lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccccc2)cc1
InChIKey: BOQIBRQHNFTPDW-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: Binding affinity to human FP receptor by competitive binding assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.49, ALogP 3.21, HBA 4, HBD 1, PSA 70.08, QED 0.74
Compound (SMILES): Cn1c(C2CC2)nc2ccc(-n3ccc(OCc4ccc(Cl)s4)cc3=O)cc21
InChIKey: RPFBZAHRSRZYGF-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Antagonist activity at human MCHR1 expressed in CHO cells assessed as change in MCH(4 to 19)-stimulated Ca2+ concentration by Ca2+ mobilization assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 411.91, ALogP 4.9, HBA 6, HBD 0, PSA 49.05, QED 0.47
Compound (SMILES): Cn1c(C2CC2)nc2ccc(-n3ccc(OCc4ccc(C(F)(F)F)s4)cc3=O)cc21
InChIKey: NUGRQANZYOOAIA-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Antagonist activity at human MCHR1 expressed in CHO cells assessed as change in MCH(4 to 19)-stimulated Ca2+ concentration by Ca2+ mobilization assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 445.47, ALogP 5.26, HBA 6, HBD 0, PSA 49.05, QED 0.42
Compound (SMILES): Cc1c2cc(-n3ccc(OCc4ccc(Cl)cc4)cc3=O)ccc2nn1C1CC1
InChIKey: NLQGIADBJJOEFQ-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Antagonist activity at human MCHR1 expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ mobilization measured every 2 secs by fluorometric analysis
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 405.89, ALogP 5.06, HBA 5, HBD 0, PSA 49.05, QED 0.47
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)N(Cc1ccccc1OC1CCOCC1)c1cc(F)ccc1F
InChIKey: NMZBOFGYKWSRMA-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Inhibition of human gamma-secretase expressed in CHO cells assessed as suppression of amyloid beta 42 production using C100-Flag as substrate incubated for 4 hrs by ELISA
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 477.5, ALogP 5.06, HBA 4, HBD 0, PSA 55.84, QED 0.48
Compound (SMILES): CCC(CC)N(Cc1ccc(C(=O)O)cc1)S(=O)(=O)c1ccc(Cl)cc1
InChIKey: YAGYWQLXJIWAKJ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Inhibition of gamma secretase (unknown origin)-mediated amyloid beta (1 to 40) production by cell based assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 395.91, ALogP 4.42, HBA 3, HBD 1, PSA 74.68, QED 0.72
Compound (SMILES): O=C1OCc2cc(CCN3CCN(C(=O)Cc4ccc(-n5cnnn5)nc4)CC3)ccc21
InChIKey: DSTPQJIKZPOBFY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]-MK499 from human ERG expressed in HEK293 cells
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 433.47, ALogP 0.66, HBA 9, HBD 0, PSA 106.34, QED 0.52
Compound (SMILES): O=C1OCc2cc(CCC3CCN(C(=O)Cc4ccc(-n5cnnn5)nc4)CC3)ccc21
InChIKey: GEROKZRQGOYQDR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]-MK499 from human ERG expressed in HEK293 cells
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 432.48, ALogP 2.14, HBA 8, HBD 0, PSA 103.1, QED 0.55
Compound (SMILES): Cc1cc(-n2cnnn2)cnc1CC(=O)N1CCN(CCc2ccc3c(c2C)COC3=O)CC1
InChIKey: RZUWLMYXOXGJLS-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of human ROMK expressed in CHO cells by whole-cell voltage clamp method
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 461.53, ALogP 1.27, HBA 9, HBD 0, PSA 106.34, QED 0.51
Compound (SMILES): Cc1c(C(C)CN2CCN(C(=O)Cc3ccc(-n4cnnn4)nc3)CC2)ccc2c1COC2=O
InChIKey: JNXIDSMXBWTVGA-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of human ROMK expressed in CHO cells by whole-cell voltage clamp method
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 461.53, ALogP 1.53, HBA 9, HBD 0, PSA 106.34, QED 0.51
Compound (SMILES): Cc1c(C(F)CN2CCN(C(=O)Cc3ccc(-n4cnnn4)nc3)CC2)ccc2c1COC2=O
InChIKey: IWPLBAYOPYISRO-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of human ROMK expressed in CHO cells by whole-cell voltage clamp method
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 465.49, ALogP 1.43, HBA 9, HBD 0, PSA 106.34, QED 0.5
Compound (SMILES): NNc1nccc(C(=O)O)n1
