lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H](O)CNc1cc(Oc2ccc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2)ncn1
InChIKey: BUJLMFKZIJWAPL-CYBMUJFWSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of GST-6His tagged VEGFR2 (unknown origin) using biotin-aminohexyl-EEEEYFELVAKKKK-NH2 peptide substrate incubated for 90 mins by HTRF assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 447.42, ALogP 4.72, HBA 6, HBD 4, PSA 108.4, QED 0.42
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cnn(Cc3ccccc3)c2)C[C@@H]1O
InChIKey: MUJHZPSIEOHDFE-SUMDDJOVSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13564
Assay: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 472.53, ALogP 0.72, HBA 10, HBD 3, PSA 162.32, QED 0.38
Compound (SMILES): CCC(C)C(NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)(C)C)P(=O)(Oc1ccccc1)Oc1ccccc1
InChIKey: AEZNOQJIMPKOLO-BEMTXIMASA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of human neutrophil elastase using methoxysuccinyl-Ala-Ala-Pro-Val-pNA as substrate incubated for 15 min
Measurement: IC50 = 2470 nM (pChEMBL 5.610000133514404)
Descriptors: MW 663.75, ALogP 7.16, HBA 7, HBD 2, PSA 123.27, QED 0.19
Compound (SMILES): Cc1ccc(S(=O)(=O)C(C)C(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: WIEVAFQHFJCKDN-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 382.46, ALogP 1.44, HBA 5, HBD 2, PSA 123.4, QED 0.81
Compound (SMILES): Cc1ccccc1-c1nnc(SSc2nnc(-c3ccccc3C)[nH]2)[nH]1
InChIKey: UEEFLJRFMVXPAX-UHFFFAOYSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Inhibition of recombinant human His-tagged DCN1 (58 to 259 residues) expressed in Escherichia coli BL21 (DE3) using MIKLFSLKQQKKEEESAGGTK-biotin as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 83.91 nM (pChEMBL 7.079999923706055)
Descriptors: MW 380.5, ALogP 4.67, HBA 6, HBD 2, PSA 83.14, QED 0.49
Compound (SMILES): COc1ccc(Cl)cc1S(=O)(=O)Nc1cccc(O)c1
InChIKey: HANZKKJFFHVTLY-UHFFFAOYSA-N
Target: Urea transporter 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97689
Assay: Inhibition of rat UT-B incubated for 15 mins
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 313.76, ALogP 2.86, HBA 4, HBD 2, PSA 75.63, QED 0.91
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: QOBNDKJEFZTTRA-ALPKVHQLSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12392
Assay: Inhibition of rat alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1667.86
Compound (SMILES): O=C(NC12CCC(CC1)CC2)c1nn(-c2c[n+]([O-])ccn2)c2c1CC1CCC2O1
InChIKey: JQQCJRADEDHJOH-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO-K1 cells assessed as increase in cAMP level incubated for 20 mins measured after 60 mins addition of cAMP detect reagent by HTRF analysis
Measurement: EC50 = 48.5 nM (pChEMBL 7.309999942779541)
Descriptors: MW 395.46, ALogP 2.13, HBA 6, HBD 1, PSA 95.98, QED 0.63
Compound (SMILES): COc1cc2nc(-c3ccccc3)cc(NCC3CCN(c4ncc(C(=O)NO)cn4)CC3)c2cc1OC
InChIKey: XUPMSHMBHAZMIA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human N-terminal GST-tagged HDAC6 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 514.59, ALogP 4.16, HBA 9, HBD 3, PSA 121.73, QED 0.24
Compound (SMILES): C/C(=C\CC/C(C)=C/CC[C@]1(C)CCc2c(C)c(O)c(C)c(C)c2O1)CCC=C(CO)CO
InChIKey: UUHVLERXBOHWNS-VIRYQLDASA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX in human PMNL assessed as reduction in 5-LOX product formation preincubated for 10 mins before addition of AA and A23187 and measured after 10 mins by RP-HPLC method
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 456.67, ALogP 6.55, HBA 4, HBD 3, PSA 69.92, QED 0.33
Compound (SMILES): CN(C)c1ccc2c(Oc3ccc(NC(=O)NCc4ccc(C(F)(F)F)nc4)cc3)ncnc2c1
InChIKey: ORYMWWSJZRCUSV-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of recombinant GST-AURKA (residues Ser123 to Ser401) (unknown origin) expressed in Sf9 insect cells using tetra(-LRRASLG) peptide as substrate incubated for 90 mins by ATP Kinase Glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 482.47, ALogP 5.22, HBA 6, HBD 2, PSA 92.27, QED 0.39
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)C2CCN2CCCCCCc2ccccc2-c2cnc1[nH]2
InChIKey: SJFTZOLNFLMULZ-QSAPEBAKSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 464.65, ALogP 5.35, HBA 4, HBD 2, PSA 78.09, QED 0.54
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)CNCCN1CCN(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: LJXMZZBRBMPIDI-KEYWGVPBSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 0.309 nM (pChEMBL 9.510000228881836)
Descriptors: MW 845.06, ALogP 0.92, HBA 11, HBD 8, PSA 237.43, QED 0.05
Compound (SMILES): O=C(N[C@@H](c1ccccc1)c1cccc(OCCCCCCNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)c1)O[C@H]1CN2CCC1CC2
