lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): FC(F)(F)CC1CN2CCNCc3ccc(Br)c1c32
InChIKey: SDJMEHUUEVLBHX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Partial agonist activity at 5HT2A receptor (unknown origin)
Measurement: EC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 335.17, ALogP 3.41, HBA 2, HBD 1, PSA 15.27, QED 0.85
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@@H]1CCC12CCN(CC)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: PGTVKKLHFBLXOX-XCZPVHLTSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 2328 nM (pChEMBL 5.630000114440918)
Descriptors: MW 559.76, ALogP 6.23, HBA 6, HBD 2, PSA 100.21, QED 0.24
Compound (SMILES): CCc1cccc(NC(=O)c2cc3cccc(O)c3oc2=N)c1
InChIKey: KJSIIAIZHJYKDK-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of recombinant AKR1C3 (unknown origin) assessed as reduction in S-tetralol-induced dehydrogenase activity by measuring NADPH level
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 308.34, ALogP 3.43, HBA 4, HBD 3, PSA 86.32, QED 0.69
Compound (SMILES): Cc1ccc2c3c1C(C)CN3CCNC2
InChIKey: MOBZMLUSNDWIQT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Partial agonist activity at 5HT2A receptor (unknown origin)
Measurement: EC50 = 693 nM (pChEMBL 6.159999847412109)
Descriptors: MW 202.3, ALogP 2.02, HBA 2, HBD 1, PSA 15.27, QED 0.69
Compound (SMILES): CN(C)c1cc(-c2ccncc2)c(-c2cccc3ccccc23)nn1
InChIKey: GEAPHVHHVPDTKQ-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Homo sapiens
UniProt: P48730
Assay: Inhibition of human CK1delta
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 326.4, ALogP 4.42, HBA 4, HBD 0, PSA 41.91, QED 0.56
Compound (SMILES): Nc1cccc(C(=O)N2CCN(C(=O)c3ccc(S(N)(=O)=O)cc3)CC2)c1
InChIKey: KBEVPEAJPAROJU-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 388.45, ALogP 0.51, HBA 5, HBD 2, PSA 126.8, QED 0.74
Compound (SMILES): Cc1nnc(-c2cnc3c(c2)C[C@@]2(OCCCc4ccccc4)[C@H]4Cc5ccc(O)c6c5[C@@]2(CCN4CC2CC2)[C@H]3O6)o1
InChIKey: VPJPODNUIYHZFU-XCQSDYEBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 < 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 576.7, ALogP 5.5, HBA 8, HBD 1, PSA 93.74, QED 0.27
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccccc5)cc4C[C@@]4(OCCCc5ccccn5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: LQSLTLGPDRWAJR-RXJSGBQWSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 < 0.51 nM (pChEMBL 9.291999816894531)
Descriptors: MW 571.72, ALogP 6.21, HBA 6, HBD 1, PSA 67.71, QED 0.25
Compound (SMILES): CC[C@@H](C)[C@@H](NC1CCCCC1)C(=O)N1C[C@@](C)(O)C[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: HUOMJWOJQZRJRS-SSFMOWBYSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition of factor 9a (unknown origin)
Measurement: IC50 = 7831 nM (pChEMBL 5.110000133514404)
Descriptors: MW 495.67, ALogP 3.12, HBA 6, HBD 4, PSA 120.58, QED 0.45
Compound (SMILES): Cn1cc(-c2ccc3nc(N4CCN(C5CCC5)CC4)ncc3c2)ccc1=O
InChIKey: LUZAYGLVUKAUQF-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 ODN2216-induced IFNalpha production preincubated for 30 mins followed by ODN2216 addition and measured after 20 hrs by alphaLISA
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 375.48, ALogP 2.67, HBA 6, HBD 0, PSA 54.26, QED 0.7
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: DSABUOKTPFOKMP-LBBUGJAGSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of [3H]propionyl-pNPY from human Y2 receptor expressed in CHO cells measured after 2 hrs by microbeta liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 951.15, ALogP -2.57, HBA 11, HBD 17, PSA 423.62, QED 0.02
Compound (SMILES): Cn1c(=O)c(C(=O)/C=C/c2nc3cc(F)ccc3[nH]2)c(-c2ccccc2)c2cc(Cl)ccc21
InChIKey: DQGPVLGXKRWKSL-VAWYXSNFSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of IKKbeta (unknown origin)
Measurement: IC50 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 457.89, ALogP 5.77, HBA 4, HBD 1, PSA 67.75, QED 0.27
Compound (SMILES): O=S(=O)(NC1CC1)c1ccc(-c2ccsc2)c(Nc2nc3cc(F)ccc3[nH]2)c1
InChIKey: DSIOFZXWEBFZJR-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant (unknown origin)
Measurement: IC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 428.51, ALogP 4.61, HBA 5, HBD 3, PSA 86.88, QED 0.42
Compound (SMILES): COc1cccc(C2CCN(c3ccn4c(CC5CC5)nnc4c3Cl)CC2)c1
InChIKey: YGCFJWJCTHLYIF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human 5HT2A receptor expressed in HEK293 cells assessed as inhibition of 5HT-induced intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 396.92, ALogP 4.73, HBA 5, HBD 0, PSA 42.66, QED 0.62
Compound (SMILES): O=C1c2cccc3cccc(c23)C(=O)N1CCCCCCN1CCN(c2nsc3ccccc23)CC1
InChIKey: JIKHUPCDDIJQPL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5HT7b receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 498.65, ALogP 5.43, HBA 6, HBD 0, PSA 56.75, QED 0.24