InChIKey: AVMDBCMWSSIKTF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of KDM5A (unknown origin) using substrate peptide/ascorbate/2-OG/ Fe(2) as substrate preincubated for 15 mins followed by addition of substrate peptide/ ascorbate/2-OG/ Fe(2) measured after 1 hr by AlphaLISA method
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 154.13, ALogP -0.54, HBA 5, HBD 3, PSA 101.13, QED 0.39
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccc3c(c2)OCO3)cc1.Cl.O
InChIKey: GHJOTLLQCTXWNP-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Binding affinity to human EP4 receptor
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 440.5, ALogP 2.94, HBA 6, HBD 1, PSA 88.54, QED 0.68
Compound (SMILES): CCCSc1nc(N[C@@H]2C[C@H]2c2ccccc2)c2nnn([C@@H]3C[C@H](c4nnn[nH]4)[C@@H](O)[C@H]3O)c2n1
InChIKey: SAVVNOCOOLKEPU-SSDGSGIASA-N
Target: P2Y purinoceptor 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H244
Assay: Displacement of [3H]-2-MeS-ADP from human P2Y12 assessed as inhibition constant incubated for 30 mins
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 494.59, ALogP 1.65, HBA 12, HBD 4, PSA 163.44, QED 0.21
Compound (SMILES): CCOC(=O)N1CCN(C(=O)[C@H](CCC(=O)O)NC(=O)c2cc(OC(C)(C)C(=O)O)c3ccc(C)cc3n2)CC1
InChIKey: MCBLPJPMVOVJCO-SFHVURJKSA-N
Target: P2Y purinoceptor 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H244
Assay: Antagonist activity at P2Y12 receptor in human washed platelets assessed as inhibition of ADP-induced platelet aggregation measured for 5 mins by light transmission analysis
Measurement: IC50 = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 558.59, ALogP 2.05, HBA 8, HBD 3, PSA 175.67, QED 0.39
Compound (SMILES): Fc1ccc2c(c1)c1[nH]ncc1n2-c1cccnc1
InChIKey: BPCCTTNRJCTGHS-UHFFFAOYSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of recombinant full-length human MetAP2 catalytic domain (110 to 478 residues) expressed in baculovirus using Met-AMC as substrate by fluorescence plate reader
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 252.25, ALogP 3.04, HBA 3, HBD 1, PSA 46.5, QED 0.57
Compound (SMILES): Fc1cc2c3[nH]ncc3n(-c3cccnc3)c2cc1F
InChIKey: PEWYGTLRHLRPDV-UHFFFAOYSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of recombinant full-length human MetAP2 catalytic domain (110 to 478 residues) expressed in baculovirus using Met-AMC as substrate by fluorescence plate reader
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 270.24, ALogP 3.18, HBA 3, HBD 1, PSA 46.5, QED 0.58
Compound (SMILES): Clc1ccc2c3[nH]ncc3n(-c3cccnc3)c2c1
InChIKey: LMOBUEBHMONFLE-UHFFFAOYSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of recombinant full-length human MetAP2 catalytic domain (110 to 478 residues) expressed in baculovirus using Met-AMC as substrate by fluorescence plate reader
Measurement: IC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 268.71, ALogP 3.56, HBA 3, HBD 1, PSA 46.5, QED 0.57
Compound (SMILES): Cc1nc2[nH]cnc2cc1-n1c2ccc(F)cc2c2[nH]ncc21
InChIKey: BGVWCIRYUNODHW-UHFFFAOYSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of recombinant full-length human MetAP2 catalytic domain (110 to 478 residues) expressed in baculovirus using Met-AMC as substrate by fluorescence plate reader
Measurement: IC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 306.3, ALogP 3.23, HBA 4, HBD 2, PSA 75.18, QED 0.5
Compound (SMILES): Cc1c(-n2c3ccc(F)cc3c3[nH]ncc32)cnc2[nH]cnc12
InChIKey: RRCNPYRCOUOTDZ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in Escherichia coli DH5alpha
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 306.3, ALogP 3.23, HBA 4, HBD 2, PSA 75.18, QED 0.5
Compound (SMILES): Cc1nc2c(cc1-n1c3ccc(F)cc3c3[nH]ncc31)ncn2C
InChIKey: IUZBXISRROMZSL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in Escherichia coli DH5alpha
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 320.33, ALogP 3.24, HBA 5, HBD 1, PSA 64.32, QED 0.52
Compound (SMILES): O=C(NCCO)c1ccc(-n2c3ccc(F)cc3c3[nH]ncc32)cc1
InChIKey: RZXSROGFHJQWNH-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in Escherichia coli DH5alpha
