lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCc1cc2nccc(Nc3n[nH]c(C)c3C)c2cc1S(=O)(=O)C(C)(C)C
InChIKey: ZANVLEPAQZKAAQ-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of RIPK2 in human whole blood assessed as reduction in MDP-stimulated TNFalpha levels incubated for 30 mins followed by MDP addition measured after 5 hrs
Measurement: IC50 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 386.52, ALogP 4.45, HBA 5, HBD 2, PSA 87.74, QED 0.69
Compound (SMILES): CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1NC(=S)NCCN([C@@H](C(=O)O)C(C)C)S(=O)(=O)c1ccc(-c2ccccc2)cc1
InChIKey: NZFBENDBEOZJMI-KNWPELBISA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence assay
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 638.77, ALogP -0.14, HBA 9, HBD 7, PSA 197.76, QED 0.15
Compound (SMILES): O=C1[C@@H]2[C@H](C(=O)N1CCCCN1CCN(c3cccc4c3OCCO4)CC1)[C@H]1C=C[C@@H]2C1
InChIKey: OBKOPYWWTQOWFZ-MTIDIVMFSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5-HT1A receptor (unknown origin) after 60 mins by Ultra lance cAMP assay
Measurement: EC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 437.54, ALogP 2.17, HBA 6, HBD 0, PSA 62.32, QED 0.39
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc3cn[nH]c3c2)c1
InChIKey: LLIMXLUTGJVMBY-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 335.32, ALogP 2.42, HBA 6, HBD 2, PSA 105.92, QED 0.58
Compound (SMILES): CNc1cc(Nc2cccc3c2OCCO3)nn2c(C(=O)NC3CC3)cnc12
InChIKey: NSKLPBZBZREBGV-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IL23-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 380.41, ALogP 2.18, HBA 8, HBD 3, PSA 101.81, QED 0.62
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(C(=O)C4CCOCC4)CC3)n2c1)S(C)(=O)=O
InChIKey: BGFNEVWDENTDFC-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P11168
Assay: Inhibition of human GluT2 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 580.54, ALogP 3.77, HBA 7, HBD 0, PSA 87.46, QED 0.44
Compound (SMILES): Clc1ccc(-c2nc3ccc(-c4ccccn4)cn3c2CN2CCn3ncnc3C2)c(Cl)c1
InChIKey: ZQYZZIQSTRNTAZ-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P11168
Assay: Inhibition of human GluT2 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 476.37, ALogP 4.98, HBA 7, HBD 0, PSA 64.14, QED 0.37
Compound (SMILES): Cc1ccccc1NC(=O)Nc1cc(S(N)(=O)=O)ccc1O
InChIKey: JJLVFDGUWKZSRI-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 136.9 nM (pChEMBL 6.860000133514404)
Descriptors: MW 321.36, ALogP 1.99, HBA 4, HBD 4, PSA 121.52, QED 0.65
Compound (SMILES): COc1cc2c(Nc3ccc(F)c(Cl)c3)c(N)oc2c(C)n1
InChIKey: AXMSFVPTAZTCDK-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 15 mins by UV-vis HPLC analysis
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 321.74, ALogP 4.26, HBA 5, HBD 2, PSA 73.31, QED 0.75
Compound (SMILES): COC(=O)N1CCC[C@H]1CC(=O)N(c1cccc(F)c1)[C@H](C(=O)NC1CC(F)(F)C1)c1ccccc1Cl
InChIKey: FIFCCTHHVVJDQX-MBSDFSHPSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant in human HT1080 cells assessed as reduction in 2-hydroxyglutarate production by LC-MS/MS analysis
Measurement: IC50 = 279 nM (pChEMBL 6.550000190734863)
Descriptors: MW 537.97, ALogP 5.09, HBA 4, HBD 1, PSA 78.95, QED 0.53
Compound (SMILES): Nc1oc2c(-c3ccncc3)nccc2c1Nc1ccccc1Cl
InChIKey: XTKSVVQZAHYCGX-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 15 mins by UV-vis HPLC analysis
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 336.78, ALogP 4.87, HBA 5, HBD 2, PSA 76.97, QED 0.56
Compound (SMILES): Cn1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(CC3COC3)c2=O)cn1
InChIKey: VBAAHLXSBGINKC-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of human full length PARG using Bt-NAD ribosylated PARP1 substrate after 10 mins by TR-FRET assay
Measurement: EC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 459.53, ALogP 0.42, HBA 9, HBD 1, PSA 117.22, QED 0.55