Compound (SMILES): CC[C@@H](C)[C@@H](NS(=O)(=O)Cc1ccc(Cl)cc1)C(=O)N1C[C@@](C)(O)C[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: UCIVAANSXWYOFX-WMHYTQGESA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition of factor 9a (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 602.16, ALogP 2.97, HBA 7, HBD 4, PSA 154.72, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: VSJXEJIQQOXXRQ-RSXGOPAZSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 21690 nM (pChEMBL 4.659999847412109)
Descriptors: MW 532.69, ALogP 5.72, HBA 7, HBD 1, PSA 97.56, QED 0.3
Compound (SMILES): O=C(/C=C/c1nc2ccccc2[nH]1)c1c(-c2ccccc2)c2ccccc2[nH]c1=O
InChIKey: JMHGWNZBVSPKBH-CCEZHUSRSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of IKKbeta (unknown origin)
Measurement: IC50 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 391.43, ALogP 4.97, HBA 3, HBD 2, PSA 78.61, QED 0.34
Compound (SMILES): CC(C)(C)C(=O)OCOP(=O)(OCOC(=O)C(C)(C)C)C1CCCN(O)C1=O
InChIKey: TVFIFFUSHZDTKT-UHFFFAOYSA-N
Target: Alpha-enolase (SINGLE PROTEIN), Homo sapiens
UniProt: P06733
Assay: Inhibition of ENO1 in overexpressed human D423 cells incubated for 5 days in presence of 1 % oxygen by crystal violet staining based spectrophotometry
Measurement: IC50 = 2806 nM (pChEMBL 5.550000190734863)
Descriptors: MW 423.4, ALogP 2.69, HBA 9, HBD 1, PSA 128.67, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(Cc1ccc(OC)cc1)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: TWKRUPMODSFFPO-VTIYRKAUSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 3231 nM (pChEMBL 5.489999771118164)
Descriptors: MW 637.83, ALogP 7.03, HBA 7, HBD 2, PSA 109.44, QED 0.13
Compound (SMILES): COC(=O)c1cc(C#Cc2ccc(NC(=O)C(=O)O)cc2)ccc1O
InChIKey: LDGAJCNFKHLQPY-UHFFFAOYSA-N
Target: Triple specificity protein phosphatase PtpB (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: I6WXK4
Assay: Inhibition Assay: Compounds were tested against mPTPB using the p-nitrophenyl phosphate (pNPP) assay system in a Cary 100 UV-Vis spectrophotometer by monitoring the increase in absorbance of product formed, p-nitrophenol (pNP) at 405 nm. The reaction was started by the addition of mPTPB into a final volume of 200 μL master mix containing pH 7.0 3,3-Dimethyl glutarate buffer (50.0 mM, 1 mM EDTA, 0.15M NaCl), 3.0 mM pNPP. IC50 values for each compound were determined by varying the concentration of the inhibitor at fixed concentrations of the enzyme and by fitting the dose-response data into the four-parameter logistic curve (eq 1) model of GraphPad prism 7.02, as follows. A I /A 0 =IC 50/(IC 50+[I]).The inhibition assay for these PTPs were performed under the same conditions as mPTPB except using a different pNPP concentration corresponding to the Km of the FTP studied.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 339.3, ALogP 1.6, HBA 5, HBD 3, PSA 112.93, QED 0.44
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@@H]3C[C@@H]4C[C@H]3C[C@H]4CC#N)c12
InChIKey: KGKZRAAHCZTDQA-WRWGMCAJSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 in human STAT6-bla-RA1 cells assessed as reduction in IL4-induced STAT6-signalling pre-incubated for 1 hrs before human recombinant IL4 addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 282.35, ALogP 2.6, HBA 3, HBD 2, PSA 85.33, QED 0.89
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)(F)C2)c(Cl)c1Cl)C(F)(F)F
InChIKey: KUHHYYWBAILFNI-JTQLQIEISA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 653.48, ALogP 4.33, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): CN1CC(C(=O)N[C@@H](CCCCCC(=O)c2ccon2)c2nnc(-c3ccccc3F)o2)C1
InChIKey: JMODMXNTOJTCLH-IBGZPJMESA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 900 nM (pChEMBL 6.046000003814697)
Descriptors: MW 455.49, ALogP 3.42, HBA 8, HBD 1, PSA 114.36, QED 0.35
Compound (SMILES): C[C@@H]1[C@@H]2CN(c3nc(Nc4cnn(CCO)c4)ncc3F)C[C@]12NC(=O)C1CC1
InChIKey: CCPXLRZCWWWRON-WQBCIRTESA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 in human whole blood assessed as reduction in IFNalpha-induced STAT phosphorylation by flow cytometry
Measurement: IC50 = 443 nM (pChEMBL 6.349999904632568)
Descriptors: MW 401.45, ALogP 0.9, HBA 8, HBD 3, PSA 108.2, QED 0.63
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](CC(=O)N4CC(C#N)C4)CC3)c12
InChIKey: XTZXYRVNBGBQEE-MQMHXKEQSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in human STAT5-irf1-bla TF1 cells assessed as reduction in EPO-induced STAT5-signalling pre-incubated for 1 hrs before EPO addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 353.43, ALogP 2.21, HBA 4, HBD 2, PSA 105.64, QED 0.88
Compound (SMILES): COc1ccc(C(=O)N2CCN(C(=O)c3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: WWPOKTDCKCRXAO-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 86.3 nM (pChEMBL 7.059999942779541)
Descriptors: MW 403.46, ALogP 0.94, HBA 5, HBD 1, PSA 110.01, QED 0.82
Compound (SMILES): CC[C@@H](C)[C@@H](NC1CCC(F)(F)CC1)C(=O)N1C[C@](O)(CC)C[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: QOUOKEVURQGALZ-SSFMOWBYSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition of factor 9a (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 545.68, ALogP 3.76, HBA 6, HBD 4, PSA 120.58, QED 0.38