InChIKey: DENKZAPZMPGKBS-IUKTVIPNSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of 125I-cyanopindolol from human adrenergic beta2 receptor
Measurement: Ki = 0.5012 nM (pChEMBL 9.300000190734863)
Descriptors: MW 654.81, ALogP 5.41, HBA 8, HBD 5, PSA 136.15, QED 0.11
Compound (SMILES): COc1ccc(OC)c(-n2nnc(S(=O)(=O)c3ccc(C)cc3)c2C)c1
InChIKey: DXYRRGYZBRAKFU-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs by luciferase reporter assay
Measurement: EC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 373.43, ALogP 2.73, HBA 7, HBD 0, PSA 83.31, QED 0.68
Compound (SMILES): CCN(CC)S(=O)(=O)c1ccc([C@H]2C[C@@H]2N)cc1
InChIKey: ZUPXTWCPGBCTFM-OLZOCXBDSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of MAO-A (unknown origin) preincubated for 20 mins using 5-hydroxytryptamine as substrate followed by substrate addition and measured after 60 mins
Measurement: IC50 = 806.5 nM (pChEMBL 6.090000152587891)
Descriptors: MW 268.38, ALogP 1.53, HBA 3, HBD 1, PSA 63.4, QED 0.88
Compound (SMILES): CCCc1[nH]c2nc(C)ncc2c1C#N
InChIKey: XTUZAZGRPVHGAJ-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16654
Assay: Inhibition of human PDHK4 co-complexed with porcine PDH using sodium pyruvate, coenzymeA and NAD as substrate preincubated with enzyme complex for 45 mins followed by ATP addition and then later incubated with substrate for 90 mins by absorption spectrophotometric assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 200.24, ALogP 2.09, HBA 3, HBD 1, PSA 65.36, QED 0.81
Compound (SMILES): NC(=O)C1CN(Cc2ccccc2I)c2ccccc2O1
InChIKey: SAJMURDBTHRPNC-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of His6-tagged/TEV fused SIRT2 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 394.21, ALogP 2.54, HBA 3, HBD 1, PSA 55.56, QED 0.81
Compound (SMILES): CCc1cccc(CC)c1-n1c(C)c(C(=O)NCC(C)C)cc(-c2nc(-c3ccc(Cl)cc3)cs2)c1=O
InChIKey: KBDVDEXIHBNYEP-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 5 mins by diaphorase/resazurin-coupled system
Measurement: IC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 534.13, ALogP 7.1, HBA 5, HBD 1, PSA 63.99, QED 0.26
Compound (SMILES): NS(=O)(=O)c1ccc(NCC(=O)N2CCN(Cc3ccc(Cl)cc3)CC2)cc1
InChIKey: XXFGJZBVWDJSND-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 78.1 nM (pChEMBL 7.110000133514404)
Descriptors: MW 422.94, ALogP 1.74, HBA 5, HBD 2, PSA 95.74, QED 0.74
Compound (SMILES): CCC(=O)N1CCN(c2cc(N3CCC(C)CC3)c(F)cc2[N+](=O)[O-])CC1
InChIKey: AMJZWDOOGCYVHS-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 174 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXC1
Assay: Inverse agonist activity at human GPR174 expressed in cells assessed as inhibition of CRE-luc reporter activity by measuring decrease in Gs-protein signalling activity
Measurement: EC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 378.45, ALogP 3.03, HBA 5, HBD 0, PSA 69.93, QED 0.59
Compound (SMILES): COc1ncc(-c2cc(O[C@@H]3CCN(C(=O)C4CC4)C3)cc3c2CNC3=O)cc1NS(C)(=O)=O
InChIKey: GJISQLYNRBQOQM-OAHLLOKOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) by HTRF assay
Measurement: IC50 = 315 nM (pChEMBL 6.5)
Descriptors: MW 486.55, ALogP 1.76, HBA 7, HBD 2, PSA 126.93, QED 0.61
Compound (SMILES): CCCCC1(c2cc(O)c3cc(CCC)c(=O)oc3c2)CCCCC1
InChIKey: SAQOBXZDPNLQSO-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-CP55940 from human recombinant CB1 receptor expressed in CHO-K1 cell membrane measured after 3 hrs by scintillation spectrometry
Measurement: Ki = 159 nM (pChEMBL 6.800000190734863)
Descriptors: MW 342.48, ALogP 5.84, HBA 3, HBD 1, PSA 50.44, QED 0.67
Compound (SMILES): Cc1ccccc1C(=O)N(CC(=O)NCc1ccccc1)Cc1ccc(C(=O)NO)cc1
InChIKey: MAIIMUAZGCLUNU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of N-terminal GST-tagged full length human recombinant HDAC6 expressed in baculovirus infected Sf9 cells using ZMAL (Z-Lys(Ac)-AMC) fluorogenic substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 431.49, ALogP 3.07, HBA 4, HBD 3, PSA 98.74, QED 0.38
Compound (SMILES): COc1ccccc1CNC[C@H](O)[C@H](Cc1ccccc1)NC(=O)CC(c1ccccc1)c1ccccc1
InChIKey: WOKVMEHUXJOESF-CONSDPRKSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by Ellman's method
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 508.66, ALogP 5.1, HBA 4, HBD 3, PSA 70.59, QED 0.24
Compound (SMILES): CC[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1CC[C@H](c2cccc(C(F)(F)F)n2)CC1
InChIKey: NDQJCJQXEZTZQF-IIDMSEBBSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse M109 cells preincubated for 2 hrs followed by recombinant murine IFNgamma stimulation and measured after 18 hrs by fluorescence based microplate reader assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 424.89, ALogP 6.24, HBA 2, HBD 1, PSA 41.99, QED 0.62