Compound (SMILES): CCCCC(CCCC(=O)Nc1ccccc1)CCC(=O)NO
InChIKey: UVXBKULTGDABJT-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 in human HeLa-S3 cell lysates preincubated for 15 mins followed by HDAC-Glo substrate addition measured after 30 to 40 mins by fluorimetric method
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 320.43, ALogP 3.89, HBA 3, HBD 3, PSA 78.43, QED 0.43
Compound (SMILES): CC(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H]1CCC[C@@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H]1CNC[C@@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H]1CCC[C@@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NC(CCCCN)CC(=O)N[C@@H](CCCCN)C(=O)NCC(=O)NCCC(=O)N[C@H](C(=O)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C
InChIKey: CHSVVUUWJXNQLO-XKOVSAHMSA-N
Target: Vasoactive intestinal polypeptide receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32241
Assay: Agonist activity at human VIPR1 expressed in CHOK1 cells assessed as intracellular cAMP accumulation after 60 mins by PathHunter assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 3615.16
Compound (SMILES): Nc1oc2c(I)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: BQQCMWQJYJYNEA-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 15 mins by UV-vis HPLC analysis
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 403.58, ALogP 4.55, HBA 4, HBD 2, PSA 64.08, QED 0.49
Compound (SMILES): CO[C@H]1C[C@H](O[C@H]2CC[C@@]3(C)[C@H](CC[C@@H]4[C@@H]3CC[C@]3(C)[C@@H](C5=CC(=O)OC5)[C@@H](OC(C)=O)C[C@]43O)C2)O[C@@H](C)[C@@H]1O
InChIKey: JLPDBLFIVFSOCC-XYXFTTADSA-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 576.73, ALogP 3.68, HBA 9, HBD 2, PSA 120.75, QED 0.37
Compound (SMILES): CCOC(=O)c1cnc(NN)n2nc(-c3ccco3)nc12
InChIKey: LZRJTCLKARXZBF-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]NECA from human adenosine A2A receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 288.27, ALogP 0.85, HBA 9, HBD 2, PSA 120.57, QED 0.41
Compound (SMILES): Cl.O=C(CN1CCC(Cc2ccccc2)CC1)c1ccc2ccccc2c1
InChIKey: QAIYCEDWESWDID-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-DTG from S2R in rat liver membranes after 120 mins by scintillation counting assay
Measurement: Ki = 802 nM (pChEMBL 6.099999904632568)
Descriptors: MW 343.47, ALogP 4.98, HBA 2, HBD 0, PSA 20.31, QED 0.61
Compound (SMILES): O=C(NCCC1CCN(Cc2ccccc2)CC1)c1cc(=O)c2cccc(O)c2[nH]1
InChIKey: AZLXAYYWUXDYQA-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE expressed in HEK293 cells using acetylthiocholine iodide as substrate pretreated for 5 mins followed by substrate addition and measured for 5 mins by Ellman's method
Measurement: IC50 = 1150 nM (pChEMBL 5.940000057220459)
Descriptors: MW 405.5, ALogP 3.27, HBA 4, HBD 3, PSA 85.43, QED 0.59
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCOCCOCCn3cc(CN(CCOc4ccc5c(=O)cc(-c6ccccc6)oc5c4)Cc4ccccc4)nn3)ccc12
InChIKey: CHFFBBULXRPOLU-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP in human MCF7/MX100 cells assessed as reversal of topotecan resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 804.9, ALogP 8.02, HBA 12, HBD 0, PSA 131.29, QED 0.07
Compound (SMILES): O=C(O)c1ccc(N2CC3(CCN(Cc4cc(C(F)(F)F)c(Cl)cc4C4CC4)CC3)OC2=O)cc1
InChIKey: BZFUCKCMPOQIKK-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Antagonist activity at human SSR5 expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin addition measured after 1 hr by LANCE assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 508.92, ALogP 5.93, HBA 4, HBD 1, PSA 70.08, QED 0.54
Compound (SMILES): CCOC(=O)c1c(-c2ccc(Br)cc2F)oc2c1cc(O)c1ccccc12
InChIKey: SWGUNYVTLAITNK-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5-LO expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 15 mins followed by substrate addition measured after 10 mins by RP-HPLC analysis