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccccc5C5CC5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: GKIMGPIDYWEMLB-YLLCFIMHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 2.48 nM (pChEMBL 8.609999656677246)
Descriptors: MW 610.8, ALogP 7.69, HBA 5, HBD 1, PSA 54.82, QED 0.2
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5cncnc5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: XYOJXTMPYSHNJG-LMUOQGPPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 0.87 nM (pChEMBL 9.0600004196167)
Descriptors: MW 572.71, ALogP 5.6, HBA 7, HBD 1, PSA 80.6, QED 0.28
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc(C(F)(F)F)cc2Cl)cc1
InChIKey: CXXIUJZSLPZZIM-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of SHP1 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 367.71, ALogP 3.78, HBA 2, HBD 2, PSA 66.4, QED 0.6
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2cccc(C(F)(F)F)c2)cc1
InChIKey: KJCWXIZZPNBYHI-UHFFFAOYSA-N
Target: Triple specificity protein phosphatase PtpB (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: I6WXK4
Assay: Inhibition Assay: Compounds were tested against mPTPB using the p-nitrophenyl phosphate (pNPP) assay system in a Cary 100 UV-Vis spectrophotometer by monitoring the increase in absorbance of product formed, p-nitrophenol (pNP) at 405 nm. The reaction was started by the addition of mPTPB into a final volume of 200 μL master mix containing pH 7.0 3,3-Dimethyl glutarate buffer (50.0 mM, 1 mM EDTA, 0.15M NaCl), 3.0 mM pNPP. IC50 values for each compound were determined by varying the concentration of the inhibitor at fixed concentrations of the enzyme and by fitting the dose-response data into the four-parameter logistic curve (eq 1) model of GraphPad prism 7.02, as follows. A I /A 0 =IC 50/(IC 50+[I]).The inhibition assay for these PTPs were performed under the same conditions as mPTPB except using a different pNPP concentration corresponding to the Km of the FTP studied.
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 333.27, ALogP 3.13, HBA 2, HBD 2, PSA 66.4, QED 0.62
Compound (SMILES): N[C@H](c1ccccc1)c1ccc(C(=O)Nc2nc3ccc(O)cc3s2)cc1
InChIKey: WMHWSQSRVLCBCN-LJQANCHMSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human NCI-H2122 cells expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 375.45, ALogP 4.3, HBA 5, HBD 3, PSA 88.24, QED 0.5
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCC2CCCCC2)CC(=O)NC2CCC2)nn1C1CCCCC1
InChIKey: CQAKQRBCNZSQEN-VWLOTQADSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHOK1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 564.77, ALogP 6.59, HBA 6, HBD 2, PSA 94.48, QED 0.3
Compound (SMILES): FC(F)(F)c1ccc2c3c1CCN3CCNC2
InChIKey: RRUGUXQFWWMSSK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Partial agonist activity at 5HT2A receptor (unknown origin)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 242.24, ALogP 2.17, HBA 2, HBD 1, PSA 15.27, QED 0.75
Compound (SMILES): C[N+]12CCC(CC1)[C@@H](OC(=O)Nc1ccc(F)cc1-c1cccc(Cl)c1)C2.O=C[O-]
InChIKey: GLSRKSNSOOXNLR-CGRXZLHLSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Antagonist activity at muscarinic M3 receptor (unknown origin) expressed in HEK293 cells coexpressing EA tagged beta-arrestin2 assessed as inhibition of carbachol-induced beta-arrestin2 recruitment preincubated for 30 mins followed by carbachol addition and measured after 90 mins by PathHunter assay
Measurement: EC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 389.88, ALogP 4.93, HBA 2, HBD 1, PSA 38.33, QED 0.76
Compound (SMILES): CN1CCC(C(=O)N[C@@H](CCCCCC(=O)c2nccs2)c2ncc(-c3ccc(F)cc3)[nH]2)CC1
InChIKey: OEVNYXUGKVJBIX-NRFANRHFSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 497.64, ALogP 5, HBA 6, HBD 2, PSA 90.98, QED 0.29
Compound (SMILES): CN(C)S(=O)(=O)c1ccc(NCCCCCCC(=O)NO)c2nonc12
InChIKey: DKKWVGYRUAULAX-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin)
Measurement: IC50 = 15700 nM (pChEMBL 4.800000190734863)
Descriptors: MW 385.45, ALogP 1.34, HBA 8, HBD 3, PSA 137.66, QED 0.32
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](O)CC3)c12
InChIKey: CCYIACUGOTYITD-KYZUINATSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 in human STAT6-bla-RA1 cells assessed as reduction in IL4-induced STAT6-signalling pre-incubated for 1 hrs before human recombinant IL4 addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 247.3, ALogP 1.58, HBA 3, HBD 3, PSA 81.77, QED 0.72
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)CNCCCCN(CC[C@H](N)C(=O)O)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O)C(=O)N[C@@H](C)C(N)=O
InChIKey: NEGZUEBSGUQPGC-JREFTPJBSA-N
Target: N-terminal Xaa-Pro-Lys N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV86
Assay: Time dependent inhibition of NTMT1 (unknown origin) pre-incubated for 90 mins before GPKRIA peptide substrate addition by SAHH coupled fluorescence assay based Morrison's quadratic equation analysis
Measurement: Ki = 0.62 nM (pChEMBL 9.210000038146973)