Compound (SMILES): CCOC(=O)/C(=N\Nc1ccccc1C(=O)OCC)C(=O)C(F)(F)F
InChIKey: AZFNOGDHVUHHHQ-JAIQZWGSSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 481 nM (pChEMBL 6.320000171661377)
Descriptors: MW 360.29, ALogP 2.33, HBA 7, HBD 1, PSA 94.06, QED 0.35
Compound (SMILES): C=Cc1ccc(Cn2nc(CCCc3ccc(OC(C)(C)C(=O)O)cc3)n(Cc3ccc(C)cc3)c2=O)cc1
InChIKey: RDLCIGKZXCHMHB-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPARalpha co-expressed with RXRalpha in monkey CV1 cells assessed as PPRE transcriptional activation incubated for 45 hrs by luciferase reporter gene assay
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 525.65, ALogP 5.51, HBA 6, HBD 1, PSA 86.35, QED 0.26
Compound (SMILES): O=C1NCc2c1cc(O[C@@H]1CCN(C(=O)C3CC3)C1)cc2-c1cncc(O)c1
InChIKey: WQCBXUPPFCPUGJ-OAHLLOKOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) by HTRF assay
Measurement: IC50 = 1020 nM (pChEMBL 5.989999771118164)
Descriptors: MW 379.42, ALogP 2.09, HBA 5, HBD 2, PSA 91.76, QED 0.85
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cccc(c1)C(=O)NCCn1cc(cn1)-c1cnc3ccc-2cn13
InChIKey: OYWBQBWKKZQNEG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human GST tagged mTOR (1360 to 2549 residues) expressed in baculovirus expression system measured by LanthaScreen assay
Measurement: IC50 = 5790 nM (pChEMBL 5.239999771118164)
Descriptors: MW 515.56, ALogP 2.81, HBA 9, HBD 2, PSA 132.51, QED 0.35
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(C#N)cc2)nc2c1CSCC2
InChIKey: GLFXFXOZHKJYEL-ONEGZZNKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 439.54, ALogP 5.83, HBA 7, HBD 1, PSA 94.62, QED 0.5
Compound (SMILES): CC(C)(C)c1noc(C(=O)NC2CCCc3cc(-c4ccnc5[nH]c(-c6cnn(C7CCOCC7)c6)nc45)ccc32)n1
InChIKey: WHASZSIQSYUKGT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 566.67, ALogP 5.33, HBA 9, HBD 2, PSA 136.64, QED 0.29
Compound (SMILES): Cc1ccccc1CCC(C)NCC(O)c1ccc(O)c2[nH]c(=O)ccc12.Cl
InChIKey: JXUXPJMAQCZLAG-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation
Measurement: EC50 = 0.01738 nM (pChEMBL 10.760000228881836)
Descriptors: MW 366.46, ALogP 3.19, HBA 4, HBD 4, PSA 85.35, QED 0.52
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CNc2ccc(OC(F)(F)F)cc2)cc1
InChIKey: RFQDKRNGGGLMNW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins measured by stopped flow CO2 hydration assay
Measurement: Ki = 298.8 nM (pChEMBL 6.53000020980835)
Descriptors: MW 403.38, ALogP 1.96, HBA 5, HBD 3, PSA 110.52, QED 0.65
Compound (SMILES): O=C(N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12)C1(O)CCCCC1
InChIKey: CBHXZNHHAYIMEF-PPJWLVRDSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at recombinant full-length human Gal4-fused RORgammat expressed in human Jurkat cells incubated for 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 639.61, ALogP 6.32, HBA 4, HBD 2, PSA 83.47, QED 0.3
Compound (SMILES): COc1ccc(C(C)NC(=O)/N=C(\N)NCCCc2sc(N)nc2C)cc1
InChIKey: HJLDSBZFVQXZLR-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor expressed in sf9 insect cell membranes co-expressing GSalphaS incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 37.15 nM (pChEMBL 7.429999828338623)
Descriptors: MW 390.51, ALogP 2.35, HBA 5, HBD 4, PSA 127.65, QED 0.33
Compound (SMILES): Cn1c(=O)[nH]c2c(Cl)cc3c(c21)CN(CC(F)(F)F)C(=O)[C@H](CC(=O)N1CCC(N2CCc4ccccc4NC2=O)CC1)C3
InChIKey: JXGSAMHWEISJEV-IBGZPJMESA-N
Target: Calcitonin gene-related peptide type 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16602
Assay: Antagonist activity against human CGRP receptor in human SK-N-MC cells assessed as inhibition of CGRP-stimulated cAMP production
Measurement: IC50 = 0.06 nM (pChEMBL 10.220000267028809)
Descriptors: MW 633.07, ALogP 4.05, HBA 5, HBD 2, PSA 110.75, QED 0.45
Compound (SMILES): Cc1c(Cc2cccs2)c(-c2cc(Cl)nc(N)n2)nn1C
InChIKey: JQJMCWHQDZMPPU-UHFFFAOYSA-N
Target: Adenylate cyclase type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PN6
Assay: Inhibition of human soluble adenylyl cyclase transfected (4-4 clones)in human HEK293 cells assessed as reduction in cAMP levels preincubated for 5 mins with test compounds in the presence of IBMX by ELISA
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 319.82, ALogP 3.07, HBA 6, HBD 1, PSA 69.62, QED 0.75
Compound (SMILES): Cc1cc(COc2ccc3c(c2)O/C(=C\c2ccc(C#N)cc2)C3=O)cc(C)c1OC(C)(C)C(=O)O
InChIKey: VPHDGIZKLYZNKF-MXAYSNPKSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human Gal4 fused PPARdelta LBD expressed in COS-7 cells incubated for 24 hrs by firefly luciferase reporter gene assay
Measurement: EC50 = 8940 nM (pChEMBL 5.050000190734863)
Descriptors: MW 483.52, ALogP 5.61, HBA 6, HBD 1, PSA 105.85, QED 0.44
