJWKE-OAHLLOKOSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P28300
Assay: Inhibition of human LOX expressed in HEK cells assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition in presence of 0.1% BSA measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 394.4, ALogP 3.63, HBA 4, HBD 2, PSA 80.48, QED 0.83
Compound (SMILES): COc1cc([C@@H](O)P(=O)(O)CC[C@H](N)C(=O)O)cc([N+](=O)[O-])c1O
InChIKey: PEXVMHLARUAHNC-MADCSZMMSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Agonist activity at mGlu4 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay
Measurement: EC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 364.25, ALogP 0.37, HBA 8, HBD 5, PSA 193.45, QED 0.24
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCC(Cc3ccccc3)CC2)ccc1OCCCCCCN1CCc2ccccc2C1
InChIKey: JNNYJEKQVHDGIN-FBMGVBCBSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of AChE in rat cortex homogenates using acetylthiocholine chloride as substrate measured after 15 mins by Ellman's method
Measurement: IC50 = 21500 nM (pChEMBL 4.670000076293945)
Descriptors: MW 566.79, ALogP 7.19, HBA 4, HBD 0, PSA 42.01, QED 0.16
Compound (SMILES): O=S(=O)(c1ccccc1)N1C[C@H]2OC34CCC1C2C31CCN(CC2CC2)C4Cc2ccc(O)cc21
InChIKey: BKQBFRVSDQFWGQ-HRVQGIQQSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U-69,593 from human kappa opioid receptor expressed in CHO cells
Measurement: Ki = 0.658 nM (pChEMBL 9.180000305175781)
Descriptors: MW 492.64, ALogP 3.29, HBA 5, HBD 1, PSA 70.08, QED 0.71
Compound (SMILES): NCCSc1nc(-c2ccc(F)cc2)c(-c2ccnc(Nc3ccccc3)c2)[nH]1
InChIKey: MUOFVOPPHGCPBQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human N-terminal GST-fused EGFR L858R mutant (669 to 1210 residues) expressed in baculovirus using TK-substrate-biotin preincubated for 30 mins followed by substrate addition measured after 15 mins by HTFR assay
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 405.5, ALogP 5.07, HBA 5, HBD 3, PSA 79.62, QED 0.37
Compound (SMILES): Cc1nc(-c2cccc3ccccc23)sc1C(=O)N1CCC(CO)CC1
InChIKey: OZMVYBUWNRHUPA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at recombinant human 5-HT2B receptor expressed in HEK293E cells assessed as induction of intracellular Ca2+ levels after 90 secs by Fluo-4-dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.49, ALogP 4.12, HBA 4, HBD 1, PSA 53.43, QED 0.76
Compound (SMILES): COc1cc(OCc2cccc(-c3ccccc3)c2C)cc(OC)c1CNCCNC(C)=O
InChIKey: OYNIISWIMDFFAF-UHFFFAOYSA-N
Target: Programmed cell death 1 ligand 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZQ7
Assay: Binding affinity to PDL1 (unknown origin) assessed as reduction in PDL1/PD1 protein-protein interaction preincubated for 15 mins followed by PD1 addition and measured after 15 mins by HTRF binding assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 448.56, ALogP 4.48, HBA 5, HBD 2, PSA 68.82, QED 0.42
Compound (SMILES): CCn1nnc([C@H]2O[C@@H](n3cnc4c(NCc5cccc(Br)c5)ncnc43)[C@H](O)[C@@H]2O)n1
InChIKey: QPIBSUKMBDQPIK-QCUYGVNKSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from recombinant human adenosine A3A receptor expressed in CHO cell membranes after 3 hrs by microbeta scintillation counting
Measurement: Ki = 0.393 nM (pChEMBL 9.40999984741211)
Descriptors: MW 502.33, ALogP 1.2, HBA 12, HBD 3, PSA 148.92, QED 0.35
Compound (SMILES): CCS(=O)(=O)c1ccc(Oc2ccc(F)cc2F)c(-c2cn(C)c(=O)c3cncn23)c1