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 429.24, ALogP 6.04, HBA 4, HBD 1, PSA 59.67, QED 0.4
Compound (SMILES): O=c1c2ccccc2nc(SCc2cn(-c3ccc(Cl)cc3)nn2)n1-c1ccccc1
InChIKey: ZUZSBORTLQISNS-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of recombinant human COX2 assessed as reduction in PGF2alpha production using arachidonic acid as substrate by colorimetric method
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 445.94, ALogP 4.91, HBA 7, HBD 0, PSA 65.6, QED 0.28
Compound (SMILES): Cn1nnc(-c2ccnc(-c3cn(Cc4ccccc4Cl)cn3)c2)n1
InChIKey: LULNZVARULNQAH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 351.8, ALogP 2.84, HBA 7, HBD 0, PSA 74.31, QED 0.56
Compound (SMILES): CCCC1NCCc2cc(-c3nc4c(C(N)=O)cc(F)cc4[nH]3)sc21
InChIKey: HNVGNPZHTCPRJL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of recombinant human PARP1 using histone as substrate after 1 hr in presence of NAD+ by ELISA
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 358.44, ALogP 3.52, HBA 4, HBD 3, PSA 83.8, QED 0.67
Compound (SMILES): Nc1oc2cnccc2c1Nc1cc(F)c(F)c(Br)c1
InChIKey: JPXLTWOBOAVJQR-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 15 mins by UV-vis HPLC analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 340.13, ALogP 4.19, HBA 4, HBD 2, PSA 64.08, QED 0.69
Compound (SMILES): Cc1ccc(C(=O)c2nc(Nc3cc(C)[nH]n3)c3ccc(Cl)cc3n2)cc1
InChIKey: XZQZGIIDBZOCRI-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using FAM-labelled peptide as substrate pretreated for 10 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 377.83, ALogP 4.6, HBA 5, HBD 2, PSA 83.56, QED 0.51
Compound (SMILES): CN1C(=N)N[C@@]2(c3cc(-c4cccc(C#N)c4)cs3)CN(c3ncc(F)c(N4CCCC4)n3)C[C@H]2C1=O
InChIKey: JVJQSMKMSLCKCB-SIBVEZHUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant human BACE1 expressed in HEK293 cells
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 516.61, ALogP 3.14, HBA 8, HBD 2, PSA 112.24, QED 0.55
Compound (SMILES): Cl.O=C(NCCCCN1CCN(c2cccc(Cl)c2Cl)CC1)c1cc2ccccc2[nH]1
InChIKey: QNFFQBKCWVJYON-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-sulpiride from human D2 receptor expressed in HEK293 cells after 150 mins by liquid scintillation counting method
Measurement: Ki = 202.3 nM (pChEMBL 6.690000057220459)
Descriptors: MW 445.39, ALogP 4.81, HBA 3, HBD 2, PSA 51.37, QED 0.51
Compound (SMILES): CNc1ncc(C(=O)NCc2ccc(-c3ccccc3)cc2)c2nc(-c3ccco3)nn12
InChIKey: LRBRBZRXARFWFP-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from human adenosine A1 receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 424.46, ALogP 4.02, HBA 7, HBD 2, PSA 97.35, QED 0.43
Compound (SMILES): COc1cc(C)c(Cc2cc3c(s2)CCN(C(=O)c2nccs2)C3)cc1[C@@H]1O[C@H](CO)[C@@H](F)[C@H](O)[C@H]1O
InChIKey: BLFZECRQISKCID-ZXGKGEBGSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition of human kidneyl SGLT2 expressed in CHOK1 cells assessed as reduction in Na-dependent [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition measured after 2 hrs by TopCount method
Measurement: IC50 = 23.2 nM (pChEMBL 7.630000114440918)
Descriptors: MW 548.66, ALogP 2.8, HBA 9, HBD 3, PSA 112.35, QED 0.43
Compound (SMILES): CN1CCN(C2CCN(C(=O)COc3ccc(-c4ccccc4)cc3)CC2)CC1
InChIKey: MOQQZFPQHVEHKY-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Anopheles gambiae
UniProt: Q869C3
Assay: Inhibition of recombinant Anopheles gambiae AChE1 expressed in sf9 insect cells using acetylthiocholine iodide as substrate measured over 60 secs by Ellman assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 393.53, ALogP 2.97, HBA 4, HBD 0, PSA 36.02, QED 0.78
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2Cc2ccccc2)c1