Compound (SMILES): CC(=O)N1CCC(C(=O)N[C@@H]2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC1
InChIKey: JROACKQUEHWSEU-ZWEKWIFMSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at recombinant full-length human Gal4-fused RORgammat expressed in human Jurkat cells incubated for 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 666.63, ALogP 5.88, HBA 4, HBD 1, PSA 83.55, QED 0.32
Compound (SMILES): CCn1c(-c2ccc(C(F)(F)F)nc2)nc2c(O[C@H]3CCN(C(=O)C4CCOC4)C3)ncnc21
InChIKey: LHSYHMHXVQSGPJ-LOACHALJSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human Ramos cells assessed as reduction in anti-IgM-antibody-induced phosphorylation of AKT at Ser473 residue preincubated for 20 mins followed by anti-IgM antibody stimulation and measured after 30 mins by alphascreen assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 476.46, ALogP 2.94, HBA 8, HBD 0, PSA 95.26, QED 0.56
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc(C4CC4)n3)C[C@@H]21
InChIKey: HRARFWASJVNQSB-ASQHQMJYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 5 mins in presence of NADPH by LCMS/MS analysis
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 384.91, ALogP 4.21, HBA 4, HBD 1, PSA 59.81, QED 0.81
Compound (SMILES): COc1nc(C2=NOC(C3CC3)C(c3ccc(Cl)cc3)N2)ccc1-n1cnc(C)c1
InChIKey: IOQORVDNYPOZPL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 >= 14000 nM (pChEMBL 4.854000091552734)
Descriptors: MW 423.9, ALogP 4.04, HBA 7, HBD 1, PSA 73.56, QED 0.67
Compound (SMILES): CNC(=O)N1N=C(c2ccc(N3CCN(C(=O)CCCCNC(=O)COc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)cc2)c2cc(OC)c(OC)cc2C[C@@H]1C
InChIKey: MQPRRCLCHOSXND-RNWYOQHESA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of recombinant human His-tagged BRD4 BD2 using biotin-labelled histone H4 acetylated peptide as substrate by TR-FRET assay
Measurement: IC50 = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 850.93, ALogP 2.46, HBA 12, HBD 3, PSA 208.59, QED 0.17
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=S)Nc2ccc3ncnc(Nc4ccc(OCc5cccc(F)c5)c(Cl)c4)c3c2)cc1
InChIKey: YMNQLBXMJDELBC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR T790M mutant (669 to 1210 residues) expressed in baculovirus expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay
Measurement: IC50 = 66.7 nM (pChEMBL 7.179999828338623)
Descriptors: MW 637.16, ALogP 5.92, HBA 7, HBD 4, PSA 131.26, QED 0.14
Compound (SMILES): CC[C@@H](NC(=O)c1ccc(OC)nc1)[C@H]1CC[C@@H](c2ccnc(OC)c2C(F)F)CC1
InChIKey: VUXXMKIAYMJEHC-RVKKMQEKSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse M109 cells preincubated for 2 hrs followed by recombinant murine IFNgamma stimulation and measured after 18 hrs by fluorescence based microplate reader assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 433.5, ALogP 4.91, HBA 5, HBD 1, PSA 73.34, QED 0.64
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)C1(c2ccc3c(n2)CCN3c2ccccn2)CCC1
InChIKey: BMKIMAJOPUYNPU-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 by human whole blood assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 404.9, ALogP 4.88, HBA 4, HBD 1, PSA 58.12, QED 0.67
Compound (SMILES): CC(C)c1ccc(-c2cc3cc(C(=O)O)c(=O)oc3c3cc(C(=O)O)c(=O)oc23)cc1
InChIKey: AOYPPKYSYHPZRI-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 420.37, ALogP 4.09, HBA 6, HBD 2, PSA 135.02, QED 0.37
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4cccc(F)c4c3=O)C[C@@H]21
InChIKey: WIUCBHWFMJSUTB-PXFYCIBDSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 5 mins in presence of NADPH by LCMS/MS analysis
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 439.92, ALogP 4.59, HBA 4, HBD 1, PSA 63.99, QED 0.63
Compound (SMILES): O=C(NCc1ccncc1)Nc1ccc(S(=O)(=O)N2CCc3ccccc3C2)cc1
InChIKey: BVZCLFOPVBHYDL-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Enzyme Assay and NMN Detection: NAMPT reaction was performed in 50 mM HEPES, pH 7.5, containing 5 mM MgCl2, 0.1% Prionex, 0.005% Tween 20, and 1 mM TCEP at room temperature in Greiner 384-well black polypropylene plates. The concentration of substrates and enzymes in the final assay were as follows: ATP (120 uM), nicotinamide (5 uM), phosphoribosylpyrophosphate (6.25 uM), NAMPT enzyme (16 nM), pyrophosphatase (0.04 U/ml) in the final reaction volume 6 uL. Following 2 h incubation the reaction was stopped by addition 2.5 ul 20% acetophenone in dimethyl sulfoxide (DMSO) and 2.5 ul 2 MKOH. Plates were centrifuges and added with 10.5 ul 88% formic acid. The fluorescence (ex380/em460) was measured following another short incubation and 30 min incubation. The increased concentration of NMN was determined from a calibration curve obtained at the time of experiment.
