lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCC(=O)c1c(O)ccc2ccc(=O)oc12
InChIKey: DVLIOVBNBOBBGS-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 218.21, ALogP 2.09, HBA 4, HBD 1, PSA 67.51, QED 0.62
Compound (SMILES): COc1cc2oc(=O)ccc2cc1C(C)=O
InChIKey: QDWMZGNQFSIPKO-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 218.21, ALogP 2, HBA 4, HBD 0, PSA 56.51, QED 0.57
Compound (SMILES): CCOc1cc2oc(=O)ccc2cc1C(C)=O
InChIKey: YPWNHEXIUIFWSP-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of full length human CA2 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 232.24, ALogP 2.39, HBA 4, HBD 0, PSA 56.51, QED 0.6
Compound (SMILES): CCCOc1cc2oc(=O)ccc2cc1C(C)=O
InChIKey: VIKCPCBUFQJHPC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of full length human CA2 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 246.26, ALogP 2.78, HBA 4, HBD 0, PSA 56.51, QED 0.61
Compound (SMILES): Cc1cc(Cl)cc2c1OC(C(F)(F)F)C(C(=O)O)=C2
InChIKey: NONBXOPYDWLZGR-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 pre-incubated for 15 mins before fluorometric substrate addition by fluorescence based assay
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 292.64, ALogP 3.44, HBA 2, HBD 1, PSA 46.53, QED 0.86
Compound (SMILES): Cc1cc(Cl)c2c(c1)C=C(C(=O)O)C(C(F)(F)F)O2
InChIKey: DIUCLSCBUOAEQY-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human recombinant COX1 pre-incubated for 15 mins before fluorometric substrate addition by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 292.64, ALogP 3.44, HBA 2, HBD 1, PSA 46.53, QED 0.86
Compound (SMILES): COc1ccc2cc(-c3n[nH]c4cccnc34)[nH]c2c1
InChIKey: PRASIGARSOSUQT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of ABL1
Measurement: IC50 = 7680 nM (pChEMBL 5.119999885559082)
Descriptors: MW 264.29, ALogP 3.11, HBA 3, HBD 2, PSA 66.59, QED 0.58
Compound (SMILES): CCCCOc1cc2oc(=O)ccc2cc1C(C)=O
InChIKey: DHDLGZWXFVLJCQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant CA9 catalytic domain by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 260.29, ALogP 3.17, HBA 4, HBD 0, PSA 56.51, QED 0.47
Compound (SMILES): COc1ccc2ccc(=O)oc2c1C(C)=O
InChIKey: OTYBDEHZHXKGBO-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 218.21, ALogP 2, HBA 4, HBD 0, PSA 56.51, QED 0.57
Compound (SMILES): CCOc1ccc2ccc(=O)oc2c1C(C)=O
InChIKey: KWMPAFCHEJYQEQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 232.24, ALogP 2.39, HBA 4, HBD 0, PSA 56.51, QED 0.6
Compound (SMILES): CCCOc1ccc2ccc(=O)oc2c1C(C)=O
InChIKey: XDGJEUMPGBUXDY-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 246.26, ALogP 2.78, HBA 4, HBD 0, PSA 56.51, QED 0.61
Compound (SMILES): CCCCOc1ccc2ccc(=O)oc2c1C(C)=O
InChIKey: ULYJCIVHEFSJIF-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 260.29, ALogP 3.17, HBA 4, HBD 0, PSA 56.51, QED 0.47
Compound (SMILES): CCC(=O)c1c(OC)ccc2ccc(=O)oc12
InChIKey: XQJPTVQKFUWDCL-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 232.24, ALogP 2.39, HBA 4, HBD 0, PSA 56.51, QED 0.6
Compound (SMILES): CCOc1ccc2ccc(=O)oc2c1C(=O)CC
InChIKey: LJTVZULEIDSNAK-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 246.26, ALogP 2.78, HBA 4, HBD 0, PSA 56.51, QED 0.61
Compound (SMILES): CCCOc1ccc2ccc(=O)oc2c1C(=O)CC
InChIKey: CVYSNMWNCSOWAN-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of full length human CA1 cytosolic isoform by stopped-flow CO2 hydration method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 260.29, ALogP 3.17, HBA 4, HBD 0, PSA 56.51, QED 0.61
Compound (SMILES): NCCc1c[nH]c2ccc(OCc3ccccc3)cc12