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 338.34, ALogP 2.37, HBA 4, HBD 3, PSA 82.94, QED 0.53
Compound (SMILES): Cc1cc(C(=O)NCCO)ccc1-n1c2ccc(F)cc2c2[nH]ncc21
InChIKey: OTERKSQZXOAQLU-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in Escherichia coli DH5alpha
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 352.37, ALogP 2.68, HBA 4, HBD 3, PSA 82.94, QED 0.53
Compound (SMILES): Nc1ncc(-n2c3ccc(F)cc3c3[nH]ncc32)cc1Cl
InChIKey: PYSBUBPDECGJSZ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in Escherichia coli DH5alpha
Measurement: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 301.71, ALogP 3.28, HBA 4, HBD 2, PSA 72.52, QED 0.57
Compound (SMILES): CNc1nc(Nc2cnn(C(CC(N)=O)C3CCCCC3)c2)ncc1C(F)(F)F
InChIKey: ZSFCHNZEXNPWHH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human recombinant JAK3 assessed as reduction in Ulight-CAGAGAIETDKEYYTVKD phosphorylation pre-incubated before substrate addition and measured after 60 mins by LANCE detection method
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 411.43, ALogP 3.47, HBA 7, HBD 3, PSA 110.75, QED 0.64
Compound (SMILES): CCS(=O)(=O)Oc1ccc(NC(=O)C2CCCCC2)cc1
InChIKey: OANARLBVDCTXGB-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14638
Assay: Inhibition of human NPP3 expressed in African green monkey COS7 cell membranes pre-incubated for 10 mins before pNP-TMP substrate addition and further incubated for 15 mins by colorimetric method
Measurement: IC50 = 369 nM (pChEMBL 6.429999828338623)
Descriptors: MW 311.4, ALogP 2.93, HBA 4, HBD 1, PSA 72.47, QED 0.85
Compound (SMILES): Cc1ccc(S(=O)(=O)Oc2ccc(NC(=O)C3CCCC3)cc2)cc1
InChIKey: IPQFASYJHPSAIH-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14638
Assay: Inhibition of human NPP3 expressed in African green monkey COS7 cell membranes pre-incubated for 10 mins before pNP-TMP substrate addition and further incubated for 15 mins by colorimetric method
Measurement: IC50 = 856 nM (pChEMBL 6.070000171661377)
Descriptors: MW 359.45, ALogP 3.89, HBA 4, HBD 1, PSA 72.47, QED 0.82
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccn5)c4C(F)(F)F)n3)cc2)C1
InChIKey: UISONOSIQKJKKZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 471.4, ALogP 3.99, HBA 8, HBD 1, PSA 118.38, QED 0.45
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp method
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44
Compound (SMILES): O=C(CCCc1csc(/C=C/c2ccccc2)n1)NO
InChIKey: HJPIJALRLZVGMS-MDZDMXLPSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of human recombinant HDAC10 using RHK-K(Ac)-AMC as substrate
Measurement: IC50 = 78310 nM (pChEMBL 4.110000133514404)
Descriptors: MW 288.37, ALogP 3.14, HBA 4, HBD 2, PSA 62.22, QED 0.63
Compound (SMILES): O=c1c(Cc2ccncc2)coc2ccccc12
InChIKey: CKGJGNLNAFKOLX-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human CYP17 expressed in Escherichia coli co-transfected with rat NADPH-P450 reductase using progesterone as substrate for 30 mins measured as formation of 17alpha-hydroxyprogesterone and 16alpha-hydroxyprogesterone in presence of NADPH
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 237.26, ALogP 2.78, HBA 3, HBD 0, PSA 43.1, QED 0.69
Compound (SMILES): O=c1c(Cc2ccncc2)coc2cc(F)ccc12
InChIKey: OCBNOJQCXPPEOP-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human CYP17 expressed in Escherichia coli co-transfected with rat NADPH-P450 reductase using progesterone as substrate for 30 mins measured as formation of 17alpha-hydroxyprogesterone and 16alpha-hydroxyprogesterone in presence of NADPH
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 255.25, ALogP 2.92, HBA 3, HBD 0, PSA 43.1, QED 0.71
Compound (SMILES): O=c1cc(Cc2ccncc2)oc2cc(F)ccc12
InChIKey: BAYJSUFIUXAGBB-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human CYP17 expressed in Escherichia coli co-transfected with rat NADPH-P450 reductase using progesterone as substrate for 30 mins measured as formation of 17alpha-hydroxyprogesterone and 16alpha-hydroxyprogesterone in presence of NADPH
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 255.25, ALogP 2.92, HBA 3, HBD 0, PSA 43.1, QED 0.71