InChIKey: NZEPQKGPMJEKOH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: In Vitro Enzyme Inhibition Assay: Determination of the IC50 for the heterocyclic derivative BRD4 inhibitors disclosed herein was performed as follows. His-tagged BRD4 was cloned, expressed and purified to homogeneity. Filipakopoulos et al., Nature 468:1067 (2010). BRD4 binding and inhibition was assessed by monitoring the interaction of biotinylated H4-tetraacetyl peptide (AnaSpec, H4K5/8/12/16(Ac), biotin-labeled) with the target using the AlphaScreen technology (Life Technologies). In a 384-well ProxiPlate BRD4(BD1) (2 nM final) was combined with peptide (15 nM final) in 50 mM HEPES (pH 7.3), 10 mM NaCl, 0.25 mM TCEP, 0.1% (w/v) BSA, and 0.005% (w/v) Brij-35 either in the presence of DMSO (final 0.4% DMSO) or compound dilution series in DMSO. After 20 min incubation at room temp, Alpha streptavidin donor beads and Nickel Chelate acceptor beads were added to a final concentration of 5 μg/mL. After 2 hr of equilibration, plates were read on an Envision instrument and the IC50 was calculated using a four parameter non-linear curve fit. Chemistry Example 1 (2-methyl-4-phenylisoquinolin-1-one) had an IC50 of 2.782 μM in this assay format.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 445.45, ALogP 3.56, HBA 7, HBD 0, PSA 82.67, QED 0.47
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)/C=C/c2cc(Cl)cc(Cl)c2)cc1
InChIKey: GFLQPLACZHTKTI-LZCJLJQNSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase-9 preincubated for 10 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 228.5 nM (pChEMBL 6.639999866485596)
Descriptors: MW 371.25, ALogP 3.29, HBA 3, HBD 2, PSA 89.26, QED 0.81
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(-c4ccccc4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1
InChIKey: ALJORCZKMBZYCR-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 636 nM (pChEMBL 6.199999809265137)
Descriptors: MW 570.7, ALogP 5.55, HBA 7, HBD 2, PSA 128.17, QED 0.24
Compound (SMILES): Cc1nc(NC2CCCC2)sc1-c1nc(Nc2ccc(N3CCC(N(C)C)CC3)cn2)ncc1F
InChIKey: LDHMPOHMNQEDFG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/cyclin D1 (unknown origin) in presence of [gamma-33P]-ATP by KINOMEscan assay
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 496.66, ALogP 5.07, HBA 9, HBD 2, PSA 82.1, QED 0.47
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(N)=O
InChIKey: OFHSVORZHRSITE-ZRALRULHSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1429.69
Compound (SMILES): CC(=O)Nc1cc(C(F)(F)F)c(-c2nc(N3CCOCC3)nc(N3CCOCC3)n2)cn1
InChIKey: LAGOIAGOMPRLAM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR in human A2058 cells assessed as reduction in phosphorylation of S6 at ser235/236 residues after 1 hr by in-cell Western method
Measurement: IC50 = 729 nM (pChEMBL 6.139999866485596)
Descriptors: MW 453.43, ALogP 1.58, HBA 9, HBD 1, PSA 105.6, QED 0.74
Compound (SMILES): COc1cccc(S(=O)(=O)n2c(CCCC(=O)O)cc3cc(C(F)(F)F)ccc32)c1
InChIKey: FZRGQHOQBMCEHM-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human GAL4-fused PPARgamma LBD expressed in African green monkey COS7 cells co-expressing 5Gal4 pGL3 TK Luc after overnight incubation by luciferase reporter gene assay
Measurement: EC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 441.43, ALogP 4.31, HBA 5, HBD 1, PSA 85.6, QED 0.59
Compound (SMILES): COc1cc(-c2nc3ccccc3c(=O)[nH]2)ccc1O
InChIKey: OIUTUDZPVAEFTJ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in yeast microsomal membranes using 7-ethoxyresorufin/3-cyano-7-ethoxycoumarin/7-ethoxy-methyloxy-3-cyanocoumarin as substrate by fluorescence assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 268.27, ALogP 2.3, HBA 4, HBD 2, PSA 75.21, QED 0.75
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCN1C(=O)CNCC21
InChIKey: XJMFPTCMAYQIDJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) using TK as substrate after 30 mins by HTRF assay
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 557.08, ALogP 3.84, HBA 9, HBD 3, PSA 125.55, QED 0.4
Compound (SMILES): Brc1cccc(-c2nnnn2CCCN2CCC(Cc3ccccc3)CC2)c1
InChIKey: DKZPVHDFXXVTMN-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of re-uptake of [3H]-DA at human DAT expressed in HEK293 cells by liquid scintillation counting
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.39, ALogP 4.45, HBA 5, HBD 0, PSA 46.84, QED 0.54
Compound (SMILES): CNC(C)Cc1cc(C#N)cc(OCc2ccc3c(C)cc(N)nc3c2)c1
InChIKey: PUGNZMCPLRURSU-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Mus musculus
UniProt: P29477
Assay: Inhibition of recombinant mouse macrophage iNOS expressed in Escherichia coli assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of 10 uM H4B by hemoglobin capture assay
Measurement: Ki = 10800 nM (pChEMBL 4.96999979019165)
Descriptors: MW 360.46, ALogP 3.73, HBA 5, HBD 2, PSA 83.96, QED 0.7
Compound (SMILES): O=C(NCCCc1ccc(O)cc1)c1cc2ccc(O)cc2oc1=O
InChIKey: IRTLXYIOFBGNOF-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14550
Assay: Inhibition of recombinant human AKR1A1 using pyridine-3-aldehyde as substrate
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 339.35, ALogP 2.57, HBA 5, HBD 3, PSA 99.77, QED 0.49
Compound (SMILES): COc1cc2ncnc(-n3nc(Nc4ccc(OCCN5CCCC5)c(Cl)c4)nc3N)c2cc1OC
InChIKey: LNCWXTGZLVPWLT-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin stimulated INSR phosphorylation in human HeLa cells preincubated for 1 hr followed by insulin addition measured after 5 mins by Western blot analysis
Measurement: EC50 = 4170 nM (pChEMBL 5.380000114440918)
Descriptors: MW 510.99, ALogP 3.68, HBA 11, HBD 2, PSA 125.47, QED 0.34
Compound (SMILES): C(=C/CN(C[C@H]1Cc2ccccc2CN1)[C@H]1CCCc2cccnc21)\CNCc1ccccn1
InChIKey: KKUZNBPYLQBJGJ-HGYCFVDHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 1560 nM (pChEMBL 5.809999942779541)
Descriptors: MW 453.63, ALogP 4.22, HBA 5, HBD 2, PSA 53.08, QED 0.38
Compound (SMILES): COC(=O)N[C@@H]1CC(C)(C)c2ccc(Nc3nc(NCC(F)F)c4occc4n3)cc2NC1=O
InChIKey: FIPLZUDZTBBURI-OAHLLOKOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 474.47, ALogP 3.99, HBA 8, HBD 4, PSA 130.41, QED 0.42
Compound (SMILES): C=CCn1cc(C(=O)N(C)C2CCN(c3cc(OC)nc(C)n3)CC2)c2cc[nH]c2c1=O
InChIKey: DKDFRNZFAZHONL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of recombinant human N-terminal His6-FLAG-tagged BRD4 bromodomain 1 expressed in Rosetta2 (DE3) pLysS cells after 60 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 436.52, ALogP 2.36, HBA 7, HBD 1, PSA 96.35, QED 0.6
Compound (SMILES): C=CC(=O)N1CCC(OCCn2c(=O)c(-c3c(Cl)c(OC)cc(OC)c3Cl)cc3cnc(NC)nc32)C1
InChIKey: DSFNDCSGZPQFHC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Activity Assay: A Caliper-based kinase assay (Caliper Life Sciences, Hopkinton, Mass.) was used to measure inhibition of FGFR family (FGFR1, FGFR2, FGFR3, FGFR4) kinase activity of a compound of Formula (III). Serial dilutions of test compounds were incubated with either human recombinant FGFR1 (0.5 nM), FGFR2 (0.1 nM, FGFR3 (0.9 nM), or FGFR4 (2 nM), ATP (FGFR1: 100 μM; FGFR2: 75 μM; FGFR3: 120 μM; FGFR4: 250 μM) and a phosphoacceptor peptide substrate FAM-KKKKEEIYFFF-CONH2 (1 μM) at room temperature for 3 h. The reaction was then terminated with EDTA, final concentration 20 mM and the phosphorylated reaction product was quantified on a Caliper LabChip 3000. Percent inhibition was calculated for each compound dilution and the concentration that produced 50% inhibition was calculated.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 548.43, ALogP 3.63, HBA 9, HBD 1, PSA 107.81, QED 0.4