InChIKey: WKPDXBXNJWWWGQ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 receptor expressed in human T-REx-293 cells assessed as inhibition of icilin-induced 45calcium influx treated 5 mins before icilin challenge measured after 5 mins
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 266.34, ALogP 3.25, HBA 2, HBD 2, PSA 51.04, QED 0.74
Compound (SMILES): O=C(O)CCC(=O)/C=C/c1ccc2ccccc2c1
InChIKey: QWXZWGIRNZRBGH-SOFGYWHQSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55940 from human recombinant CB2 receptor expressed in HEK293 cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 254.28, ALogP 3.29, HBA 2, HBD 1, PSA 54.37, QED 0.83
Compound (SMILES): O=C(O)CCCC(=O)/C=C/c1ccc2ccccc2c1
InChIKey: NKWVJBIWWHOTRE-PKNBQFBNSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55940 from human recombinant CB2 receptor expressed in HEK293 cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 268.31, ALogP 3.68, HBA 2, HBD 1, PSA 54.37, QED 0.81
Compound (SMILES): NCCc1c[nH]c2ccc(Cl)cc12
InChIKey: FVQKQPVVCKOWLM-UHFFFAOYSA-N
Target: Norepinephrine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9WTR4
Assay: Induction of NET-mediated norepinephrine release in rat brain synaptosomes by [3H]NE release assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 194.66, ALogP 2.32, HBA 1, HBD 2, PSA 41.81, QED 0.76
Compound (SMILES): NCCc1c[nH]c2ccc(Br)cc12
InChIKey: CGHUQJRRADEHTQ-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Induction of DAT-mediated dopamine release in rat brain synaptosomes by [3H]DA release assay
Measurement: EC50 = 478 nM (pChEMBL 6.320000171661377)
Descriptors: MW 239.12, ALogP 2.43, HBA 1, HBD 2, PSA 41.81, QED 0.83
Compound (SMILES): O=C(c1ccccc1)n1nnc2ccccc21
InChIKey: UJEMOXPSTTXLRE-UHFFFAOYSA-N
Target: 4'-phosphopantetheinyl transferase ffp (SINGLE PROTEIN), Bacillus subtilis
UniProt: Q9F4F7
Assay: PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase). (Class of assay: confirmatory) 
Measurement: Potency = 39810.7 nM (pChEMBL 4.400000095367432)
Descriptors: MW 223.24, ALogP 2.12, HBA 4, HBD 0, PSA 47.78, QED 0.63
Compound (SMILES): CCN1CCN(c2ccc(O)c(-c3ccc(C#C[C@]4(CN5Cc6ccc(OC)cc6C5=O)NC(=O)NC4=O)cc3F)n2)CC1
InChIKey: NSKDLLYTWJVRPJ-JGCGQSQUSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of TACE
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 598.64, ALogP 2.33, HBA 8, HBD 3, PSA 127.34, QED 0.29
Compound (SMILES): Cc1cc2c(c(C)c1Cl)C=C(C(=O)O)C(C(F)(F)F)O2
InChIKey: UNEVTVWOSGJGLU-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human recombinant COX1 pre-incubated for 15 mins before fluorometric substrate addition by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 306.67, ALogP 3.75, HBA 2, HBD 1, PSA 46.53, QED 0.86
Compound (SMILES): CCC(=O)Nc1nnc(S(N)(=O)=O)s1
InChIKey: PCBBBQKRWNGNDW-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 expressed in Escherichia coli BL21 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 236.28, ALogP -0.47, HBA 6, HBD 2, PSA 115.04, QED 0.69
Compound (SMILES): CCCC(=O)Nc1nnc(S(N)(=O)=O)s1
InChIKey: HZIYHIRJHYIRQO-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 expressed in Escherichia coli BL21 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 250.31, ALogP -0.08, HBA 6, HBD 2, PSA 115.04, QED 0.73
Compound (SMILES): CC(C)C(=O)Nc1nnc(S(N)(=O)=O)s1
InChIKey: DVZGQBMHOJKRPI-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 expressed in Escherichia coli BL21 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 0.44 nM (pChEMBL 9.359999656677246)
Descriptors: MW 250.31, ALogP -0.22, HBA 6, HBD 2, PSA 115.04, QED 0.72
Compound (SMILES): OC[C@@H](O)CN1CCN(c2ccccc2)CC1