InChIKey: SAXXFJQUHSPIPP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 279.3, ALogP 2.56, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): C=CCOC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1OC(=O)[C@H]1[C@@H](C)CC)C(C)C)C(C)C
InChIKey: HCQRRPYERGCDMA-QUSNUVHPSA-N
Target: Proteasome subunit beta type-1 (SINGLE PROTEIN), Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
UniProt: P38624
Assay: Inhibition of yeast 20S proteasome beta1 subunit using fluorescent substrate pretreated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 779 nM (pChEMBL 6.110000133514404)
Descriptors: MW 410.51, ALogP 1.58, HBA 6, HBD 2, PSA 110.8, QED 0.4
Compound (SMILES): COc1cccc(C(=O)NCCCCN2CCc3cc(OC)c(O)cc3C2)c1
InChIKey: BFQHXMFESCIHFB-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-Methylspiperone from human dopamine D4 receptor expressed in HEK cell membranes
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 384.48, ALogP 2.98, HBA 5, HBD 2, PSA 71.03, QED 0.68
Compound (SMILES): c1cc(CN2CCCCC2)cc(-c2ccc(NCCCN3CCCCC3)c(OCCN3CCCCC3)c2)c1
InChIKey: DHZLVNXOHIHHEV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human SH-SY5Y cells harboring wild type APP695 assessed as reduction in amyloid beta (1 to 42) level after 24 hrs by ELISA method
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 518.79, ALogP 6.49, HBA 5, HBD 1, PSA 30.98, QED 0.32
Compound (SMILES): Cc1cc(C)cc(Nc2cc(Nc3ccccc3)c3ncc(C(N)=O)n3n2)c1
InChIKey: IFEXEXRVVLLXPF-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IL23-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 372.43, ALogP 3.93, HBA 6, HBD 3, PSA 97.34, QED 0.49
Compound (SMILES): Cc1ccc(C2=Nc3c(n[nH]c3C)Nc3nc(NC(C)(C)C)ncc32)cc1
InChIKey: QTJFIGDMMIYLER-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using STK S2 as substrate after 40 mins by HTRF assay
Measurement: IC50 = 356.5 nM (pChEMBL 6.449999809265137)
Descriptors: MW 361.45, ALogP 4.25, HBA 6, HBD 3, PSA 90.88, QED 0.5
Compound (SMILES): Cc1nn(C(=O)OC(C)(C)C)c(N)c1-c1ccc(Cl)c(Cl)c1
InChIKey: CTCULZLBPOLAKH-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged IKKepsilon (M1 to V716 residues) expressed in Sf9 insect cells using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 342.23, ALogP 4.53, HBA 5, HBD 1, PSA 70.14, QED 0.83
Compound (SMILES): CCOC(=O)C1=C(CSc2nc3cc([N+](=O)[O-])ccc3[nH]2)N(C)C(=O)NC1c1ccccc1
InChIKey: SWCCNBKDIDJPGU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) incubated for 1 hr by ELISA
Measurement: IC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 467.51, ALogP 3.78, HBA 7, HBD 2, PSA 130.46, QED 0.23
Compound (SMILES): Cc1nc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)co1
InChIKey: YBHPSBQYBQRDEV-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132C mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presence of NADPH and 30 uM NADP ny fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 372.33, ALogP 3.25, HBA 7, HBD 2, PSA 88.76, QED 0.78
Compound (SMILES): O=C(Nc1ccc(F)cc1)c1sccc1Nc1cccc2c1OCCO2
InChIKey: PMUBRDNCIWKVPM-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of ABCB1 efflux pump in human LS180 cells using Rh123 as substrate incubated for 90 mins by fluorescence based assay
Measurement: EC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 370.41, ALogP 4.65, HBA 5, HBD 2, PSA 59.59, QED 0.7
Compound (SMILES): N#CC1(c2cc(Nc3nc(NC4CCC(F)(F)CC4)nc(-n4ccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: POHHIURFWMYFGA-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 505.46, ALogP 4.76, HBA 9, HBD 2, PSA 117.23, QED 0.46
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H]3C(=O)N(C)CC(=O)N23)s1
InChIKey: WNVDDMMDUVNDAO-OXQOHEQNSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P54750
Assay: Inhibition of full length recombinant human N-terminal GST-tagged PDE1A expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 379.49, ALogP 3.11, HBA 3, HBD 1, PSA 56.41, QED 0.74