Compound (SMILES): COc1ccc2c(=O)c(Cc3c[nH]cn3)coc2c1
InChIKey: INEMNHDNMHFZNK-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human CYP17 expressed in Escherichia coli co-transfected with rat NADPH-P450 reductase using progesterone as substrate for 30 mins measured as formation of 17alpha-hydroxyprogesterone and 16alpha-hydroxyprogesterone in presence of NADPH
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 256.26, ALogP 2.12, HBA 4, HBD 1, PSA 68.12, QED 0.78
Compound (SMILES): O=c1c(Cc2c[nH]cn2)coc2cc(F)ccc12
InChIKey: RAMDGMPXIREKEE-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human CYP17 expressed in Escherichia coli co-transfected with rat NADPH-P450 reductase using progesterone as substrate for 30 mins measured as formation of 17alpha-hydroxyprogesterone and 16alpha-hydroxyprogesterone in presence of NADPH
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 244.22, ALogP 2.25, HBA 3, HBD 1, PSA 58.89, QED 0.75
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc(C(CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1ccc(CN2CCO[C@H](COc3ccccc3)C2)cc1F
InChIKey: XOWMGFHACPEJCJ-KRWDZBQOSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human D4 receptor expressed in HEK293 cell membrane by competitive inhibition based analysis
Measurement: IC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 331.39, ALogP 3.11, HBA 4, HBD 0, PSA 30.93, QED 0.81
Compound (SMILES): c1ccc(OC[C@@H]2CN(Cc3ccc4[nH]ccc4c3)CCO2)cc1
InChIKey: XHIUVRDSBNUEMG-IBGZPJMESA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 3.311 nM (pChEMBL 8.479999542236328)
Descriptors: MW 322.41, ALogP 3.45, HBA 3, HBD 1, PSA 37.49, QED 0.78
Compound (SMILES): Fc1ccc2c(CN3CCO[C@H](COc4cccc(Cl)n4)C3)c[nH]c2c1
InChIKey: FKVYTXSHXQFEOI-HNNXBMFYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D2L receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 375.83, ALogP 3.64, HBA 4, HBD 1, PSA 50.38, QED 0.69
Compound (SMILES): Clc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1
InChIKey: XINSSTGUTQPDTR-KRWDZBQOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D2L receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 333.88, ALogP 4.33, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): Cc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1C
InChIKey: PZYOBKWKADZRBF-IBGZPJMESA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D2L receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 327.49, ALogP 4.3, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): C=C1CC[C@]2(C(=O)O)CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@@H](OC(=O)/C=C/c6ccc(O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]2[C@H]1C
InChIKey: NXSZULOVDUOZKO-GYTPSKCOSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of PDE2A3 catalytic domain (222 to 904 residues) (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 616.84, ALogP 7.95, HBA 5, HBD 3, PSA 104.06, QED 0.18
Compound (SMILES): CN(C)CCOc1cccc(-c2ccc(Cl)cc2)c1CN1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(NCC4CCOCC4)c([N+](=O)[O-])c3)c(Oc3ccc4[nH]ccc4c3)c2)CC1
InChIKey: OEPSXIVYHBPSCA-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q64373
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The inhibition constant (Ki) is the dissociation constant of an enzyme-inhibitor complex or a protein/small molecule complex, wherein the small molecule is inhibiting binding of one protein to another protein or peptide. Where the Ki for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-XL) is greater than the limits of detection of the assay used. Where the binding selectivity ratio for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the selectivity of a particular compound for Bcl-2 over Bcl-XL is at least as great as the number indicated. Where the Ki for a compound is represented as < (less than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-2) is lower than the limit of detection of the assay used. Inhibition constants were determined using Wang's equation (Wang Z-X).