InChIKey: PTVWPYVOOKLBCG-ZDUSSCGKSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Compound was evaluated for inhibition of human PDE4D in an in vitro cell free assay measured by scintillation proximity assay
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 236.31, ALogP 0.16, HBA 4, HBD 2, PSA 46.94, QED 0.78
Compound (SMILES): COC(=O)c1sccc1NC(=O)Cc1cccs1
InChIKey: CXOCENPNQSXLGZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of recombinant p38alpha after 60 mins by TR-FRET assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 281.36, ALogP 2.78, HBA 5, HBD 1, PSA 55.4, QED 0.88
Compound (SMILES): COC(=O)c1sccc1NC(=O)Cc1ccccc1
InChIKey: YJXMVZWBSKFEBU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of recombinant JNK3 after 60 mins by TR-FRET assay
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 275.33, ALogP 2.72, HBA 4, HBD 1, PSA 55.4, QED 0.87
Compound (SMILES): COC(=O)c1sccc1NC(=O)Cc1ccncc1
InChIKey: UDSAZFJLDCDUQO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of recombinant JNK3 after 60 mins by TR-FRET assay
Measurement: IC50 = 17200 nM (pChEMBL 4.760000228881836)
Descriptors: MW 276.32, ALogP 2.11, HBA 5, HBD 1, PSA 68.29, QED 0.87
Compound (SMILES): CC(=O)c1sccc1NC(=O)Cc1ccccc1
InChIKey: GRNZWZUKBPDEBP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of recombinant JNK3 after 60 mins by TR-FRET assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 259.33, ALogP 3.13, HBA 3, HBD 1, PSA 46.17, QED 0.86
Compound (SMILES): CC(=O)Oc1c2occc2cc2ccc(=O)oc12
InChIKey: LPTRRECWRHWOEU-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: PUBCHEM_BIOASSAY: Counterscreen qHTS for Inhibitors of Tau Fibril Formation, Fluorescence Polarization. This assay monitors tau fibrillation by fluorescence polarization (FP) of Alexa 594-labeled K18 P301L, which does not fibrillize readily but incorporates into growing filaments of unlabeled tau. (Class of assay: confirmatory) [Related pubchem assays: 596 ]
Measurement: Potency = 35481.3 nM (pChEMBL 4.449999809265137)
Descriptors: MW 244.2, ALogP 2.46, HBA 5, HBD 0, PSA 69.65, QED 0.37
Compound (SMILES): CCOC(=O)c1sccc1NC(=O)Cc1ccccc1
InChIKey: RJDMNHJOMJVPHJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of recombinant JNK3 after 60 mins by TR-FRET assay
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 289.36, ALogP 3.11, HBA 4, HBD 1, PSA 55.4, QED 0.86
Compound (SMILES): O=C(/C=C/c1ccc(Cl)cc1)c1ccc2c(c1)OCO2
InChIKey: XCQPLWRKVKRYTP-XVNBXDOJSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human MAO-A
Measurement: IC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 286.71, ALogP 3.96, HBA 3, HBD 0, PSA 35.53, QED 0.63
Compound (SMILES): NC(=O)c1sccc1NC(=O)Cc1ccccc1
InChIKey: INZMHUJPOZBGRG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of recombinant JNK3 after 60 mins by TR-FRET assay
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 260.32, ALogP 2.03, HBA 3, HBD 2, PSA 72.19, QED 0.88
Compound (SMILES): FC(F)(F)c1ccc(Nc2ncnc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: HSXSQLHUTDJCHN-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Functional Assay: HEK293 cells were transfected with human TRPV1 cloned in pcDNA3.1zeo(+) using the Effectene non-liposomal lipid based transfection kit (Qiagen) (hTRPV1/HEK293). hTRPV1/HEK293 cells were routinely grown as monolayers under selection in zeocin (200 μg/mL; Invitrogen) in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, and penicillin/streptomycin (50 units/mL) in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 453.39, ALogP 5.26, HBA 5, HBD 1, PSA 53.94, QED 0.55