Compound (SMILES): CCc1nccc2c(Nc3cccc(C(F)(F)F)c3)c(N)oc12
InChIKey: KUJVWFVTDJCVDN-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 15 mins by UV-vis HPLC analysis
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 321.3, ALogP 4.73, HBA 4, HBD 2, PSA 64.08, QED 0.73
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2ccccc2F)n1)C1CC1
InChIKey: SBWSJSCKQBEYEK-VXGBXAGGSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132C mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 90 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 341.43, ALogP 4.1, HBA 5, HBD 2, PSA 62.73, QED 0.79
Compound (SMILES): Fc1ccc(-c2c(-c3cc(-c4nn[nH]n4)ccn3)ncn2CC2CC2)cc1
InChIKey: KCJJYCIVFYDIRB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 361.38, ALogP 3.34, HBA 6, HBD 1, PSA 85.17, QED 0.59
Compound (SMILES): C[C@@H](CC(=O)N1CCC(O)(Cn2cnc3c(-c4ccc(CN)cc4)n(C)nc3c2=O)CC1)c1ccccc1
InChIKey: DGHAUZFDWIZFRM-FQEVSTJZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using Ub-Rho110 as substrate by SPR analysis
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 514.63, ALogP 2.8, HBA 8, HBD 2, PSA 119.27, QED 0.39
Compound (SMILES): CCCCc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: YHNFXISQPODBJA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 245.28, ALogP 2.31, HBA 4, HBD 1, PSA 68.01, QED 0.88
Compound (SMILES): CCOC(=O)c1nn(C)c2c1C(C)Cc1cnc(Nc3ccccc3)nc1-2
InChIKey: BSIPNJIOPDWDSK-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK4/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.42, ALogP 3.46, HBA 7, HBD 1, PSA 81.93, QED 0.72
Compound (SMILES): O=S(=O)(Nc1nnc2cc(OCC34CC5CC(CC(C5)C3)C4)c(C3CC3)cn12)C1CCC1
InChIKey: SVPCWDMKWCXQFX-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay (EP) (In Vitro Assay): The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured using the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaC12, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaC12, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. In some studies, the external sodium was reduced by equimolar replacement with choline. Osmolarity in the CsF internal and NaCl external solutions was adjusted to 300 mOsm/kg and 310 mOsm/kg with glucose, respectively. All recordings were performed at ambient temperature in a bath chamber with a volume of 150 μL. Control sodium currents were measured in 0.5% DMSO. Controls and representative compounds of the invention were applied to the recording chamber through a 4-pinch or 8-pinch valve bath perfusion system manufactured by ALA Scientific Instruments.
Measurement: IC50 = 7.54 nM (pChEMBL 8.119999885559082)
Descriptors: MW 456.61, ALogP 4.5, HBA 6, HBD 1, PSA 85.59, QED 0.66
Compound (SMILES): O=S(=O)(CCCCl)N1CCN(c2ccc(/C=C/c3cc(Cl)cc(Cn4ccnc4)c3)cc2)CC1
InChIKey: BEEQSJMIBJVSRU-NSCUHMNNSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of recombinant CYP11B1 (unknown origin) expressed in human AD293 cells using 11-deoxycortisol as substrate pretreated for 60 mins followed by substrate addition and measured after 12 hrs by LC/MS analysis
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 519.5, ALogP 4.84, HBA 5, HBD 0, PSA 58.44, QED 0.3
Compound (SMILES): CCOC(=O)c1c(-c2ccc(Cl)c(Cl)c2)[nH]c2c1cc(O)c1ccccc12
InChIKey: WEIJKEYQWOSYEJ-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5-LO expressed in Escherichia coli BL21 using arachidonic acid as substrate preincubated for 15 mins followed by substrate addition measured after 10 mins by RP-HPLC analysis
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 400.26, ALogP 6.18, HBA 3, HBD 2, PSA 62.32, QED 0.4
Compound (SMILES): CCOC(=O)c1cnc(N2CCNCC2)n2nc(-c3ccco3)nc12