Compound (SMILES): Cc1cccc(S(=O)(=O)NCCCN2CC=C(c3c(C)[nH]c4ccc(Cl)cc34)CC2)c1
InChIKey: VHQMQGFUKJJJQZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in CHO-K1 cell membranes after 60 mins by scintillation counting
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 458.03, ALogP 4.9, HBA 3, HBD 2, PSA 65.2, QED 0.5
Compound (SMILES): COC(=O)CCCCN1C(=O)[C@H](CC(=O)OC(C)(C)C)N=C(c2ccccc2)c2ccccc21
InChIKey: OTPFLQQXFOYVOP-NRFANRHFSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human KDAC6 using FITC-labeled histone H4 acetylated peptide as substrate after 60 mins by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 464.56, ALogP 4.31, HBA 6, HBD 0, PSA 85.27, QED 0.43
Compound (SMILES): NCCNS(=O)(=O)c1ccc(-c2ccc(CSc3nc4c(c(=O)[nH]3)CCC4)cc2)cc1
InChIKey: YDCCHZDGDMSTQT-UHFFFAOYSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of recombinant human MMP1 expressed in mouse NSO cells using fTHP-15 as substrate preincubated for 30 mins followed by substrate addition measured immediately by fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 456.59, ALogP 2.45, HBA 6, HBD 3, PSA 117.94, QED 0.35
Compound (SMILES): Cc1nnc2n1[C@H]1CCN(Cc3cc4nc(-c5cccc6[nH]ccc56)nc(N5CCOCC5)c4s3)C[C@H]1CC2
InChIKey: ZRNOFVLNBAYQHX-CLOONOSVSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins in presence of ATP by HTRF method
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 540.7, ALogP 4.59, HBA 9, HBD 1, PSA 87.99, QED 0.36
Compound (SMILES): C=CC(=O)Nc1cc(Nc2n[nH]c3cc(-c4cccc(C(F)(F)F)c4)ccc23)c(OC)cc1N(C)CCN(C)C
InChIKey: QYIXKZSSLXPWRL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type human N-terminal GST-tagged EGFR cytoplasmic domain (669 to 1210 end amino acid residues) expressed in baculovirus expression system using TK peptide substrate preincubated with enzyme for 30 mins followed by substrate addition measured after 25 mins by HTRF assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 552.6, ALogP 6.12, HBA 6, HBD 3, PSA 85.52, QED 0.21
Compound (SMILES): Nc1n[nH]c2cccc(-c3cccc(NC(=O)C4(C(=O)Nc5ccc(Cl)cc5Cl)CC4)c3)c12
InChIKey: CGYBDLADVICDCX-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
Assay: Inhibition of EphB4 (unknown origin) after 60 mins by ADP-Glo assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 480.36, ALogP 5.48, HBA 4, HBD 4, PSA 112.9, QED 0.28
Compound (SMILES): Cc1cc(COc2ccc(S(=O)(=O)N(C)[C@@H]3CCC[C@@H]3C(=O)NO)cc2)c2ccccc2n1
InChIKey: YCPPWBXGHRHAGM-JTHBVZDNSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of recombinant TACE catalytic domain (unknown origin) using Abz-LAQAVRSSSR-Dpa as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by FRET assay
Measurement: IC50 = 0.631 nM (pChEMBL 9.199999809265137)
Descriptors: MW 469.56, ALogP 3.42, HBA 6, HBD 2, PSA 108.83, QED 0.41
Compound (SMILES): O=C(Nc1cc(F)c(Cl)c(F)c1)c1cc(S(=O)(=O)N2CCOCC2)c(Cl)cc1Cl
InChIKey: FPOZIKVHNOFZAH-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of ATX (unknown origin) expressed in human A2058 cells assessed as inhibition of LPC-induced cell invasion after 20 hrs by calcein-AM dye based matrigel-mediated Boyden chamber assay
Measurement: IC50 = 740.4 nM (pChEMBL 6.130000114440918)
Descriptors: MW 485.72, ALogP 4.2, HBA 4, HBD 1, PSA 75.71, QED 0.66
Compound (SMILES): COc1ccccc1-c1ncc(N[C@@H](CO)c2ccccc2)cc1-c1ccc2[nH]nc(C)c2c1
InChIKey: ZEBYXZHDTZMGNC-SANMLTNESA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human FGFR3 using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 450.54, ALogP 5.75, HBA 5, HBD 3, PSA 83.06, QED 0.29