Compound (SMILES): Cc1nc2c(c(Nc3ccc(C(F)(F)F)cc3)n1)CCN(c1ncccc1C(F)(F)F)CC2
InChIKey: MVHMAEGHMUCPTK-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 467.42, ALogP 5.57, HBA 5, HBD 1, PSA 53.94, QED 0.51
Compound (SMILES): CC(C)(O)c1ccc(Nc2nc(N3CCOCC3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: XFHVQJIZVSRSCY-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human recombinant TRPV1 assessed as inhibition of capsaicin-induced in intracellular calcium levels by cell-based FLIPR assay
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 528.58, ALogP 4.3, HBA 8, HBD 2, PSA 86.64, QED 0.51
Compound (SMILES): Cc1ccc2c(N3CCN(CCc4c(C)ccc5[nH]c(=O)ccc45)CC3)cccc2n1
InChIKey: WJEBTWQLGLLSGW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide in human hERG expressed in CHO cells by proximity assay
Measurement: Ki = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 412.54, ALogP 4.06, HBA 4, HBD 1, PSA 52.23, QED 0.55
Compound (SMILES): Cc1ccc2c(N3CCN(CCc4c(C)ccc5c4ccc(=O)n5C)CC3)cccc2n1
InChIKey: ZJRBDUXTOJWXLZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide in human hERG expressed in CHO cells by proximity assay
Measurement: Ki = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 426.56, ALogP 4.07, HBA 5, HBD 0, PSA 41.37, QED 0.49
Compound (SMILES): O=c1cc(OCc2ccccc2)ccn1-c1ccc2c(cnn2CC2=NCCN2)c1
InChIKey: VAXDISKYVOZCHP-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 399.45, ALogP 2.77, HBA 7, HBD 1, PSA 73.44, QED 0.54
Compound (SMILES): CN1CCC(C(=O)OCc2ccccc2)(c2ccc(Cl)c(Cl)c2)CC1.Cl
InChIKey: JQCIVYLOBXKYHU-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Displacement of [3H]nisoxetine from norepinephrine transporter in Sprague-Dawley rat frontal cortex after 1 hr by liquid scintillation counting
Measurement: Ki = 901 nM (pChEMBL 6.039999961853027)
Descriptors: MW 378.3, ALogP 4.7, HBA 3, HBD 0, PSA 29.54, QED 0.72
Compound (SMILES): COc1ccc(COC(=O)C2(c3ccc(Cl)c(Cl)c3)CCN(C)CC2)cc1.Cl
InChIKey: IEEMLIPWTIGUNK-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Displacement of [3H]nisoxetine from norepinephrine transporter in Sprague-Dawley rat frontal cortex after 1 hr by liquid scintillation counting
Measurement: Ki = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 408.33, ALogP 4.71, HBA 4, HBD 0, PSA 38.77, QED 0.67
Compound (SMILES): CCO[C@H]1CN([C@H]2CC[C@@](O)(c3ccccc3)CC2)C[C@@H]1NC(=O)CNC(=O)c1cccc(C(F)(F)F)c1
InChIKey: KLHQJQIPLYZOOT-TTZMFTMZSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at human CCR2 assessed as inhibition of MCP1 induced chemotaxis after 30 mins
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 533.59, ALogP 3.47, HBA 5, HBD 3, PSA 90.9, QED 0.48
Compound (SMILES): CCC(O)(c1cn(Cc2ccc3c(-c4ccccc4)c(CO)sc3c2)nn1)C(F)(F)F
InChIKey: VHUHEHFTHOOWND-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of labeled MK-499 from human ERG
Measurement: Ki = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 447.48, ALogP 4.86, HBA 6, HBD 2, PSA 71.17, QED 0.44
Compound (SMILES): CCC(O)(c1cn(Cc2ccc3c(-c4ccccc4)c(C(C)(C)O)sc3c2)nn1)C(F)(F)F
InChIKey: FUWQAKNTNMMDBM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of labeled MK-499 from human ERG
Measurement: Ki = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 475.54, ALogP 5.6, HBA 6, HBD 2, PSA 71.17, QED 0.38
Compound (SMILES): CC(C)[C@@H](Nc1nc2cc[nH]c(=O)c2c2cc(F)ccc12)C(F)(F)F
InChIKey: SDYVZQPJOBQDEW-CQSZACIVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding affinity to human ERG expressed in HEK cells by radioligand displacement assay
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 353.32, ALogP 4.21, HBA 3, HBD 2, PSA 57.78, QED 0.55