Measurement: EC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 422.51, ALogP 3.15, HBA 4, HBD 2, PSA 91.4, QED 0.66
Compound (SMILES): O=S(=O)(Oc1ccccc1)n1nc(-c2ccccc2)cc1-c1ccccc1
InChIKey: LKXGPKSQPCFXRN-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 assessed as production of PGE2 using arachidonic acid as a substrate preincubated for 60 mins followed by substrate addition and measured after 2 mins by ELISA analysis
Measurement: IC50 = 9380 nM (pChEMBL 5.03000020980835)
Descriptors: MW 376.44, ALogP 4.39, HBA 5, HBD 0, PSA 61.19, QED 0.52
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cc([C@@H]3OCCc4ccccc43)cs2)C[C@@H]1O
InChIKey: HKKCQZRJLCIYQD-NPDZVAPOSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13564
Assay: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 198 nM (pChEMBL 6.699999809265137)
Descriptors: MW 530.63, ALogP 2.2, HBA 10, HBD 3, PSA 153.73, QED 0.37
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)C(C)(C)NC(=O)CNC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)C(C)C)C(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)NC(C)(C)C(=O)NCC(=O)NCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@H](O)CN(Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(N)=O)C(C)C)C(C)C)C(C)C
InChIKey: KPFGJGYRWXOTFB-MQZFEFAJSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Noncompetitive inhibition of gamma secretase (unknown origin) expressed in HEK293 cells assessed as reduction of A-beta40 levels using varying level of C100-FLAG as substrate incubated for 2 hrs by double reciprocal plot analysis
Measurement: Ki = 1.19 nM (pChEMBL 8.920000076293945)
Descriptors: MW 1865.34
Compound (SMILES): Cn1cc(-c2cc(C(=O)N[C@H]3[C@@H]4COC[C@@H]43)cc(Cc3ccccc3)n2)nn1
InChIKey: AEBQGWUHAHQGBR-YRWFTTLQSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of 6His-Thr-BRD4 (1 to 477 residues) BD2 domain Y390A mutant (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 375.43, ALogP 1.84, HBA 6, HBD 1, PSA 81.93, QED 0.74
Compound (SMILES): COc1ccc2ncc(C#N)c(N3CCC(Cc4nc(C(C)C)no4)CC3)c2c1
InChIKey: OIKGUIRGSMTFAP-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of ABCC1 (unknown origin) expressed in H69AR cells assessed as reduction in daunorubicin accumulation after 180 mins by flow cytometry analysis
Measurement: IC50 = 764 nM (pChEMBL 6.119999885559082)
Descriptors: MW 391.48, ALogP 4.08, HBA 7, HBD 0, PSA 88.07, QED 0.65
Compound (SMILES): Cc1ccc(S(=O)(=O)NCC(C)(C)O)cc1-c1cnc(N)c(-c2cnn(C)n2)n1
InChIKey: MMUWYVIIEWCTLD-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using L-alpha-phosphatidylinositol as substrate incubated for 30 to 60 mins in presence of ATP by Kinase Glo luminescence kinase assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 417.5, ALogP 0.88, HBA 9, HBD 3, PSA 148.91, QED 0.53
Compound (SMILES): Cc1noc(C)c1-c1ccn2c(NC(C)(C)C)c(CCc3ccccc3)nc2c1
InChIKey: GIAKGSNTZVUGML-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 BD1 (unknown origin) using biotinylated-JQ1 peptide as substrate incubated for 1 hr by AlphaScreen assay
Measurement: IC50 = 5630 nM (pChEMBL 5.25)
Descriptors: MW 388.52, ALogP 5.6, HBA 5, HBD 1, PSA 55.36, QED 0.48
Compound (SMILES): COc1cc2c(cc1OC)[C@H](Cc1c[nH]c3c(Cl)cccc13)N(C=O)CC2
InChIKey: FTUNSSCAXJNFIZ-SFHVURJKSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P54750
Assay: Inhibition of recombinant human PDE1A assessed as hydrolysis of [3H]-cAMP measured after 30 mins by Scintillation proximity assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 384.86, ALogP 4.14, HBA 3, HBD 1, PSA 54.56, QED 0.67
Compound (SMILES): Cc1sc(C(=O)c2cncnc2N[C@@H]2C[C@H](COS(N)(=O)=O)[C@@H](O)C2)cc1C1OCCc2ccccc21
InChIKey: SSWIRGSVVTWUMX-DFFAUCTHSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13564
Assay: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 544.66, ALogP 2.51, HBA 10, HBD 3, PSA 153.73, QED 0.36
Compound (SMILES): CC(C)NC(=O)c1cc(-c2ccc(NC(=O)[C@H](O)c3cc(F)cc(F)c3)cc2Cl)cnc1N
InChIKey: JSHFTMAPLMJGCF-HXUWFJFHSA-N
Target: Eukaryotic translation initiation factor 2 subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05198