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](NS(=O)(=O)NCCCC#N)C1
InChIKey: STIMBIXZKCCFKW-TXEJJXNPSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 using FITC-KGGEEEEYFELVKK as substrate in presence of 1 mM ATP by mobility shift assay
Measurement: IC50 >= 8000 nM (pChEMBL 5.0970001220703125)
Descriptors: MW 363.45, ALogP 0.65, HBA 6, HBD 3, PSA 126.8, QED 0.59
Compound (SMILES): Cc1ccc2c(c1)C=Cc1cc(C)ccc1C2c1cn(Cc2ccc(C(=O)Nc3nnn[nH]3)o2)c(=O)[nH]c1=S
InChIKey: PVKNPGQAFNALOI-UHFFFAOYSA-N
Target: P2Y purinoceptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41231
Assay: Displacement of N-(2-(3-((7-Chloro-4-(1-methyl-2-oxo-4-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4H-benzo[5,6]cyclohepta[1,2-d]thiazol-2-yl)-amino)propanamido)ethyl)-6-(3-(5,5-difluoro-7,9-dimethyl-5H-4-lamba4,5-lambda4-dipyrrolo[1,2-c:2,1-f ][1,3,2]diazaborinin-3-yl)-propanamido)hexanamide from recombinant human N-terminal NLuc-tagged P2Y2R expressed in human 1321N1 cells incubated for 1 hr by furimazine-based NanoBRET assay
Measurement: Ki = 35.48 nM (pChEMBL 7.449999809265137)
Descriptors: MW 537.61, ALogP 4.59, HBA 8, HBD 3, PSA 134.49, QED 0.27
Compound (SMILES): NC(=O)C12CC3CC(C1)C(CC(=O)N1CC(O)C1)(c1ccc(F)cc1)C(C3)C2
InChIKey: NFCUMZHFYCWOFO-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 386.47, ALogP 1.97, HBA 3, HBD 2, PSA 83.63, QED 0.83
Compound (SMILES): CC(C)(C)c1cccc(Nc2ncnc3cc(NC(=O)CCCCCCC(=O)NO)sc23)c1
InChIKey: RBESUUPNLTTXDN-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length recombinant human GST fused His6-tagged HDAC6 expressed in baculovirus infected High5 cells using Boc-Lys(epsilon-acetyl)-AMC as substrate measured after 3 hrs
Measurement: IC50 = 56.02 nM (pChEMBL 7.25)
Descriptors: MW 469.61, ALogP 5.52, HBA 7, HBD 4, PSA 116.24, QED 0.18
Compound (SMILES): Nc1n[nH]c(N2CCC(N(CCc3ccc(Cl)cc3)CC3CCCCC3)CC2)n1
InChIKey: XUFFJSHQBWPHFZ-UHFFFAOYSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of human recombinant full length C-terminal His-tagged chitotriosidase expressed in CHO-K1 cells using 4-methylumbelliferyl-beta-D-N,N',N\"\"-triacetylchitotrioside as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 417, ALogP 4.13, HBA 5, HBD 2, PSA 74.07, QED 0.71
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)Sc1ccccc1Cl
InChIKey: OPKGTAFVJJSZJO-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of full length recombinant human His-tagged IDO1 expressed in mouse LLTC cells using L-tryptophan as substrate after 24 hrs
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 298.19, ALogP 5.32, HBA 2, HBD 1, PSA 29.1, QED 0.76
Compound (SMILES): Cc1nc2n(c(=O)c1CCN1CCC(c3noc4cc(F)ccc34)CC1)CCCC2(C)O
InChIKey: BQYKGUJOFYMQBC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 440.52, ALogP 3.26, HBA 7, HBD 1, PSA 84.39, QED 0.67
Compound (SMILES): COc1cc2c(cc1OC)[C@H]1CCC[N+]1(C)CC2.[I-]
InChIKey: DYXDGMZLSAHNNL-FMVIYNIGSA-M
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Displacement of [3H]epibatidine from rat alpha3beta4 nAChR expressed in HEK293 cell membranes after 4 hrs by scintillation counting method
Measurement: Ki = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 248.35, ALogP 2.54, HBA 2, HBD 0, PSA 18.46, QED 0.75
Compound (SMILES): COC(=O)NCCc1cccc2ccc(OC)nc12
InChIKey: WJPNWUVEDASJGE-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Intrinsic activity at human MT1 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 260.29, ALogP 2.14, HBA 4, HBD 1, PSA 60.45, QED 0.91