Compound (SMILES): Cn1c(=O)c(-c2ccc(F)cc2F)c(CCc2ccccc2)c2cc(OCC(=O)NCc3ccccc3)ccc21
InChIKey: PVJNHUBIFGYWIU-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor transfected in CHO cells assessed as inhibition of NECA-induced cAMP accumulation treated 15 mins before NECA challenge measured after 1 hr
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 538.59, ALogP 5.96, HBA 4, HBD 1, PSA 60.33, QED 0.25
Compound (SMILES): COc1ccc2[nH]c(=O)c(S(C)(=O)=O)c(CCc3ccccc3)c2c1
InChIKey: BXUGBCMKSUJJPL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor transfected in CHO cells assessed as inhibition of NECA-induced cAMP accumulation treated 15 mins before NECA challenge measured after 1 hr
Measurement: Ki = 3474 nM (pChEMBL 5.460000038146973)
Descriptors: MW 357.43, ALogP 2.73, HBA 4, HBD 1, PSA 76.23, QED 0.76
Compound (SMILES): CN1c2ccccc2C(NCCCCCCC(=O)O)c2ccc(Cl)cc2S1(=O)=O
InChIKey: JICJBGPOMZQUBB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Compound was evaluated for inhibition of human KCNH2 in an in vitro assay with cellular components measured by membrane filtration, radioactivity method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 436.96, ALogP 4.19, HBA 4, HBD 2, PSA 86.71, QED 0.61
Compound (SMILES): COc1ccc2[nH]c(SCC(=O)Nc3ccccc3OC)nc2c1
InChIKey: XXLGDHYIVLLMTF-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues) /human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells using histone H4 as substrate preincubated for 15 mins followed by substrate/S-adenosyl methionine addition measured after 60 mins by alpha LISA assay
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 343.41, ALogP 3.31, HBA 5, HBD 2, PSA 76.24, QED 0.67
Compound (SMILES): FC(F)(F)c1ccc(Nc2nc(C3CC3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: OVZUUNWOMYLSBF-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Functional Assay: HEK293 cells were transfected with human TRPV1 cloned in pcDNA3.1zeo(+) using the Effectene non-liposomal lipid based transfection kit (Qiagen) (hTRPV1/HEK293). hTRPV1/HEK293 cells were routinely grown as monolayers under selection in zeocin (200 μg/mL; Invitrogen) in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, and penicillin/streptomycin (50 units/mL) in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 493.46, ALogP 6.14, HBA 5, HBD 1, PSA 53.94, QED 0.44
Compound (SMILES): CC(C)c1nc2c(c(Nc3ccc(C(F)(F)F)cc3)n1)CCN(c1ncccc1C(F)(F)F)CC2
InChIKey: HXNNMGDMBHIQNA-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 495.47, ALogP 6.38, HBA 5, HBD 1, PSA 53.94, QED 0.43
Compound (SMILES): CC(C)(C#N)c1ccc(Nc2nc(N3CCCCC3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: LNVDMVMPFFDPMA-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 535.62, ALogP 6.03, HBA 7, HBD 1, PSA 80.97, QED 0.43
Compound (SMILES): Cc1ccc2c(N3CCN(CCc4c(F)ccc5c4ccc(=O)n5C)CC3)cccc2n1
InChIKey: ATIOXJJZTVLJHG-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide in human hERG expressed in CHO cells by proximity assay
Measurement: Ki = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 430.53, ALogP 3.9, HBA 5, HBD 0, PSA 41.37, QED 0.49
Compound (SMILES): Cc1ccc2c(N3CCN(CCc4c(Cl)ccc5c4ccc(=O)n5C)CC3)cccc2n1
InChIKey: YSWZYQKMDBCHKA-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide in human hERG expressed in CHO cells by proximity assay
Measurement: Ki = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 446.98, ALogP 4.41, HBA 5, HBD 0, PSA 41.37, QED 0.47
Compound (SMILES): CN1CCC(C(=O)OCc2ccc([N+](=O)[O-])cc2)(c2ccc(Cl)c(Cl)c2)CC1.Cl