InChIKey: VZYYRUGCZSBASL-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]NECA from human adenosine A2A receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.36, ALogP 0.97, HBA 9, HBD 1, PSA 97.79, QED 0.7
Compound (SMILES): O=C(c1ccc(-c2ccc3cccnc3c2)s1)c1cc(F)c(F)c(O)c1F
InChIKey: JNAXHYFRIIJSMB-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 385.37, ALogP 5.32, HBA 4, HBD 1, PSA 50.19, QED 0.38
Compound (SMILES): Cn1c(=O)c(=O)n(C)c2cc(N3CCOCC3)c(NS(=O)(=O)c3ccc4c(c3)CCCC4)cc21
InChIKey: HKFDPIBCGYGLOO-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to N-terminal GST-tagged BRPF1 (unknown origin) expressed in Escherichia coli by isothermal titration calorimetry
Measurement: Kd = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 484.58, ALogP 1.75, HBA 8, HBD 1, PSA 102.64, QED 0.57
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc(F)c(-c4cc(F)c5c(c4)C4(CCCC4)C(C)=N5)n3)nc2)CC1
InChIKey: FOLRMJVSUYSNKR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/Cyclin-D1 (unknown origin) using histone-H1 as substrate after 90 mins by ADP-Glo assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 503.6, ALogP 5.62, HBA 7, HBD 1, PSA 69.54, QED 0.49
Compound (SMILES): Cc1cc(-c2ccc3c(c2)CCC3N2CCC(N(C)C(=O)N[C@@H](CC3CC3)c3cccc(Cl)c3Cl)CC2)ncn1
InChIKey: IAOSWRKSTBNXKT-UFXYQILXSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Inverse agonist at recombinant human GHSR1a expressed in HEK293 cells assessed as decrease in IP1 accumulation after 1 hr by IP1-d2-based HTRF assay
Measurement: EC50 = 970 nM (pChEMBL 6.010000228881836)
Descriptors: MW 578.59, ALogP 7.39, HBA 4, HBD 1, PSA 61.36, QED 0.32
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)c1ccc(Cl)cc1
InChIKey: LYECZDRRRZNARD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 356.81, ALogP 3.43, HBA 5, HBD 1, PSA 71.25, QED 0.73
Compound (SMILES): CC[C@H](C(=O)N1CC(C#N)C1)n1c(=O)c2cc(OC)c(OC)cc2c2cnc3[nH]ccc3c21
InChIKey: ZDNBWZRRFSXDFS-GOSISDBHSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter-binding method
Measurement: IC50 = 114.4 nM (pChEMBL 6.940000057220459)
Descriptors: MW 445.48, ALogP 2.98, HBA 7, HBD 1, PSA 113.24, QED 0.47
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2(S(C)(=O)=O)CC2)nc(-n2c(N)nc3cc(F)ccc32)n1
InChIKey: YOHWFCAJLSLBIS-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT29 cells after 60 mins by Hoechst 33258 staining-based assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 446.51, ALogP 1.8, HBA 9, HBD 1, PSA 116.23, QED 0.64
Compound (SMILES): COc1ccc2cnccc2c1-c1ccc(Oc2nccc3occc23)cc1
InChIKey: IYKSDQDBJIYZDN-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]-SCH23390 from human dopamine D1 receptor expressed in LTK cell membranes after 30 mins by liquid scintillation counting
Measurement: Ki = 56.3 nM (pChEMBL 7.25)
Descriptors: MW 368.39, ALogP 5.84, HBA 5, HBD 0, PSA 57.38, QED 0.4
Compound (SMILES): CCc1cn2c(NS(C)(=O)=O)nnc2cc1OCC12CC3CC(CC(C3)C1)C2
InChIKey: ZDVPWQBMSWEBJS-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay (EP) (In Vitro Assay): The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured using the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaC12, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaC12, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. In some studies, the external sodium was reduced by equimolar replacement with choline. Osmolarity in the CsF internal and NaCl external solutions was adjusted to 300 mOsm/kg and 310 mOsm/kg with glucose, respectively. All recordings were performed at ambient temperature in a bath chamber with a volume of 150 μL. Control sodium currents were measured in 0.5% DMSO. Controls and representative compounds of the invention were applied to the recording chamber through a 4-pinch or 8-pinch valve bath perfusion system manufactured by ALA Scientific Instruments.