Compound (SMILES): COc1ccc2sc(C(=O)N(C)Cc3cccc(F)c3)cc2c1
InChIKey: HHUOQHKKRABAQB-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of full length recombinant GST-tagged human DYRK1B expressed in baculovirus using KKISGRLSPIMTEQ-NH2 as substrate after 15 mins
Measurement: IC50 = 206 nM (pChEMBL 6.690000057220459)
Descriptors: MW 329.4, ALogP 4.32, HBA 3, HBD 0, PSA 29.54, QED 0.71
Compound (SMILES): C=CC(=O)Nc1cccc(Cl)c1Nc1ncc(OCc2cc(OC)cc(OC)c2Cl)cn1
InChIKey: QCCLMRFWXCMZDY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of His-tagged cytoplasmic recombinant human FGFR3 (399 to 806 residues) expressed in baculovirus expression system using Tyr 4 peptide as substrate incubated for 1 hr by FRET-based Z'-Lyte assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 475.33, ALogP 5.25, HBA 7, HBD 2, PSA 94.6, QED 0.41
Compound (SMILES): NC(=O)c1cccc(C2C[C@H]3CC[C@H](C2)N3CCCCN2C(=O)c3ccccc3C2=O)c1
InChIKey: ZSAABBVZFWEOFF-NHCUHLMSSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPN from recombinant human delta opioid receptor expressed in CHOK1 cell membranes
Measurement: Ki = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 431.54, ALogP 3.57, HBA 4, HBD 1, PSA 83.71, QED 0.54
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2cccc(Cl)c2c(=O)n1-c1cc[nH]n1
InChIKey: HMWYMSWJWLPMCS-VIFPVBQESA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of human full length PI3K p110delta/p85 alpha using PIP2/ATP as substrate after 30 mins by TR-FRET assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 407.83, ALogP 2.18, HBA 9, HBD 3, PSA 151.19, QED 0.47
Compound (SMILES): CN1CCC(Nc2cccc(-c3nc4ccc(OCCCN5CCCC5)cc4o3)c2)CC1
InChIKey: LKJHXIBCNZAWKC-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonist activity at TLR9 in human PBMC assessed as inhibition of CpGA-induced IFN-alpha production after 18 hrs by ELISA
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 434.58, ALogP 4.87, HBA 6, HBD 1, PSA 53.77, QED 0.51
Compound (SMILES): c1ccc(CN(CCCCN(C[C@H]2Cc3ccccc3CN2)[C@H]2CCCc3cccnc32)Cc2ccccc2)cc1
InChIKey: PCNVYDZQYJVYOG-XDSPJLLDSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 2240 nM (pChEMBL 5.650000095367432)
Descriptors: MW 544.79, ALogP 6.96, HBA 4, HBD 1, PSA 31.4, QED 0.2
Compound (SMILES): O.O=C(Nc1cccc(C(=O)Nc2ccc(S(=O)(=O)[O-])c3cc(S(=O)(=O)[O-])cc(S(=O)(=O)[O-])c23)c1)Nc1cccc(C(=O)Nc2ccc(S(=O)(=O)[O-])c3cc(S(=O)(=O)[O-])cc(S(=O)(=O)[O-])c23)c1.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
InChIKey: FLINBQMOKZJBEC-UHFFFAOYSA-H
Target: Signal transducer and activator of transcription 1-alpha/beta (SINGLE PROTEIN), Homo sapiens
UniProt: P42224
Assay: Inhibition of 5-carboxyfluorescein-GpYDKPHVL-OH binding to STAT1 (unknown origin) pre-incubated for 1 hr before fluorescent-labelled peptide addition by fluorescence polarization assay
Measurement: IC50 = 33200 nM (pChEMBL 4.480000019073486)
Descriptors: MW 1031
Compound (SMILES): Cc1ccc(Sc2ccccc2N2CCN(CCc3c(C)nc4n(c3=O)CCCC4O)CC2)c(C)c1.Cl
InChIKey: BVHJKISMBSDSFW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 504.7, ALogP 4.51, HBA 7, HBD 1, PSA 61.6, QED 0.53
Compound (SMILES): CC(=O)NC(C)c1ccc2nc(-c3ccc(Oc4cccc(OCC5CC5)c4)cn3)oc2c1
InChIKey: IUXDAQZCLLCHAM-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of ACC1 in human HCT116 cells assessed as reduction of [14C]acetate uptake preincubated for 60 mins followed by addition of [14C]acetate and measured after 2 hrs by scintillation counting analysis
Measurement: IC50 = 9.9 nM (pChEMBL 8)
Descriptors: MW 443.5, ALogP 5.67, HBA 6, HBD 1, PSA 86.48, QED 0.38