InChIKey: XOWUJOWPZFHFSA-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Displacement of [3H]nisoxetine from norepinephrine transporter in Sprague-Dawley rat frontal cortex after 1 hr by liquid scintillation counting
Measurement: Ki = 333 nM (pChEMBL 6.480000019073486)
Descriptors: MW 423.3, ALogP 4.61, HBA 5, HBD 0, PSA 72.68, QED 0.4
Compound (SMILES): CCO[C@H]1CN([C@H]2CC[C@@](O)(c3ccc(C)cc3)CC2)C[C@@H]1NC(=O)CNC(=O)c1cccc(C(F)(F)F)c1
InChIKey: JQPQRYDIQFLFAA-MGDCHWCSSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at human CCR2 assessed as inhibition of MCP1 induced chemotaxis after 30 mins
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 547.62, ALogP 3.78, HBA 5, HBD 3, PSA 90.9, QED 0.47
Compound (SMILES): CCC(O)(c1cn(Cc2ccc3c(-c4ccccc4)c(C(C)O)sc3c2)nn1)C(F)(F)F
InChIKey: OGKPZQUWFNSSNB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of labeled MK-499 from human ERG
Measurement: Ki = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 461.51, ALogP 5.42, HBA 6, HBD 2, PSA 71.17, QED 0.4
Compound (SMILES): CCC(O)(c1cn(Cc2ccc3c(-c4ccccc4)c(C(C)=O)sc3c2)nn1)C(F)(F)F
InChIKey: QCVHQBKSBJJNID-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of labeled MK-499 from human ERG
Measurement: Ki = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 459.49, ALogP 5.57, HBA 6, HBD 1, PSA 68.01, QED 0.38
Compound (SMILES): CC(C)[C@@H](Nc1nc2cc[nH]c(=O)c2c2cnccc12)C(F)(F)F
InChIKey: DBPPYNQBKGUMSZ-CYBMUJFWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding affinity to human ERG expressed in HEK cells by radioligand displacement assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 336.32, ALogP 3.47, HBA 4, HBD 2, PSA 70.67, QED 0.72
Compound (SMILES): CS(=O)(=O)c1c(CCc2ccccc2)c2cc(OCC(=O)Nc3ccccc3)ccc2[nH]c1=O
InChIKey: XZSDQSOTBNONQM-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor transfected in CHO cells assessed as inhibition of NECA-induced cAMP accumulation treated 15 mins before NECA challenge measured after 1 hr
Measurement: Ki = 1675 nM (pChEMBL 5.78000020980835)
Descriptors: MW 476.55, ALogP 3.73, HBA 5, HBD 2, PSA 105.33, QED 0.4
Compound (SMILES): CS(=O)(=O)c1c(CCc2ccccc2)c2cc(OCC(=O)NCC3CC3)ccc2[nH]c1=O
InChIKey: KTHZNTXIIWQWBY-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from human adenosine A1 receptor expressed in CHO-K1 cells after 2 hrs
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 454.55, ALogP 2.62, HBA 5, HBD 2, PSA 105.33, QED 0.52
Compound (SMILES): COc1ccc(CCNC(=O)Nc2ccc(Cl)cc2)cc1
InChIKey: OVFMMJNKICPJJH-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Allosteric antagonist activity at human CB1 receptor expressed in CHO-RD-HGA16 cells overexpressing Galpha16 assessed as inhibition of CP55940-stimulated calcium mobilization incubated for 15 mins FLIPR assay
Measurement: IC50 = 213.8 nM (pChEMBL 6.670000076293945)
Descriptors: MW 304.78, ALogP 3.71, HBA 2, HBD 2, PSA 50.36, QED 0.88
Compound (SMILES): FC(F)(F)c1ccc(Nc2nc(-c3ccccc3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: FPKQFKIPZGTPNB-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human recombinant TRPV1 assessed as inhibition of capsaicin-induced in intracellular calcium levels by cell-based FLIPR assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 529.49, ALogP 6.93, HBA 5, HBD 1, PSA 53.94, QED 0.29
Compound (SMILES): Nc1nc2c(c(Nc3ccc(C(F)(F)F)cc3)n1)CCN(c1ncccc1C(F)(F)F)CC2
InChIKey: CFXQZUHPSHEGED-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human recombinant TRPV1 assessed as inhibition of capsaicin-induced in intracellular calcium levels by cell-based FLIPR assay