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 404.54, ALogP 3.26, HBA 6, HBD 1, PSA 85.59, QED 0.8
Compound (SMILES): CC(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCc1ccc(C(=N)N)nc1)C(C)C
InChIKey: QAZHDINZSZMIJH-MHNGZOTISA-N
Target: Furin (SINGLE PROTEIN), Homo sapiens
UniProt: P09958
Assay: Inhibition of recombinant human furin using pGlu-Arg-Thr-Lys-Arg-AMC peptide as substrate by spectrofluorometry
Measurement: Ki = 21.5 nM (pChEMBL 7.670000076293945)
Descriptors: MW 1028.36
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3cc(-c4ccncc4)c[nH]c3=O)cc2)CC1
InChIKey: GPWFEKSGAWXQOP-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of full length N-terminal His-tagged Aurora A (unknown origin) using fluorescence-labeled FL-Peptide 21 as substrate after 60 mins in presence of ATP by fluorescence assay based Cheng-Prusoff equation analysis
Measurement: Ki = 14900 nM (pChEMBL 4.829999923706055)
Descriptors: MW 389.46, ALogP 2.44, HBA 5, HBD 2, PSA 81.33, QED 0.72
Compound (SMILES): O=C(Nc1ccncc1)c1ccc(COc2ccccc2Cl)cc1
InChIKey: VAHVWEIUWRWGMO-UHFFFAOYSA-N
Target: Acyl-CoA desaturase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P13516
Assay: Inhibition of mouse liver microsome SCD assessed as reduction in [3H]H2O production using stearoyl [9,10-3H]CoA as substrate in presence of NADH incubated for 30 mins by scintillation counting method
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 338.79, ALogP 4.57, HBA 3, HBD 1, PSA 51.22, QED 0.74
Compound (SMILES): Cc1ccc(COc2ccnn2-c2cc(C(=O)O)ccn2)cc1Cl
InChIKey: BJFOUULYELAMPD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 343.77, ALogP 3.51, HBA 5, HBD 1, PSA 77.24, QED 0.77
Compound (SMILES): CN1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(-c4ccccc4)cn23)CCC1=O
InChIKey: QGXURTLOPUYOGP-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P11168
Assay: Inhibition of human GluT2 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 444.97, ALogP 4.99, HBA 4, HBD 0, PSA 40.85, QED 0.45
Compound (SMILES): Cc1ccc(-c2c(N)n[nH]c2C)cc1
InChIKey: FIQXGADANMRLKW-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged IKKepsilon (M1 to V716 residues) expressed in Sf9 insect cells using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 187.25, ALogP 2.28, HBA 2, HBD 2, PSA 54.7, QED 0.72
Compound (SMILES): O=C(c1ccc(-c2ccc(O)c(F)c2)s1)c1cc(F)c(F)c(O)c1F
InChIKey: RHSYGXKEQBUHAC-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 368.31, ALogP 4.61, HBA 4, HBD 2, PSA 57.53, QED 0.4
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1OC(=O)[C@H]1C(C)C)C(=O)N[C@H](C(=O)OCc1ccccc1)C(C)C
InChIKey: NEQHFOKLQNEKPO-LWYYNNOASA-N
Target: Proteasome subunit beta type-1 (SINGLE PROTEIN), Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
UniProt: P38624
Assay: Inhibition of yeast 20S proteasome beta1 subunit using fluorescent substrate pretreated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 4178 nM (pChEMBL 5.380000114440918)
Descriptors: MW 446.54, ALogP 2.21, HBA 6, HBD 2, PSA 110.8, QED 0.53
Compound (SMILES): CN(CCc1cnn(-c2cc(C(=O)NC#N)ccn2)c1)Cc1ccc(F)cc1
InChIKey: QXPNFUDMDNCVJO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 378.41, ALogP 2.29, HBA 6, HBD 1, PSA 86.84, QED 0.5
Compound (SMILES): Cc1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(CC3CC3)c2=O)on1
InChIKey: BPNAFLANHVBAPX-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of human full length PARG using Bt-NAD ribosylated PARP1 substrate after 10 mins by TR-FRET assay
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 444.51, ALogP 1.75, HBA 8, HBD 1, PSA 116.2, QED 0.59
Compound (SMILES): CCCc1n[nH]c2c1C(c1ccc(O)cc1)C(C#N)=C(N)O2
InChIKey: VSLVXHGVRYHBFZ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04828
Assay: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay
Measurement: IC50 = 3510 nM (pChEMBL 5.460000038146973)
Descriptors: MW 296.33, ALogP 2.29, HBA 5, HBD 3, PSA 107.95, QED 0.8
Compound (SMILES): Cc1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(C)c2=O)no1
InChIKey: LKMZDHQXFZPFAZ-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 5190 nM (pChEMBL 5.289999961853027)
Descriptors: MW 404.45, ALogP 0.88, HBA 8, HBD 1, PSA 116.2, QED 0.67
Compound (SMILES): O=c1cc(Sc2ccc(-c3cccc(C(F)(F)F)c3)cc2)[nH]c(=O)n1O