Compound (SMILES): O=C(NCc1ccccc1)c1cccc(NCc2nc(-c3ccncc3)no2)c1
InChIKey: SCUPKXISFBICSC-UHFFFAOYSA-N
Target: Protein kinase C alpha type (SINGLE PROTEIN), Homo sapiens
UniProt: P17252
Assay: Inhibition of human PKCalpha active using MBP as substrate after 60 mins in presence of [gamma-32]ATP by scintillation counting
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 385.43, ALogP 3.67, HBA 6, HBD 2, PSA 92.94, QED 0.5
Compound (SMILES): Oc1ccccc1OCCNCC1COCC(c2ccccc2)(c2ccccc2)O1
InChIKey: UUTWNAKPHRTMAJ-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Displacement of [3H]prazosin from recombinant human alpha-1a adrenergic receptor expressed in CHO cell membranes after 30 mins by liquid scintillation counting method
Measurement: Ki = 194.98 nM (pChEMBL 6.710000038146973)
Descriptors: MW 405.49, ALogP 3.72, HBA 5, HBD 2, PSA 59.95, QED 0.56
Compound (SMILES): C[C@@H]1CN(Cc2ccccc2)CCN1c1nc(-c2ccncn2)cc(=O)n1C
InChIKey: UHKPMPDIMPSXPN-MRXNPFEDSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 376.46, ALogP 1.95, HBA 7, HBD 0, PSA 67.15, QED 0.69
Compound (SMILES): Cc1cc(C)cc(C2CCCN2Cc2ccc(Oc3ccc(C(N)=O)cc3)c(Cl)c2)c1
InChIKey: CWSKEYSQPJILLT-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from recombinant human delta-opioid receptor expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 489.4 nM (pChEMBL 6.309999942779541)
Descriptors: MW 434.97, ALogP 6.19, HBA 3, HBD 1, PSA 55.56, QED 0.5
Compound (SMILES): CNC[C@H]1C[C@@H]1c1cc(F)ccc1OC.Cl
InChIKey: XKVNEESWADURQW-SCYNACPDSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in Flp-IN HEK293 cells assessed as induction of calcium flux measured every second for 5 mins by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 209.26, ALogP 2.16, HBA 2, HBD 1, PSA 21.26, QED 0.82
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Nc2c(Cl)c(Cl)c(Cl)c(Cl)c2Cl)cc1
InChIKey: FXLYZMGUWRWEML-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 362 nM (pChEMBL 6.440000057220459)
Descriptors: MW 463.56, ALogP 5.25, HBA 3, HBD 3, PSA 101.29, QED 0.43
Compound (SMILES): CC(=O)N1CCN(c2ccc(Nc3nccc(-c4sc(NC(C)C)nc4C)n3)nc2)CC1
InChIKey: PTKMSTJCOJHQGV-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1/cyclin B (unknown origin) in presence of [gamma-33P]-ATP by KINOMEscan assay
Measurement: Ki = 2695 nM (pChEMBL 5.570000171661377)
Descriptors: MW 452.59, ALogP 3.54, HBA 9, HBD 2, PSA 99.17, QED 0.59
Compound (SMILES): Cc1nc(N(C)C(=O)Cc2ccc(-c3ccccn3)cc2)sc1S(N)(=O)=O.O=S(=O)(O)O
InChIKey: KYTQWCYBYFPSPV-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of recombinant human Carbonic anhydrase 5B assessed as reduction in CO2 hydration preincubated for 15 mins prior to testing measured for 10 to 100 secs by stopped-flow assay
Measurement: Ki = 251 nM (pChEMBL 6.599999904632568)
Descriptors: MW 402.5, ALogP 2.37, HBA 6, HBD 1, PSA 106.25, QED 0.71
Compound (SMILES): COc1ccc2c(=O)n(-c3cccc(S(N)(=O)=O)c3)c(S)nc2c1
InChIKey: OZBDIMCBOHSMGS-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 363.42, ALogP 1.33, HBA 7, HBD 2, PSA 104.28, QED 0.54
Compound (SMILES): COc1ccc(Nc2ncnc3cc(NC(=O)CCCCCCC(=O)NO)sc23)cc1
InChIKey: GLZBZHZDNKSJEP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length recombinant human GST fused His6-tagged HDAC6 expressed in baculovirus infected High5 cells using Boc-Lys(epsilon-acetyl)-AMC as substrate measured after 3 hrs
Measurement: IC50 = 71.38 nM (pChEMBL 7.150000095367432)
Descriptors: MW 443.53, ALogP 4.23, HBA 8, HBD 4, PSA 125.47, QED 0.2