Measurement: IC50 = 1058 nM (pChEMBL 5.980000019073486)
Descriptors: MW 468.41, ALogP 4.84, HBA 6, HBD 2, PSA 79.96, QED 0.54
Compound (SMILES): CC(C)(C#N)c1ccc(Nc2nc(N3CCOCC3)nc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
InChIKey: OEFUXFGUSUQBHB-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Functional Assay: The assay was performed as described below, using HEK293 cells transfected with rat TRPV1 (rTRPV1/HEK293). These cells had a geneticin selection marker and were grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL) supplemented with 10% fetal bovine serum, penicillin/streptomycin (50 units/mL), and 500 μg/mL geneticin in 5% CO2 at 37° C. Cells were passaged frequently, every 3-5 days, to avoid overgrowth, depletion of essential medium components, or acidic medium exposure. Cells were passaged using a brief wash in 0.05% trypsin with 1 mM EDTA, followed by dissociation in divalent-free phosphate-buffered saline (Hyclone #SH30028.02). Dissociated cells were seeded onto poly-D-lysine coated black-walled 96-well plates (Biocoat; Becton Dickinson #354640) at about 40,000 cells per well and grown for approximately 1 day in culture medium to near confluency. The assay buffer was composed of 130 mM NaCl, 2 mM KCl, 2 mM MgCl2, 10 mM HEPES, 5 mM glucose, and either 2 mM or 20 μM CaCl2. On the day of the experiment, the culture medium was replaced with 2 mM calcium assay buffer using an automated plate washer (ELx405; Biotek, VT). The cells were incubated in 100 μL/well Fluo-3/AM (2 μM; TEFLabs #0116) with Pluronic F127 (100 μg/mL; Sigma #P2443) for 1 h at rt in the dark. After loading the cells, the dye solution was replaced with 50 μL/well of 20 μM calcium assay buffer using the ELx405 plate washer. Test compounds (50 μL/well) were added to the plate and incubated for 30 min. Intracellular Ca2+ levels were subsequently assayed using a Fluorometric Imaging Plate Reader (FLIPR™ instrument, Molecular Devices, CA) to simultaneously monitor Fluo-3 fluorescence in all wells (λexcitation=488 nm, λemission=540 nm) during challenge with agonist (capsaicin). The IC50 values were determined. Cells were challenged with 150 nM capsaicin and the fluorescence counts were captured following agonist addition at a sampling rate of 0.33 Hz. The contents of the wells were mixed 3 times (40 μL mix volume) immediately after the additions were made. Concentration dependence of block was determined by exposing each well of cells in duplicate rows of a 96 well plate to a serial dilution of test compound. The concentration series usually started at 10 Î¼M with a three-fold serial decrement in concentration. The magnitude of the capsaicin response was determined by measuring the change in fluo3 fluorescence before and 100 seconds after the addition of the agonist.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 537.59, ALogP 4.88, HBA 8, HBD 1, PSA 90.2, QED 0.49
Compound (SMILES): O=C1O[C@]2(CC[C@H](c3nc4cc(OC(F)(F)F)ccc4[nH]3)CC2)CN1c1ccccc1
InChIKey: KDNNOONPIUSODK-HNSKJHPRSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay
Measurement: Ki = 0.3162 nM (pChEMBL 9.5)
Descriptors: MW 431.41, ALogP 5.51, HBA 4, HBD 1, PSA 67.45, QED 0.59
Compound (SMILES): O=C1O[C@]2(CC[C@H](c3nc4cc(OC(F)(F)F)ccc4[nH]3)CC2)CN1c1ccccc1F
InChIKey: FFHHVAVTPWLQJT-KIFPSNHUSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay
Measurement: Ki = 0.631 nM (pChEMBL 9.199999809265137)
Descriptors: MW 449.4, ALogP 5.65, HBA 4, HBD 1, PSA 67.45, QED 0.52
Compound (SMILES): Cc1ccc2c(N3CCN(CCc4c(C)ccc5c4ccc(=O)n5C)CC3)cc(F)cc2n1