Descriptors: MW 1061.26
Compound (SMILES): CC(C)Oc1ccc(F)c(-c2cnc(N)c(C(=O)Nc3cnccc3N3CCC[C@@H](C(=O)O)C3)n2)c1
InChIKey: UZIATSFXNVOVFE-OAHLLOKOSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 2482 nM (pChEMBL 5.610000133514404)
Descriptors: MW 494.53, ALogP 3.6, HBA 8, HBD 3, PSA 143.56, QED 0.45
Compound (SMILES): Cc1ccc(-c2cnc3c(c2)C[C@@]2(OCCCc4ccccc4)[C@H]4Cc5ccc(O)c6c5[C@@]2(CCN4CC2CC2)[C@H]3O6)cc1
InChIKey: XOKFAPUHFHWDFP-QJMCPCMJSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 3.63 nM (pChEMBL 8.4399995803833)
Descriptors: MW 584.76, ALogP 7.12, HBA 5, HBD 1, PSA 54.82, QED 0.22
Compound (SMILES): CC(=O)Nc1cccc(Nc2nc(Nc3ccc(N4CCN(C)CC4)cn3)ncc2Cl)c1
InChIKey: GVJLKAACQAJVQS-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Binding affinity to recombinant full-length GFP-fused CDK9/His-tagged cyclin T1 (unknown origin) expressed in HEK293T cells measured after 30 mins by microscale thermophoresis method
Measurement: Kd = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 452.95, ALogP 3.72, HBA 8, HBD 3, PSA 98.31, QED 0.52
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)CNCCCN(CC[C@H](N)C(=O)O)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O)C(=O)N[C@@H](C)C(N)=O
InChIKey: JQDSWQNMLLRDDE-FEZLTFFESA-N
Target: N-terminal Xaa-Pro-Lys N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV86
Assay: Time dependent inhibition of NTMT1 (unknown origin) pre-incubated for 90 mins before GPKRIA peptide substrate addition by SAHH coupled fluorescence assay based Morrison's quadratic equation analysis
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 1047.23
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(CC(C)(C)C(=O)O)nc2CC2CCC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: BNMRBSLYMNBOOG-NSHDSACASA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Binding affinity to recombinant human RORbeta transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 1267 nM (pChEMBL 5.900000095367432)
Descriptors: MW 573.49, ALogP 6.34, HBA 5, HBD 2, PSA 96.36, QED 0.37
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(SCc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: COGUZYALRYMQTD-LJQANCHMSA-N
Target: CDK3/Cyclin E (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of kinase tracer 236 binding to recombinant human full-length N-terminal GST-tagged CDK3/cyclin E1 expressed in baculovirus expression system measured after 1 hr by LanthaScreen Eu Kinase Binding Assay
Measurement: IC50 = 366 nM (pChEMBL 6.440000057220459)
Descriptors: MW 525.7, ALogP 5.56, HBA 8, HBD 2, PSA 100.36, QED 0.29
Compound (SMILES): Cc1nc2c(-c3nnc[nH]3)cc(-c3ccnc(C#N)c3)cc2n1-c1ccnc2c(F)ccc(F)c12
InChIKey: XEFPRVONPORJSI-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length p110alpha/p85alpha using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 = 346 nM (pChEMBL 6.460000038146973)
Descriptors: MW 464.44, ALogP 4.88, HBA 7, HBD 1, PSA 108.96, QED 0.4
Compound (SMILES): C[C@@H]1COCCN1c1cc(-c2ccnn2C)c2ccnc(-c3ccn[nH]3)c2n1
InChIKey: YBXRSCXGRPSTMW-CYBMUJFWSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK (unknown origin)
Measurement: IC50 = 332 nM (pChEMBL 6.480000019073486)
Descriptors: MW 375.44, ALogP 2.65, HBA 7, HBD 1, PSA 84.75, QED 0.59
Compound (SMILES): C[N+](C)(C)C[C@@H]1CO[C@@H](c2ccccc2)[C@H](c2ccccc2)O1.[I-]
InChIKey: HERDQXDYIAMKFW-SFZWVAMRSA-M
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 4570.88 nM (pChEMBL 5.340000152587891)
Descriptors: MW 312.43, ALogP 3.59, HBA 2, HBD 0, PSA 18.46, QED 0.8
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccc(OC)c(OC)c4)c(C)c3c2)CC1
InChIKey: SPKQTQHGAWZQEL-UHFFFAOYSA-N
Target: Toll-like receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00206
Assay: Antagonist activity at human TLR4 overexpressed in HEK-Blue cells assessed as inhibition of LPD-RK induced NFkappaB and AP-1 activation preincubated for 30 mins followed by LPD-RK stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 14970 nM (pChEMBL 4.829999923706055)
Descriptors: MW 407.56, ALogP 4.56, HBA 4, HBD 2, PSA 49.52, QED 0.6
Compound (SMILES): CCC(=O)CNC(=O)C[C@H](CCC1CCCCC1)NC(=O)c1cc(-c2c(OC)cccc2OC)n(CC(C)C)n1
InChIKey: YYWOPNXJOZHZIU-QHCPKHFHSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHOK1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 554.73, ALogP 5.17, HBA 7, HBD 2, PSA 111.55, QED 0.31
Compound (SMILES): Cc1cc(-c2cc(-c3nnc[nH]3)c3nc(C)n(-c4ccnc5c(F)ccc(F)c45)c3c2)cc(N)n1
InChIKey: VMTLHCPUBQTEFH-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00459
Assay: TR-FRET Assay: Class I PI3K isoforms were expressed and purified as heterodimeric recombinant proteins. All assay reagents and buffers for the TR-FRET assay were purchased from Millipore. PI3K isoforms were assayed under initial rate conditions in the presence of 25 mM Hepes (pH 7.4), and 2× Km ATP (75-500 μM), 2 μM PIP2, 5% glycerol, 5 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, and 1% (v/v) DMSO at the following concentrations for each isoform: PI3Kα, PI3Kβ, and PI3Kδ between 25 and 50 pM, and PI3Kγ at 2 nM. The compounds were added to the assay solution and incubated for 30 minutes at 25° C. The reactions were terminated with a final concentration of 10 mM EDTA, 10 nM labeled-PIPS, and 35 nM Europium labeled GRP-1 detector protein before reading TR-FRET on an Envision plate reader (Ex: 340 nm; Em: 615/665 nm; 100 μs delay and 500 μs read window).