Compound (SMILES): COc1cc(CCN2CCC(O)(c3ccc(Cl)cc3)CC2)ccc1OCCCSSCCN.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: GGQVWQXOXKHXLB-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]spiperone from human D3 receptor expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 511.15, ALogP 4.98, HBA 7, HBD 2, PSA 67.95, QED 0.29
Compound (SMILES): CCCCCCCCCC[C@@H]1NC(=N)N[C@]2(CCCO2)[C@@H]1C(=O)O
InChIKey: XQIBJGYYXKVIHB-MPGHIAIKSA-N
Target: Sodium channel protein type 2 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q99250
Assay: Inhibition of Nav1.2 (unknown origin) by cell based assay
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 339.48, ALogP 3.22, HBA 3, HBD 4, PSA 94.44, QED 0.46
Compound (SMILES): O=S1(=O)CCC(CNc2cc(F)c(S(=O)(=O)Nc3nccs3)cc2Cl)C1
InChIKey: JYSRNWDCGVBURG-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 expressed in baculovirus-infected insect cells using 7-Benzoyloxy-4-trifluoromethyl coumarin substrate in presence of NADP+ by fluorescence based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 439.94, ALogP 2.58, HBA 7, HBD 2, PSA 105.23, QED 0.72
Compound (SMILES): C[C@@H](OCc1ccccc1)[C@@H]1N=C(c2ccccc2)c2ccccc2N(CCCCC(=O)NO)C1=O
InChIKey: HVOSXQKZQKPNSJ-ZBLYBZFDSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human KDAC1 using substrate A after 60 mins by fluorescence assay
Measurement: IC50 = 4550 nM (pChEMBL 5.340000152587891)
Descriptors: MW 485.58, ALogP 4.52, HBA 5, HBD 2, PSA 91.23, QED 0.25
Compound (SMILES): N[C@@H](CCP(=O)(O)C(O)c1ccc(N2CCOCC2)c([N+](=O)[O-])c1)C(=O)O
InChIKey: BWTDMGDNYYGBNJ-VPHXOMNUSA-N
Target: Metabotropic glutamate receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00222
Assay: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 403.33, ALogP 0.49, HBA 8, HBD 4, PSA 176.46, QED 0.27
Compound (SMILES): C=CC(=O)Nc1cccc(C(=O)Nc2ccc(Nc3cc(-c4[nH]c(SC)nc4C)ccn3)cc2)c1
InChIKey: BKUSJXDWGAHZNA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Affinity Biochemical interaction: (Enzyme-linked immunosorbent assays (ELISA)) EUB0000171b MAPK10
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 484.59, ALogP 5.62, HBA 6, HBD 4, PSA 111.8, QED 0.19
Compound (SMILES): O=C(O)c1cc2cc(Br)c(O)c([N+](=O)[O-])c2oc1=O
InChIKey: VCAAZFYHZJSTTA-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at GPR35 in human HT-29 cells assessed as induction of cell desensitization to 1 uM zaprinast preincubated for 1 hr followed by zaprinast stimulation measured after 8 minutes by DMR assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 330.05, ALogP 1.87, HBA 6, HBD 2, PSA 130.88, QED 0.49
Compound (SMILES): O=C(O)CC1CCC2(CCN(c3ccc(-c4nc5cc(C(F)(F)F)ccc5[nH]4)cn3)CC2)O1
InChIKey: GAFYPQKQPDKGNE-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75907
Assay: Inhibition of human DGAT1 expressed in yeast membrane fraction assessed as inhibition of triglyceride formation using diolein/oleoyl-CoA as substrate measured after 1 hr by 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin based fluorescence analysis
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 460.46, ALogP 4.64, HBA 5, HBD 2, PSA 91.34, QED 0.59
Compound (SMILES): O=C(NCC1NCCc2ccccc21)c1ccc(OC(F)(F)F)cc1
InChIKey: JLRDNRZTNLTOFD-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in HEK293 cells assessed as inhibition of forskolin-induced adenylyl cyclase-mediated cAMP accumulation after 30 mins by HTRF assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 350.34, ALogP 3.2, HBA 3, HBD 2, PSA 50.36, QED 0.89
Compound (SMILES): Cc1c(C#N)c(=O)oc2cc(OCc3ccc(F)cc3)ccc12
InChIKey: ZRFZWVIKCJMDRW-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 309.3, ALogP 3.69, HBA 4, HBD 0, PSA 63.23, QED 0.69