InChIKey: HRWBYOOBXRZGGR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide in human hERG expressed in CHO cells by proximity assay
Measurement: Ki = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 444.55, ALogP 4.21, HBA 5, HBD 0, PSA 41.37, QED 0.47
Compound (SMILES): Cc1ccc2c(N3CCN(CCc4c(C)ccc5c4ccc(=O)n5C)[C@H](C)C3)cccc2n1
InChIKey: UUWQIBYZFVEIMA-OAQYLSRUSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide in human hERG expressed in CHO cells by proximity assay
Measurement: Ki = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 440.59, ALogP 4.46, HBA 5, HBD 0, PSA 41.37, QED 0.47
Compound (SMILES): O=c1cc(OCc2ccccc2)ccn1-c1ccc2c(cnn2CCN2CCCC2)c1
InChIKey: QBYYFLZCKXHEJS-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 414.51, ALogP 3.86, HBA 6, HBD 0, PSA 52.29, QED 0.46
Compound (SMILES): CN1CCC(C(=O)OCc2ccc(Br)cc2)(c2ccc(Cl)c(Cl)c2)CC1.Cl
InChIKey: DSYWUPDRIKZOSH-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Displacement of [3H]nisoxetine from norepinephrine transporter in Sprague-Dawley rat frontal cortex after 1 hr by liquid scintillation counting
Measurement: Ki = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 457.2, ALogP 5.46, HBA 3, HBD 0, PSA 29.54, QED 0.57
Compound (SMILES): CCC(NC(=O)c1cccc(C(F)(F)F)c1Cl)C(=O)C(=O)Nc1cc[nH]n1
InChIKey: VKQOQWWJCCFELL-UHFFFAOYSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B by fluorescence assay
Measurement: IC50 = 5754 nM (pChEMBL 5.239999771118164)
Descriptors: MW 402.76, ALogP 2.8, HBA 4, HBD 3, PSA 103.95, QED 0.65
Compound (SMILES): CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CN=[N+]=[N-])OC(C(=O)O)=C[C@@H]1O
InChIKey: ALVXTNDDVFJVAI-UFGQHTETSA-N
Target: Sialidase (SINGLE PROTEIN), Clostridium perfringens
UniProt: P10481
Assay: Inhibition of Clostridium perfringens sialidase using Neu5Acalpha2-3GalbetapNP as substrate after 30 mins by colorimetric assay
Measurement: IC50 = 59000 nM (pChEMBL 4.230000019073486)
Descriptors: MW 316.27, ALogP -1.75, HBA 7, HBD 5, PSA 185.08, QED 0.22
Compound (SMILES): CN(O)C(=O)c1cc2c(CN3CCC[C@H]3C(N)=O)cn(Cc3ccc(F)cc3)c2cn1
InChIKey: XGYYVDZJWSDWDE-IBGZPJMESA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 425.46, ALogP 2.13, HBA 6, HBD 2, PSA 104.69, QED 0.47
Compound (SMILES): CCO[C@H]1CN([C@H]2CC[C@@](O)(c3ccc4c(c3)OCO4)CC2)C[C@@H]1NC(=O)CNC(=O)c1cccc(C(F)(F)F)c1
InChIKey: MZEOSVPWMSEFPW-UTWBDPIXSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at human CCR2 assessed as inhibition of MCP1 induced chemotaxis after 30 mins
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 577.6, ALogP 3.2, HBA 7, HBD 3, PSA 109.36, QED 0.44
Compound (SMILES): CCC(O)(c1cn(Cc2ccc3c(-c4ccccc4)c(C(=O)N(C)C)sc3c2)nn1)C(F)(F)F
InChIKey: DQXXWUPHDARIPI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of labeled MK-499 from human ERG
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 488.54, ALogP 5.07, HBA 6, HBD 1, PSA 71.25, QED 0.41
Compound (SMILES): CCC(O)(c1cn(Cc2ccc3c(-c4ccccc4)c(C(=O)NC)sc3c2)nn1)C(F)(F)F
InChIKey: OGPQDWMXVJCSIW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of labeled MK-499 from human ERG
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 474.51, ALogP 4.73, HBA 6, HBD 2, PSA 80.04, QED 0.42
Compound (SMILES): CN(Cc1ccc(Cl)c(Cl)c1)C(=O)COc1ccc2[nH]c(=O)c(S(C)(=O)=O)c(CCc3ccccc3)c2c1
InChIKey: JTSYTEBKLVVQPE-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor transfected in CHO cells assessed as inhibition of NECA-induced cAMP accumulation treated 15 mins before NECA challenge measured after 1 hr
Measurement: Ki = 1017 nM (pChEMBL 5.989999771118164)
Descriptors: MW 573.5, ALogP 5.06, HBA 5, HBD 1, PSA 96.54, QED 0.3