Assay: Inhibition of eIF2alpha (unknown origin) assessed as eIF2alpha phosphorylation by TR-FRET assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 474.9, ALogP 4.07, HBA 5, HBD 4, PSA 117.34, QED 0.43
Compound (SMILES): CCc1cccc(CC)c1-n1c(CC2CC2)c(C(=O)N2CCNCC2)cc(-c2nc(-c3ccc(Cl)cc3)cs2)c1=O
InChIKey: UIMVBUURSAQZMS-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 5 mins by diaphorase/resazurin-coupled system
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 587.19, ALogP 6.4, HBA 6, HBD 1, PSA 67.23, QED 0.26
Compound (SMILES): Nc1cc(C2CCNCC3(CCCC3)COc3cccc(c3)Cn3cc2cn3)c2nn[nH]c2n1
InChIKey: SKISVGFXKHEGMY-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: MPO Peroxidation Assay (Amplex Red Assay): MPO peroxidation activity was measured in 100 mM KPi (pH 7.4) by utilizing the non-fluorescent reagent Amplex Red (Invitrogen Cat. #A12222) which can be oxidized to the highly fluorescent resorufin. Amplex Red is oxidized by the peroxidase action of MPO to resorufin. Reactions were carried out in 50 μL total volume by adding a 25 μL mixture of 200 pM myeloperoxidase and 40 nM H2O2 (Sigma #349887) to 100 nL inhibitor in 100% DMSO in a 384 well Perkin Elmer Optiplate. Enzyme and compound were preincubated for ten minutes at room temperature.After the ten minute preincubation, 25 μL of an Amplex Red mixture containing 200 μM Amplex Red and 10 mM H2O2 was added to the plate. Kinetic determinations were carried out immediately on a Perkin Elmer Envision (15 minute kinetic read, Ex: 535 nm, Em: 590 nm).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 458.57, ALogP 3.24, HBA 8, HBD 3, PSA 119.56, QED 0.4
Compound (SMILES): Cc1c(NC(=O)Nc2ccccc2S(N)(=O)=O)oc2ccccc12
InChIKey: SORZIMFTAITHNA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 by stopped- flow CO2 hydration assay
Measurement: Ki = 28.2 nM (pChEMBL 7.550000190734863)
Descriptors: MW 345.38, ALogP 3.03, HBA 4, HBD 3, PSA 114.43, QED 0.68
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]ccc4c3N(CCO)C2=O)c1F
InChIKey: CAJWAXHFHVEDLU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 404.37, ALogP 2.8, HBA 5, HBD 2, PSA 90.92, QED 0.68
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: VHRLLJQAIUCUDP-OHMNXDPZSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12392
Assay: Inhibition of rat alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method
Measurement: IC50 = 381 nM (pChEMBL 6.420000076293945)
Descriptors: MW 1625.86
Compound (SMILES): CCc1coc(NC(=O)c2cc3c(nc2OC)nc(C(O)(c2ccccc2)c2ccccc2)n3CC)n1
InChIKey: CNKJHGDZGGLQNR-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into fatty acids by microbeta scintillation counting analysis
Measurement: IC50 = 0.01 nM (pChEMBL 11)
Descriptors: MW 497.56, ALogP 4.55, HBA 8, HBD 2, PSA 115.3, QED 0.32
Compound (SMILES): CCc1cnc(OCC(C)(C)O)c(-c2ccc(S(C)(=O)=O)cc2)c1
InChIKey: BJBKMIXLHYBCCH-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human recombinant COX-1 assessed as reduction in peroxidase activity using arachidonic acid as substrate preincubated for 60 mins followed by substrate addition for 2 secs by ADPH based fluorometric analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 349.45, ALogP 2.86, HBA 5, HBD 1, PSA 76.49, QED 0.87
Compound (SMILES): CC(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)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](CC(=O)O)C(N)=O)[C@@H](C)O
InChIKey: OBHVCHMUTITNOT-XFTXAWHPSA-N
Target: Frizzled-2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q08464
Assay: Antagonist activity at Wnt3a-stimulated rat frizzled-2 expressed in human HEK293superTOP flash cells incubated for 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 2110 nM (pChEMBL 5.679999828338623)
Descriptors: MW 1565.84
Compound (SMILES): O=C(NCCCCN1CCO[C@@H]2c3ccccc3OC[C@H]21)c1ccccc1
InChIKey: CDTGPXQJMIHKOA-TZIWHRDSSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]spiperone from human D3 receptor transfected in HEK293 cell membrane measured after 50 mins by competitive radioligand binding analysis
Measurement: Ki = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 366.46, ALogP 3.03, HBA 4, HBD 1, PSA 50.8, QED 0.8
Compound (SMILES): N#Cc1cccc(-n2cc(-c3n[nH]c4cc(Cl)c(N[C@@H]5CCNC5)cc34)cn2)c1