Measurement: Ki > 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 922.5, ALogP 8.41, HBA 12, HBD 3, PSA 171.61, QED 0.06
Compound (SMILES): Cc1c(-c2ccc(N3CCc4cccc(C(=O)Nc5nc6ccccc6s5)c4C3)nc2C(=O)O)cnn1CC12CC3CC(CC(C3)C1)C2
InChIKey: QCQQONWEDCOTBV-UHFFFAOYSA-N
Target: Bcl-2-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92843
Assay: Binding affinity to BCL-W (unknown origin) assessed as dissociation constant incubated for 1 hrs by TR-FRET assay
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 658.83, ALogP 7.59, HBA 8, HBD 2, PSA 113.24, QED 0.19
Compound (SMILES): O=C(Nc1ccc(CN2CCN(c3ccccc3)CC2)cc1)c1n[nH]c2ccccc12
InChIKey: QHWYQHKGOYXAON-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95819
Assay: Inhibition of human N-terminal GST-tagged HGK catalytic domain (1 to 328 residues) expressed in baculovirus expression system using fluorescence labelled moesin-derived peptide substrate by electrophoretic mobility shift assay
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 411.51, ALogP 4.14, HBA 4, HBD 2, PSA 64.26, QED 0.52
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccccc2)cc1
InChIKey: BOQIBRQHNFTPDW-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Binding affinity to human EP4 receptor by competitive binding assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.49, ALogP 3.21, HBA 4, HBD 1, PSA 70.08, QED 0.74
Compound (SMILES): Cn1c(C2CC2)nc2ccc(-n3ccc(OCc4ccc(Cl)s4)cc3=O)cc21
InChIKey: RPFBZAHRSRZYGF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp test
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.91, ALogP 4.9, HBA 6, HBD 0, PSA 49.05, QED 0.47
Compound (SMILES): O=C1OCc2cc(CCN3CCN(C(=O)Cc4ccc(-n5cnnn5)nc4)CC3)ccc21
InChIKey: DSTPQJIKZPOBFY-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Inhibition of rat ROMK expressed in HEK293 cells after 30 mins by [86Rb+] flux functional assay
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 433.47, ALogP 0.66, HBA 9, HBD 0, PSA 106.34, QED 0.52
Compound (SMILES): O=C1OCc2cc(CCC3CCN(C(=O)Cc4ccc(-n5cnnn5)nc4)CC3)ccc21
InChIKey: GEROKZRQGOYQDR-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35560
Assay: Inhibition of rat ROMK expressed in HEK293 cells after 30 mins by [86Rb+] flux functional assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 432.48, ALogP 2.14, HBA 8, HBD 0, PSA 103.1, QED 0.55
Compound (SMILES): Cc1cc(-n2cnnn2)cnc1CC(=O)N1CCN(CCc2ccc3c(c2C)COC3=O)CC1
InChIKey: RZUWLMYXOXGJLS-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology analysis
Measurement: IC50 = 52000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 461.53, ALogP 1.27, HBA 9, HBD 0, PSA 106.34, QED 0.51
Compound (SMILES): Cc1c(C(C)CN2CCN(C(=O)Cc3ccc(-n4cnnn4)nc3)CC2)ccc2c1COC2=O
InChIKey: JNXIDSMXBWTVGA-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology analysis
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 461.53, ALogP 1.53, HBA 9, HBD 0, PSA 106.34, QED 0.51
Compound (SMILES): Cc1c(C(F)CN2CCN(C(=O)Cc3ccc(-n4cnnn4)nc3)CC2)ccc2c1COC2=O
InChIKey: IWPLBAYOPYISRO-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology analysis
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 465.49, ALogP 1.43, HBA 9, HBD 0, PSA 106.34, QED 0.5
Compound (SMILES): NNc1nccc(C(=O)O)n1
InChIKey: AVMDBCMWSSIKTF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4E (SINGLE PROTEIN), Homo sapiens
UniProt: B2RXH2
Assay: Inhibition of KDM4E (unknown origin) using substrate peptide/ascorbate/2-OG/ Fe(2) as substrate preincubated for 15 mins followed by addition of substrate peptide/ ascorbate/2-OG/ Fe(2) measured after 1 hr by AlphaLISA method
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 154.13, ALogP -0.54, HBA 5, HBD 3, PSA 101.13, QED 0.39
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccc3c(c2)OCO3)cc1.Cl.O
InChIKey: GHJOTLLQCTXWNP-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Binding affinity to human EP3 receptor
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 440.5, ALogP 2.94, HBA 6, HBD 1, PSA 88.54, QED 0.68
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccn5)c4C(F)(F)F)n3)cc2)C1
InChIKey: UISONOSIQKJKKZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 471.4, ALogP 3.99, HBA 8, HBD 1, PSA 118.38, QED 0.45