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 468.47, ALogP 4.9, HBA 7, HBD 2, PSA 111.19, QED 0.38
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(CC(C)(C)C(=O)O)nc2CC2CCC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: VICVDIVPAGQTTO-INIZCTEOSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Binding affinity to RORbeta (unknown origin) assessed as dissociation constant by thermal shift binding assay
Measurement: Kd = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 587.51, ALogP 6.73, HBA 5, HBD 2, PSA 96.36, QED 0.32
Compound (SMILES): CC1(C)COc2c(COc3ccccc3CC(=O)O)cc(-c3ccc4c(c3)[C@H](N)CCO4)cc21
InChIKey: ZDMYKWNIEWNTLR-HSZRJFAPSA-N
Target: Coagulation factor VII (SINGLE PROTEIN), Homo sapiens
UniProt: P08709
Assay: Inhibition of human F7a using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 75000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 459.54, ALogP 5.01, HBA 5, HBD 2, PSA 91.01, QED 0.54
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCC2CCCCC2)CC(=O)NC2CCC2)nn1C1CCCC1
InChIKey: LOYFGOQECXZGSS-DEOSSOPVSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHOK1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 550.74, ALogP 6.2, HBA 6, HBD 2, PSA 94.48, QED 0.33
Compound (SMILES): CC(C)c1cc(CCOc2ccccc2C(=O)O)cc(-c2ccc3c(c2)[C@H](N)CO3)c1
InChIKey: RHEKWNPDSIWZKZ-HSZRJFAPSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human F10a using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 417.51, ALogP 5.19, HBA 4, HBD 2, PSA 81.78, QED 0.55
Compound (SMILES): CC(C)c1cc(-c2ccc3c(c2)[C@H](N)CO3)cc(C(O)Cn2ccc3cccc(C(=O)O)c32)c1
InChIKey: GOERAAJVARXHDP-IKOFQBKESA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human F10a using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 456.54, ALogP 5.26, HBA 5, HBD 3, PSA 97.71, QED 0.37
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CN(S(=O)(=O)c4ccccc4)C[C@@H]3C(=O)N[C@H]3CCCNC3)cc2c1
InChIKey: YCZKMQXSVCMJPL-PTLVVNQVSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 509.63, ALogP 1.76, HBA 5, HBD 4, PSA 123.4, QED 0.4
Compound (SMILES): CCc1[nH]nc2[nH]c(=O)cc(C3CCCCC3)c12
InChIKey: KDOGGCVUVDIMJL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in human STAT5-irf1-bla TF1 cells assessed as reduction in EPO-induced STAT5-signalling pre-incubated for 1 hrs before EPO addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 245.33, ALogP 2.86, HBA 2, HBD 2, PSA 61.54, QED 0.85
Compound (SMILES): CCCCCCC(C)(C)c1cc(OC)cc(OCCCCCCCC(=O)NC2CC2)c1
InChIKey: CWNFRGKJPKDJSQ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Activation of human TRPV1 expressed in HEK293 cells assessed as calcium influx preincubated for 5 mins by Fluo-4AM dye based fluorescence assay
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 431.66, ALogP 6.94, HBA 3, HBD 1, PSA 47.56, QED 0.27
Compound (SMILES): CCC(O)CNC(=O)C[C@H](CCC1CCCCC1)NC(=O)c1cc(-c2c(OC)cccc2OC)n(CC(C)C)n1
InChIKey: PEYDBQHSYMRJSL-UXMRNZNESA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Displacement of [125I]-apelin-13 from human APJ receptor stably expressed in CHOK1 cell membrane measured after 2 hrs by topcount scintillation counting method
Measurement: Ki = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 556.75, ALogP 4.96, HBA 7, HBD 3, PSA 114.71, QED 0.29
Compound (SMILES): O=C(Nc1ccc(F)cc1-c1cccc(Cl)c1)O[C@H]1CN2CCC1CC2
InChIKey: OUUOAZNFNHOROT-IBGZPJMESA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Antagonist activity at muscarinic M3 receptor (unknown origin) expressed in HEK293 cells coexpressing EA tagged beta-arrestin2 assessed as inhibition of carbachol-induced beta-arrestin2 recruitment preincubated for 30 mins followed by carbachol addition and measured after 90 mins by PathHunter assay
Measurement: EC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 374.84, ALogP 4.79, HBA 3, HBD 1, PSA 41.57, QED 0.84
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(OC4CCNCC4)cc3)c2C)cc(OC)c1OC
InChIKey: IGWDSVRQGPGZSY-UHFFFAOYSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: Inhibition of human ALK4 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay
Measurement: IC50 = 1363 nM (pChEMBL 5.869999885559082)
Descriptors: MW 434.54, ALogP 4.88, HBA 6, HBD 1, PSA 61.84, QED 0.57
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc4c(c3)B(O)OCC4)ncc2C(F)(F)F)c1
InChIKey: ZSNQHZKOLDPDCV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human His-tagged full length BTK expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 469.23
Compound (SMILES): O=C(CCCCCc1ccccc1)N[C@H]1CC[C@H](O)CC1