InChIKey: XCRSZKWDHUVLFK-UHFFFAOYSA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04585
Assay: Inhibition of HIV1 reverse transcriptase polymerase activity using 18 nucleotide DNA primer and 100 nucleotide DNA template after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.35, ALogP 3.61, HBA 5, HBD 2, PSA 75.09, QED 0.54
Compound (SMILES): Fc1ccc2[nH]cc(CCCN3CCN(c4ccccc4-c4ccccc4)CC3)c2c1
InChIKey: IDAPODLHCQBQIS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from recombinant human 5-HT1A receptor expressed in HEK293 cell membranes after 60 mins by TopCount scintillation counting method
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 413.54, ALogP 5.73, HBA 2, HBD 1, PSA 22.27, QED 0.44
Compound (SMILES): N#Cc1c[nH]c(C(=O)Nc2ccc(CCN3CCOCC3)cc2C2=CCCCC2)n1.O=C(O)C(F)(F)F
InChIKey: XSOGEEANMVXODB-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Inhibition of c-fms in mouse bone marrow macrophages assessed as reduction in recombinant mouse CSF-1-driven cell proliferation by measuring bromodeoxyuridine incorporation incubated for 30 hrs by ELISA
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 405.5, ALogP 3.37, HBA 5, HBD 2, PSA 94.04, QED 0.77
Compound (SMILES): Cc1ccc2nccn2c1-c1ccc(Oc2nccc3occc23)cc1
InChIKey: PWLYFXFNLDFOGR-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]-SCH23390 from human dopamine D1 receptor expressed in LTK cell membranes after 30 mins by liquid scintillation counting
Measurement: Ki = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 341.37, ALogP 5.24, HBA 5, HBD 0, PSA 52.56, QED 0.45
Compound (SMILES): N#CC1(c2cc(Nc3nc(N[C@H]4CCC(F)(F)C4)nc(-c4ccnc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: WMHFZXFIAKEFCS-ZDUSSCGKSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 503.44, ALogP 4.64, HBA 9, HBD 2, PSA 125.19, QED 0.46
Compound (SMILES): Cn1cnc(-c2cc3[nH]nnc3cn2)c1-c1ccc(F)cc1
InChIKey: DFIZSWCEVFIDEP-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PHF8 expressed in baculovirus infected Sf9 cells using H3K9mel-biotin labelled peptide as substrate measured after 15 mins by Lance TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 294.29, ALogP 2.56, HBA 5, HBD 1, PSA 72.28, QED 0.62
Compound (SMILES): Clc1ccc(N2CCN(CCCCOc3ccc4ccccc4c3)CC2)c(Cl)c1
InChIKey: AWRLKRYSNLRLAB-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of [3H]serotonin uptake at human SERT expressed in HEK293 cells after 15 to 20 mins by microbeta scintillation counting method
Measurement: IC50 = 4320 nM (pChEMBL 5.369999885559082)
Descriptors: MW 429.39, ALogP 6.13, HBA 3, HBD 0, PSA 15.71, QED 0.42
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C(=O)Nc3ccccc3F)cc2)cc1
InChIKey: MEJYFHSTMVGYPM-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Transrepression of recombinant human GAL4-DBD fused RORgammat LBD expressed in HEK293 cells after 20 hrs by luciferase reporter gene assay
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 482.58, ALogP 4.72, HBA 4, HBD 2, PSA 92.34, QED 0.49
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C(=O)Nc3ncccc3F)cc2)cc1
InChIKey: JIHVDVKUIJBBOQ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: Transrepression of recombinant mouse GAL4-DBD fused RORgammat LBD expressed in HEK293 cells after 20 hrs by luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 483.57, ALogP 4.11, HBA 5, HBD 2, PSA 105.23, QED 0.5
Compound (SMILES): O=C1CN(Cc2c(-c3ccc(Cl)cc3Cl)nc3ccc(-c4ncon4)cn23)CCN1
InChIKey: BBVHPMWUMSSSPR-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P11168
Assay: Inhibition of human GluT2 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 443.29, ALogP 3.29, HBA 7, HBD 1, PSA 88.56, QED 0.52
Compound (SMILES): CC(=O)N[C@H]1CC[C@H](Nc2nccc(-c3c(-c4ccccc4)noc3C)n2)CC1
InChIKey: DLNGCNBJNSICSI-IYARVYRRSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human p38alpha using FAM-p38tide as substrate by IMAP assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 391.48, ALogP 3.97, HBA 6, HBD 2, PSA 92.94, QED 0.68
Compound (SMILES): O=C1Nc2ccccc2/C1=N/c1ccccc1Br
InChIKey: AIHFMODGKKPMHY-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO assessed as reduction in conversion of L-tryptophan to kynurenine by methylene blue dye based spectrometric method
Measurement: IC50 = 46240 nM (pChEMBL 4.329999923706055)
Descriptors: MW 301.14, ALogP 3.52, HBA 2, HBD 1, PSA 41.46, QED 0.86