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44
Compound (SMILES): O=C(CCCc1csc(/C=C/c2ccccc2)n1)NO
InChIKey: HJPIJALRLZVGMS-MDZDMXLPSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of human recombinant N-terminal His-tagged HDAC11 (1 to 347 residues) expressed in insect cells/baculovirus expression system using RHK-K(Ac)-AMC as substrate by fluorescence assay
Measurement: IC50 = 32820 nM (pChEMBL 4.480000019073486)
Descriptors: MW 288.37, ALogP 3.14, HBA 4, HBD 2, PSA 62.22, QED 0.63
Compound (SMILES): COc1ccc(CN2CCO[C@H](COc3ccccc3)C2)cc1F
InChIKey: XOWMGFHACPEJCJ-KRWDZBQOSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 331.39, ALogP 3.11, HBA 4, HBD 0, PSA 30.93, QED 0.81
Compound (SMILES): c1ccc(OC[C@@H]2CN(Cc3ccc4[nH]ccc4c3)CCO2)cc1
InChIKey: XHIUVRDSBNUEMG-IBGZPJMESA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D4 receptor expressed in CHOK1 cells
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 322.41, ALogP 3.45, HBA 3, HBD 1, PSA 37.49, QED 0.78
Compound (SMILES): Fc1ccc2c(CN3CCO[C@H](COc4cccc(Cl)n4)C3)c[nH]c2c1
InChIKey: FKVYTXSHXQFEOI-HNNXBMFYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D2S receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 375.83, ALogP 3.64, HBA 4, HBD 1, PSA 50.38, QED 0.69
Compound (SMILES): Clc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1
InChIKey: XINSSTGUTQPDTR-KRWDZBQOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D2S receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 333.88, ALogP 4.33, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): Cc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1C
InChIKey: PZYOBKWKADZRBF-IBGZPJMESA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D2S receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 327.49, ALogP 4.3, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): C=C1CC[C@]2(C(=O)O)CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@@H](OC(=O)/C=C/c6ccc(O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]2[C@H]1C
InChIKey: NXSZULOVDUOZKO-GYTPSKCOSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q01064
Assay: Inhibition of PDE1B2 catalytic domain (10 to 487 residues) (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 = 2629 nM (pChEMBL 5.579999923706055)
Descriptors: MW 616.84, ALogP 7.95, HBA 5, HBD 3, PSA 104.06, QED 0.18
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccccc2)cc1
InChIKey: BOQIBRQHNFTPDW-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Binding affinity to human EP3 receptor by competitive binding assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.49, ALogP 3.21, HBA 4, HBD 1, PSA 70.08, QED 0.74
Compound (SMILES): NNc1nccc(C(=O)O)n1
InChIKey: AVMDBCMWSSIKTF-UHFFFAOYSA-N
Target: Probable JmjC domain-containing histone demethylation protein 2C (SINGLE PROTEIN), Homo sapiens
UniProt: Q15652
Assay: Inhibition of KDM3C (unknown origin) using substrate peptide/ascorbate/2-OG/ Fe(2) as substrate preincubated for 15 mins followed by addition of substrate peptide/ ascorbate/2-OG/ Fe(2) measured after 1 hr by AlphaLISA method
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 154.13, ALogP -0.54, HBA 5, HBD 3, PSA 101.13, QED 0.39
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccc3c(c2)OCO3)cc1.Cl.O
InChIKey: GHJOTLLQCTXWNP-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Binding affinity to human EP2 receptor
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 440.5, ALogP 2.94, HBA 6, HBD 1, PSA 88.54, QED 0.68
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccn5)c4C(F)(F)F)n3)cc2)C1
InChIKey: UISONOSIQKJKKZ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 471.4, ALogP 3.99, HBA 8, HBD 1, PSA 118.38, QED 0.45
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44
Compound (SMILES): O=C(CCCc1csc(/C=C/c2ccccc2)n1)NO
InChIKey: HJPIJALRLZVGMS-MDZDMXLPSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant C-terminal His-tagged HDAC8 (1 to 377 residues) expressed in insect cells using RHK-K(Ac)-K(Ac)-AMC as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 1536 nM (pChEMBL 5.809999942779541)