InChIKey: GLHJKYCHVYCTAN-OAHLLOKOSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Displacement of K5 tracer from Axl (unknown origin) expressed in human HEK293 cells cotransfected with NanoLuc measured after 2 hrs by NanoBRET assay
Measurement: IC50 = 2020 nM (pChEMBL 5.699999809265137)
Descriptors: MW 403.88, ALogP 3.71, HBA 6, HBD 3, PSA 94.35, QED 0.48
Compound (SMILES): COc1ccc(CC[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)[C@@H](C3CCCCC3)c3cc(OC)c(c(OC)c3)OCCCOc3cccc2c3)cc1OC
InChIKey: YSZSLPRWNYBWRS-LSFNHRITSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02790
Assay: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP52 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 715.88, ALogP 7.84, HBA 9, HBD 0, PSA 101.99, QED 0.22
Compound (SMILES): N#Cc1cccc(NC2=C(c3ccccc3Cl)C(=O)NC2=O)c1
InChIKey: VZTOCDZVTNXQRR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O94804
Assay: Binding affinity human STK10 by binding displacement assay
Measurement: Ki = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 323.74, ALogP 2.69, HBA 4, HBD 2, PSA 81.99, QED 0.85
Compound (SMILES): Cc1noc(C)c1-c1ccn2c(NC3CCCCC3)c(CCc3ccccc3)nc2c1
InChIKey: OBPYYXZKNCKVSZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 BD1 (unknown origin) using biotinylated-JQ1 peptide as substrate incubated for 1 hr by AlphaScreen assay
Measurement: IC50 = 7430 nM (pChEMBL 5.130000114440918)
Descriptors: MW 414.55, ALogP 6.14, HBA 5, HBD 1, PSA 55.36, QED 0.41
Compound (SMILES): CCCCC1(c2cc(OC)c3cc(-c4ccccc4)c(=O)oc3c2)CCCC1
InChIKey: KDWHZFMZASEOSD-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in CHO-K1 cell membrane measured after 3 hrs by scintillation spectrometry
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 376.5, ALogP 6.47, HBA 3, HBD 0, PSA 39.44, QED 0.46
Compound (SMILES): COc1cc(-n2cc(CCCCN)nn2)ccc1-c1nc(CCc2ccccc2)cs1.O=C(O)C(F)(F)F
InChIKey: FJPVKQMTPDNAIH-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Inhibition of recombinant His-FLAG-tagged Leishmania infantum TryR dimerization expressed in Escherichia coli BL2(DE3) assessed as reduction in TryR dimer using TS2 as substrate after 16 hrs by ELISA
Measurement: IC50 > 75000 nM (pChEMBL 4.125)
Descriptors: MW 433.58, ALogP 4.47, HBA 7, HBD 1, PSA 78.85, QED 0.37
Compound (SMILES): O=S(=O)(c1ccccc1)n1ccc2c(OCCNCCCCCNc3c4c(nc5ccccc35)CCCC4)cccc21
InChIKey: KNLJKUJSHLRNIN-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine as substrate incubated for 5 mins followed by substrate addition and measured after 5 mins by spectrophotometric based Ellman's method
Measurement: IC50 = 2.17 nM (pChEMBL 8.65999984741211)
Descriptors: MW 582.77, ALogP 6.56, HBA 7, HBD 2, PSA 85.25, QED 0.15
Compound (SMILES): O=C(NO)c1ccccc1Nc1nc(Nc2ccc(N3CCOCC3)cc2)ncc1Cl
InChIKey: CLOCGENGHUXYHT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) measured after 60 mins by ADP-Glo kinase based luminescence assay
Measurement: IC50 = 168.7 nM (pChEMBL 6.769999980926514)
Descriptors: MW 440.89, ALogP 3.57, HBA 8, HBD 4, PSA 111.64, QED 0.34
Compound (SMILES): CCN(CC)c1ccc2c(C)c(CCN3C(=O)NC4(CCN(C(=O)c5ccc[nH]c5=O)C4)C3=O)c(=O)oc2c1
InChIKey: SWEJLKKRPZTJAO-UHFFFAOYSA-N
Target: Immunoglobulin lambda variable 6-57 (SINGLE PROTEIN), Homo sapiens
UniProt: P01721
Assay: Stabilization of AL patient derived full length fluorescein-labeled IGLV6-57 expressed in Escherichia coli BL21 (DE3) measured after 24 hrs by proteolysis coupled-fluorescence polarization assay
Measurement: EC50 = 26003 nM (pChEMBL 4.579999923706055)
Descriptors: MW 533.59, ALogP 2.02, HBA 7, HBD 2, PSA 136.03, QED 0.35
Compound (SMILES): COc1ccc(-c2ccc(S(=O)(=O)N[C@H]3C[C@@H](N=C=S)C3)cc2)cc1F
InChIKey: HMQOATSGVLIACK-GASCZTMLSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition of Test Compounds NAAA Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid, was developed. For three point concentration inhibition assays with hNAAA the following procedure was used. Purified activated NAAA (final concentration of 0.25 μg/mL) was incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples were allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction was allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity was calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 392.48, ALogP 3.41, HBA 5, HBD 1, PSA 67.76, QED 0.6