InChIKey: SUKXKLNDBLNTSW-QAQDUYKDSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 289.42, ALogP 3.21, HBA 2, HBD 2, PSA 49.33, QED 0.76
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(NC(=O)CC(C)(C)O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: UWXKJQJLCPNMJD-NSHDSACASA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 649.52, ALogP 5.02, HBA 7, HBD 3, PSA 128.7, QED 0.34
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: JOCZLXXGQVICFM-NSHDSACASA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 667.51, ALogP 4.72, HBA 7, HBD 3, PSA 128.7, QED 0.35
Compound (SMILES): COc1cccc(C(=O)O)c1OCCc1cc(-c2ccc3c(c2)[C@H](N)CO3)cc(C(C)C)c1
InChIKey: KXSZMPGKDDBJRE-HSZRJFAPSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 9090 nM (pChEMBL 5.039999961853027)
Descriptors: MW 447.53, ALogP 5.2, HBA 5, HBD 2, PSA 91.01, QED 0.49
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCCC[C@@H]2C)c(C(F)F)c1F)C(F)(F)F
InChIKey: GKQSHKLDFZHZNL-BBRMVZONSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 658.69, ALogP 5.02, HBA 7, HBD 3, PSA 128.7, QED 0.31
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: OFTCQOAUGKRHIY-GKXKVECMSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4R expressed in HEK293T cells co-expressing ARRB2 assessed as induction of beta-arrestin2 recruitment measured for 40 mins by D-luciferin based luminescence assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 678.8, ALogP -1.55, HBA 8, HBD 13, PSA 316.23, QED 0.04
Compound (SMILES): C=CC(=O)NCCOc1cc(Cc2ccccc2)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: DHHJVKCNCRIXRE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 486.52, ALogP 5.92, HBA 3, HBD 3, PSA 82.8, QED 0.18
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3ccccc3[N+](=O)[O-])CC2)cc1
InChIKey: FVKDIKUTAQWUAI-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human CA14 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 61.6 nM (pChEMBL 7.210000038146973)
Descriptors: MW 418.43, ALogP 0.84, HBA 6, HBD 1, PSA 143.92, QED 0.58
Compound (SMILES): COc1cccc(SC[C@@H]2CCc3cc([C@H]4CC[C@](N)(COP(=O)(O)O)C4)ccc3C2)c1
InChIKey: LMYHLCLZWOIUDH-QATBIIFWSA-N
Target: Sphingosine-1-phosphate lyase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95470
Assay: Receptor [35S] GTPgammaS Binding Assays: (S1P1 GTPgammaS/S1P3 GTPgammaS): Compounds were loaded in a 384 Falcon v-bottom plate (0.5 l/well in a 11 point, 3-fold dilution). Membranes prepared from S1P1/CHO cells or EDG3-Gal5-bla HEK293T cells (EDG3 equivalent S1P3) were added to the compound plate (40 l/well, final protein 3 μg/well) with MULTIDROP®. [35S]GTP (1250 Ci/mmol, Perkin Elmer) was diluted in assay buffer: 20 mM HEPES, pH7.5, 10 mM MgCl2, 150 mM NaCl, 1 mM EGTA (ethylene glycol tetraacetic acid), 1 mM DTT (Dithiothreitol), 10 μM GDP, 0.1% fatty acid free BSA, and 10 μg/ml Saponin to 0.4 nM. 40 μl of the [35S] GTP solution was added to the compound plate with a final concentration of 0.2 nM. The reaction was kept at room temperature for 45 min. At the end of incubation, all the mixtures in the compound plate were transferred to Millipore 384-well FB filter plates via the VELOCITY11® Vprep liquid handler. The filter plate was washed with water 4 times by using the manifold Embla plate washer and dried at 60° C. for 45 min. MicroScint 20 scintillation fluid (30 μl) was added to each well for counting on the Packard TOPCOUNT®. EC50 is defined as the agonist concentration that corresponds to 50% of the Ymax (maximal response) obtained for each individual compound tested. The EC50 for Example 689 was determined to be 5.7 nM in the assay utilizing membranes prepared from S1P1/CHO cells. The EC50 for Example 689 was determined to be >2000 nM in the assay utilizing membranes prepared from EDG3-Gal5-bla HEK293T cells.A smaller value for GTPγS S1P1 EC50 value indicated greater activity for the compound in the GTPγS S1P1 binding assay. A larger value for the GTPγS S1P3 EC50 value indicated less activity in the GTPγS S1P3 binding assay. Example 689, which is the phosphate ester of Example 672, possessed activity as an agonist of S1P1 and is selective over S1P3. Example 697, which is the phosphate ester of Example 681, possessed activity as an agonist of S1P1 and is selective over S1P3. Thus the compounds of the present invention may be used in treating, preventing, or curing various S1P1 receptor-related conditions while reducing or minimizing the side effects due to S1P3 activity. The selectivity of the compounds of the present invention indicate their potential use in treating, preventing, or curing autoimmune and inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, lupus, psoriasis, or vascular diseases, while reducing or minimizing possible side effects due to S1P3 activity. Other potential uses of the compounds of the present invention include minimizing or reducing rejection of transplanted organs, while reducing or minimizing side effects due to S1P3 activity.