Descriptors: MW 288.37, ALogP 3.14, HBA 4, HBD 2, PSA 62.22, QED 0.63
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc(C(CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1ccc(CN2CCO[C@H](COc3ccccc3)C2)cc1F
InChIKey: XOWMGFHACPEJCJ-KRWDZBQOSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 331.39, ALogP 3.11, HBA 4, HBD 0, PSA 30.93, QED 0.81
Compound (SMILES): c1ccc(OC[C@@H]2CN(Cc3ccc4[nH]ccc4c3)CCO2)cc1
InChIKey: XHIUVRDSBNUEMG-IBGZPJMESA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D4 receptor expressed in CHOK1 cells
Measurement: Ki = 15.9 nM (pChEMBL 7.800000190734863)
Descriptors: MW 322.41, ALogP 3.45, HBA 3, HBD 1, PSA 37.49, QED 0.78
Compound (SMILES): Fc1ccc2c(CN3CCO[C@H](COc4cccc(Cl)n4)C3)c[nH]c2c1
InChIKey: FKVYTXSHXQFEOI-HNNXBMFYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D3 receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 375.83, ALogP 3.64, HBA 4, HBD 1, PSA 50.38, QED 0.69
Compound (SMILES): Clc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1
InChIKey: XINSSTGUTQPDTR-KRWDZBQOSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D3 receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 333.88, ALogP 4.33, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): Cc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1C
InChIKey: PZYOBKWKADZRBF-IBGZPJMESA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-Spiperone from human recombinant dopamine D3 receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 327.49, ALogP 4.3, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): C=C1CC[C@]2(C(=O)O)CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@@H](OC(=O)/C=C/c6ccc(O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]2[C@H]1C
InChIKey: NXSZULOVDUOZKO-GYTPSKCOSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of PDE4D2 catalytic domain (86 to 413 residues) (unknown origin) using [3H]-cAMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 616.84, ALogP 7.95, HBA 5, HBD 3, PSA 104.06, QED 0.18
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccccc2)cc1
InChIKey: BOQIBRQHNFTPDW-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Binding affinity to human EP2 receptor by competitive binding assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.49, ALogP 3.21, HBA 4, HBD 1, PSA 70.08, QED 0.74
Compound (SMILES): NNc1nccc(C(=O)O)n1
InChIKey: AVMDBCMWSSIKTF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (unknown origin) using substrate peptide/ascorbate/2-OG/ Fe(2) as substrate preincubated for 15 mins followed by addition of substrate peptide/ ascorbate/2-OG/ Fe(2) measured after 1 hr by AlphaLISA method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 154.13, ALogP -0.54, HBA 5, HBD 3, PSA 101.13, QED 0.39
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccc3c(c2)OCO3)cc1.Cl.O
InChIKey: GHJOTLLQCTXWNP-UHFFFAOYSA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43119
Assay: Binding affinity to human IP receptor
Measurement: Ki = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 440.5, ALogP 2.94, HBA 6, HBD 1, PSA 88.54, QED 0.68
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccn5)c4C(F)(F)F)n3)cc2)C1
InChIKey: UISONOSIQKJKKZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 471.4, ALogP 3.99, HBA 8, HBD 1, PSA 118.38, QED 0.45
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44
Compound (SMILES): O=C(CCCc1csc(/C=C/c2ccccc2)n1)NO
InChIKey: HJPIJALRLZVGMS-MDZDMXLPSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human recombinant N-terminal GST-tagged HDAC6 (1 to 1215 residues) expressed in sf9 cells using RHK-K(Ac)-AMC as substrate incubated for 90 mins by fluorescence assay
Measurement: IC50 = 567.4 nM (pChEMBL 6.25)
Descriptors: MW 288.37, ALogP 3.14, HBA 4, HBD 2, PSA 62.22, QED 0.63
Compound (SMILES): COc1ccc(CN2CCO[C@H](COc3ccccc3)C2)cc1F
InChIKey: XOWMGFHACPEJCJ-KRWDZBQOSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 331.39, ALogP 3.11, HBA 4, HBD 0, PSA 30.93, QED 0.81
Compound (SMILES): Fc1ccc2c(CN3CCO[C@H](COc4cccc(Cl)n4)C3)c[nH]c2c1
InChIKey: FKVYTXSHXQFEOI-HNNXBMFYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH-23390 from human recombinant dopamine D5 receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 375.83, ALogP 3.64, HBA 4, HBD 1, PSA 50.38, QED 0.69