Compound (SMILES): COc1cnc(Nc2ccc(-c3ccsc3)cn2)nc1Nc1cccc(C(F)(F)F)c1
InChIKey: BZPCXHXAPWYWEV-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human THP-1 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 443.45, ALogP 6.11, HBA 7, HBD 2, PSA 71.96, QED 0.37
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(C)C)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: YYTVUKVXIKXZNG-JBACZVJFSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin)
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 427.64, ALogP 5.1, HBA 6, HBD 2, PSA 66.21, QED 0.64
Compound (SMILES): CCC(=O)N1CC[C@H](Nc2ncnc3c2nc(-c2cnc(C)nc2)n3C)C1
InChIKey: PFVNWFNFIMJELY-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human Ramos cells assessed as reduction in anti-IgM-antibody-induced phosphorylation of AKT at Ser473 residue preincubated for 20 mins followed by anti-IgM antibody stimulation and measured after 30 mins by alphascreen assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 366.43, ALogP 1.55, HBA 8, HBD 1, PSA 101.72, QED 0.75
Compound (SMILES): CCOc1ccc(CCc2nc3cc(-c4c(C)noc4C)ccn3c2NC(C)(C)CC(C)(C)C)cc1
InChIKey: FTXGKSWGXYFJSG-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 BD1 (unknown origin) using biotinylated-JQ1 peptide as substrate incubated for 1 hr by AlphaScreen assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 488.68, ALogP 7.42, HBA 6, HBD 1, PSA 64.59, QED 0.27
Compound (SMILES): CC(Sc1nc2c(cnn2C)c(=O)n1-c1ccccc1)c1ccccc1
InChIKey: JNPNRKXZLIGUCT-UHFFFAOYSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 362.46, ALogP 3.97, HBA 6, HBD 0, PSA 52.71, QED 0.41
Compound (SMILES): CC(C)C(C(=O)NC(CO)CO)c1ccc(-c2ccc3cccc(F)c3c2)[nH]c1=O
InChIKey: AVVXVDVIYIOPQS-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor expressed in CHO cells by cell based cAMP functional assay
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 412.46, ALogP 2.54, HBA 4, HBD 4, PSA 102.42, QED 0.48
Compound (SMILES): CC(C)Oc1nc(OCC(C)(C)O)c(-c2ccc(S(C)(=O)=O)cc2)cc1CO
InChIKey: WNRSHKBWGXMBIJ-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human recombinant COX-1 assessed as reduction in peroxidase activity using arachidonic acid as substrate preincubated for 60 mins followed by substrate addition for 2 secs by ADPH based fluorometric analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 409.5, ALogP 2.58, HBA 7, HBD 2, PSA 105.95, QED 0.69
Compound (SMILES): N#Cc1cncc(COc2cc(OC3CCc4c(-c5ccccc5)cccc43)c(Cl)cc2CN[C@@H](CO)C(=O)O)c1
InChIKey: XFMADIVPJSLSMQ-XLTVJXRZSA-N
Target: Programmed cell death 1 ligand 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZQ7
Assay: Enzyme-Linked Immunosorbent AssayâELISA: Plates were coated with 1 Î¼g/mL of human PD-L1 (obtained from R&D) in PBS overnight at 4Â° C. The wells were then blocked with PBS containing 2% BSA in PBS (W/V) with 0.05% TWEEN-20 for 1 hour at 37Â° C. The plates were washed 3 times with PBS/0.05% TWEEN-20 and the samples were diluted to 1:5 in dilution medium in the ELISA plates. Human PD-1 and biotin 0.3 Î¼g/mL (ACRO Biosystems) were added and incubated for 1 hour at 37Â° C. then washed 3 times with PBS/0.05% TWEEN-20. A second block was added with PBS containing 2% BSA in PBS (W/V)/0.05% TWEEN-20 for 10 min at 37Â° C. and was washed 3 times with PBS/0.05% TWEEN-20. Streptavidin-HRP was added for 1 hour at 37Â° C. then washed 3 times with PBS/0.05% TWEEN-20. TMB substrate was added and reacted for 20 min at 37Â° C. A stop solution (2 N aqueous H2SO4) was added. The absorbance was read at 450 nm using a micro-plate spectrophotometer.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 570.05, ALogP 5.45, HBA 7, HBD 3, PSA 124.7, QED 0.22
Compound (SMILES): Cc1ccc(-n2nc(CCC(=O)O)cc2-c2cc(Cl)cc(Cl)c2)cc1
InChIKey: NFHUNGNFEGORNW-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P28702
Assay: Agonist activity at human RXRbeta transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 375.26, ALogP 5.17, HBA 3, HBD 1, PSA 55.12, QED 0.67