Measurement: EC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 477.56, ALogP 4.67, HBA 5, HBD 3, PSA 102.01, QED 0.38
Compound (SMILES): c1cc2c3c(c1)CNCCN3CCC2
InChIKey: BBFXEOWPELWKIY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2A receptor (unknown origin)
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 188.27, ALogP 1.54, HBA 2, HBD 1, PSA 15.27, QED 0.66
Compound (SMILES): CC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1
InChIKey: QWEBSYDRFXZQMF-GHIUXRNCSA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of human 20S proteasome LMP2 activity in human RPMI-8226 cells overexpressing ABCB1 using Ac-PAL-AMC as fluorogenic substrate incubated for 72 hrs by fluorescence assay
Measurement: IC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 514.62, ALogP 0.73, HBA 6, HBD 3, PSA 137.21, QED 0.35
Compound (SMILES): CC(C)c1cc(-c2ccc3c(c2)[C@H](N)CO3)cc(C(O)CN2CCc3cccc(C(=O)O)c32)c1
InChIKey: PKASBNFVFWUNOA-IKOFQBKESA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 6140 nM (pChEMBL 5.210000038146973)
Descriptors: MW 458.56, ALogP 4.66, HBA 5, HBD 3, PSA 96.02, QED 0.5
Compound (SMILES): Nc1ncnc2c1c(Oc1cc(C(F)(F)F)ccn1)nn2[C@@H]1CCCC[C@H]1O
InChIKey: QBGXAQUTKHIMNE-GHMZBOCLSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins by LC-MS/MS analysis
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 394.36, ALogP 3.09, HBA 8, HBD 2, PSA 111.97, QED 0.7
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCCN2CCN(c3cccc(C)c3C)CC2)c(=O)c2cc(F)ccc12
InChIKey: XFZRXHPMALBAIJ-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Displacement of [3H]imipramine from SERT receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 537.64, ALogP 2.93, HBA 8, HBD 1, PSA 96.77, QED 0.4
Compound (SMILES): CC/C(=C\c1ccccc1)[C@@H]1C[C@H]1NC1CC2(C1)CN(CCO)C2
InChIKey: XOLYNCLYMBLPIW-ZVIVXHKUSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Time dependant inhibition of recombinant N-terminal His-tagged LSD1 (unknown origin) expressed in Escherichia coli expression system assessed as inhibitory constant using ART-K(Me1)-QTARKSTGGKAPRKQLAGGK(Biotin) as substrate incubated for 60 mins by TR-FRET assay
Measurement: Ki = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 326.48, ALogP 2.91, HBA 3, HBD 2, PSA 35.5, QED 0.81
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccccc5)cc4C[C@@]4(OCCCC5CCCCC5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: GWROYBPWASJEAK-RJKGWOMYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO cell membranes incubated for 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 576.78, ALogP 7.54, HBA 5, HBD 1, PSA 54.82, QED 0.28
Compound (SMILES): CS(=O)(=O)n1cc2c(n1)CN([C@@H]1C[C@H](N)[C@@H](c3cc(F)ccc3F)O[C@@H]1C(F)(F)F)C2
InChIKey: GUBOXFWNNXSQNH-SVGFKBNWSA-N
Target: Cytochrome P450 2E1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05181
Assay: Inhibition of recombinant human CYP2E1
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 466.43, ALogP 2.07, HBA 7, HBD 1, PSA 90.45, QED 0.7
Compound (SMILES): O=C(O)c1cc(-c2ccc(C34CCN(CC3)CC4)cc2)cc(-n2cc(-c3ccc(C(F)(F)F)cc3)nn2)c1
InChIKey: KWMPBNRKPTVPTE-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 518.54, ALogP 6.06, HBA 5, HBD 1, PSA 71.25, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CCNC(=S)Nc1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(=O)N[C@@H](CCCC[N+](C)(C)C)C(=O)N[C@@H](CO)C(N)=O
InChIKey: SLIIQFIECPRWSD-KPZWOUCOSA-O
Target: Chromobox protein homolog 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC52
Assay: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis
Measurement: Kd = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 1067.26
Compound (SMILES): Oc1ccc(C2CCN(c3ccn4c(CC5CC5)nnc4c3Cl)CC2)cc1
InChIKey: QYXZTBGZHFSRNA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human 5HT2A receptor expressed in HEK293 cells assessed as inhibition of 5HT-induced intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: IC50 = 724.44 nM (pChEMBL 6.139999866485596)