Compound (SMILES): Clc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1
InChIKey: XINSSTGUTQPDTR-KRWDZBQOSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH-23390 from human recombinant dopamine D5 receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 333.88, ALogP 4.33, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): Cc1ccc(CN2CCO[C@H](CSc3ccccc3)C2)cc1C
InChIKey: PZYOBKWKADZRBF-IBGZPJMESA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH-23390 from human recombinant dopamine D5 receptor expressed in CHO cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 327.49, ALogP 4.3, HBA 3, HBD 0, PSA 12.47, QED 0.76
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccccc2)cc1
InChIKey: BOQIBRQHNFTPDW-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP1 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P34995
Assay: Binding affinity to human EP1 receptor by competitive binding assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 396.49, ALogP 3.21, HBA 4, HBD 1, PSA 70.08, QED 0.74
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccn5)c4C(F)(F)F)n3)cc2)C1
InChIKey: UISONOSIQKJKKZ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at human S1P3 receptor expressed in EDG3-Ga15-bla HEK293T cell membranes assessed as stimulation of [35S]GTPgamma binding incubated for 45 mins by liquid scintillation counting method
Measurement: EC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 471.4, ALogP 3.99, HBA 8, HBD 1, PSA 118.38, QED 0.45
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44
Compound (SMILES): O=C(CCCc1csc(/C=C/c2ccccc2)n1)NO
InChIKey: HJPIJALRLZVGMS-MDZDMXLPSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of human recombinant C-terminal His-tagged HDAC5 (657 to 1123 residues) expressed in insect cells using Boc-K(TFA)-AMC as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 26570 nM (pChEMBL 4.579999923706055)
Descriptors: MW 288.37, ALogP 3.14, HBA 4, HBD 2, PSA 62.22, QED 0.63
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc(C(CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1ccc(CN2CCO[C@H](COc3ccccc3)C2)cc1F
InChIKey: XOWMGFHACPEJCJ-KRWDZBQOSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 331.39, ALogP 3.11, HBA 4, HBD 0, PSA 30.93, QED 0.81
Compound (SMILES): Cc1ccc(N(CCN2CCC(OCC(=O)O)CC2)C(=O)c2ccccc2)cc1
InChIKey: BOQIBRQHNFTPDW-UHFFFAOYSA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43119
Assay: Binding affinity to human IP receptor by competitive binding assay
Measurement: Ki = 990 nM (pChEMBL 6)
Descriptors: MW 396.49, ALogP 3.21, HBA 4, HBD 1, PSA 70.08, QED 0.74
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccn5)c4C(F)(F)F)n3)cc2)C1
InChIKey: UISONOSIQKJKKZ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at human S1P1 receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgamma binding incubated for 45 mins by liquid scintillation counting method
Measurement: EC50 = 0.71 nM (pChEMBL 9.149999618530273)
Descriptors: MW 471.4, ALogP 3.99, HBA 8, HBD 1, PSA 118.38, QED 0.45
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44
Compound (SMILES): O=C(CCCc1csc(/C=C/c2ccccc2)n1)NO
InChIKey: HJPIJALRLZVGMS-MDZDMXLPSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human recombinant N-terminal GST-tagged C-terminal His-tagged HDAC4 (627 to 1084 residues) expressed in insect cells using Boc-K(TFA)-AMC as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 19730 nM (pChEMBL 4.710000038146973)
Descriptors: MW 288.37, ALogP 3.14, HBA 4, HBD 2, PSA 62.22, QED 0.63
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44
Compound (SMILES): O=C(CCCc1csc(/C=C/c2ccccc2)n1)NO
InChIKey: HJPIJALRLZVGMS-MDZDMXLPSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant C-terminal GST-tagged HDAC2 (1 to 488 residues) expressed in insect cells using RHK-K(Ac)-AMC as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 288.37, ALogP 3.14, HBA 4, HBD 2, PSA 62.22, QED 0.63
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
InChIKey: RRPYZEWVBYBTJC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.41, ALogP 4.59, HBA 7, HBD 1, PSA 105.49, QED 0.44