Descriptors: MW 382.9, ALogP 4.42, HBA 5, HBD 1, PSA 53.66, QED 0.73
Compound (SMILES): FC(F)(F)CC1CN2CCNCc3ccc(Br)c1c32
InChIKey: SDJMEHUUEVLBHX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2A receptor (unknown origin)
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 335.17, ALogP 3.41, HBA 2, HBD 1, PSA 15.27, QED 0.85
Compound (SMILES): CCc1cccc(NC(=O)c2cc3cccc(O)c3oc2=N)c1
InChIKey: KJSIIAIZHJYKDK-UHFFFAOYSA-N
Target: Carbonyl reductase [NADPH] 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P16152
Assay: Inhibition of CBR1 (unknown origin)
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 308.34, ALogP 3.43, HBA 4, HBD 3, PSA 86.32, QED 0.69
Compound (SMILES): Cc1ccc2c3c1C(C)CN3CCNC2
InChIKey: MOBZMLUSNDWIQT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2A receptor (unknown origin)
Measurement: Ki = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 202.3, ALogP 2.02, HBA 2, HBD 1, PSA 15.27, QED 0.69
Compound (SMILES): Nc1cccc(C(=O)N2CCN(C(=O)c3ccc(S(N)(=O)=O)cc3)CC2)c1
InChIKey: KBEVPEAJPAROJU-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human CA14 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 91.7 nM (pChEMBL 7.039999961853027)
Descriptors: MW 388.45, ALogP 0.51, HBA 5, HBD 2, PSA 126.8, QED 0.74
Compound (SMILES): CC[C@@H](C)[C@@H](NC1CCCCC1)C(=O)N1C[C@@](C)(O)C[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: HUOMJWOJQZRJRS-SSFMOWBYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 218 nM (pChEMBL 6.659999847412109)
Descriptors: MW 495.67, ALogP 3.12, HBA 6, HBD 4, PSA 120.58, QED 0.45
Compound (SMILES): O=S(=O)(NC1CC1)c1ccc(-c2ccsc2)c(Nc2nc3cc(F)ccc3[nH]2)c1
InChIKey: DSIOFZXWEBFZJR-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R172K mutant (unknown origin)
Measurement: IC50 = 78800 nM (pChEMBL 4.099999904632568)
Descriptors: MW 428.51, ALogP 4.61, HBA 5, HBD 3, PSA 86.88, QED 0.42
Compound (SMILES): COc1cccc(C2CCN(c3ccn4c(CC5CC5)nnc4c3Cl)CC2)c1
InChIKey: YGCFJWJCTHLYIF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human 5HT2A receptor expressed in HEK293 cells assessed as inhibition of 5HT-induced intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: IC50 = 4168.69 nM (pChEMBL 5.380000114440918)
Descriptors: MW 396.92, ALogP 4.73, HBA 5, HBD 0, PSA 42.66, QED 0.62
Compound (SMILES): CC[C@@H](C)[C@@H](NS(=O)(=O)Cc1ccc(Cl)cc1)C(=O)N1C[C@@](C)(O)C[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: UCIVAANSXWYOFX-WMHYTQGESA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 602.16, ALogP 2.97, HBA 7, HBD 4, PSA 154.72, QED 0.28
Compound (SMILES): O=C(/C=C/c1nc2ccccc2[nH]1)c1c(-c2ccccc2)c2ccccc2[nH]c1=O
InChIKey: JMHGWNZBVSPKBH-CCEZHUSRSA-N
Target: Protein-arginine deiminase type-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM07
Assay: Inhibition Assay: Assay buffer (as aforementioned): 100 mM Tris-HCl (pH 7.6), 2 mM DTT, 1 mM CaCl2Final concentrations:100 nM hPAD4 enzyme50 μM (8-fold sub-Km) substrate peptide0.5% DMSOTotal incubation time: 65 mins at 37° C.Stop solution: 40 μl 5% TCA in ACN0.25 μL of compound solution was added to 10 μL of 200 nM PAD4 in assay buffer (100 mM Tris-HCl pH 7.6, 2 mM DTT). After 5 mins, 10 μL of 100 μM of substrate in buffer (100 mM Tris-HCl pH 7.6, 2 mM DTT, 2 mM CaCl2) was added and the reaction incubated for 60 mins at 37° C. The enzymatic reaction was quenched by addition of 40 μl of 5% TCA in ACN (1.7% TCA final concentration) stop solution. Arginine containing substrate and citrulline containing product (+1 Da mass shift) were subjected to solid phase extraction on Agilent RapidFire (RF) 300 system and detected on a coupled, triple quadrupole Agilent 6460 QQQ mass spectrometry (MS) device under application of multiple reaction monitoring (MRM) for quantitation.
Measurement: IC50 = 70000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 391.43, ALogP 4.97, HBA 3, HBD 2, PSA 78.61, QED 0.34