lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-c2c(C)nc3c(N4CC[C@@H](NC(=O)c5ccccc5)C4)cc(C)nn23)cc1OC
InChIKey: MDEXPLFSJLTLJE-OAQYLSRUSA-N
Target: Sphingomyelin phosphodiesterase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY59
Assay: Fluorescence Based Assay: The fluorescence based assay to monitor the activity of human nSMase2 in the presence or absence of potential inhibitors has been described recently. Figuera-Losada, et al. Lysate of cells expressing recombinant nSMase2 is used to catalyze the hydrolysis of sphingomyelin (SM) to ceramide and phosphorylcholine. Phosphorylcholine undergoes dephosphorylation in a reaction catalyzed by alkaline phosphatase (4 U/mL) to produce choline which in turn is oxidized by choline oxidase (0.1 U/mL) to betaine and hydrogen peroxide (H2O2). Hydrogen peroxide is made to react with Amplex red (50 μM) in the presence of horseradish peroxidase (HRP, 1 U/mL) to generate the fluorescent molecule resorufin. Generation of fluorescence is monitored by measuring relative florescence units (RFU) with excitation at 530 nm and emission at 590 nm. Extent of fluorescence is directly proportional to the extent of SM hydrolysis. Substrate stock solution is prepared in 2% Triton X-100 and sonicated for 1 min. Reactions are carried out for 1 h at 37° C. in 100 mM Tris-HCl pH 7.4, 10 mM MgCl2, 0.2% Triton X-100. This assay has been optimized in 384-well format (50 μL total volume per well) under conditions where nSMase2-catalyzed hydrolysis of SM is linear with respect to nSMase2 concentration, time of incubation and SM concentration (FIGS. 3A-3C). The assay has high reliability (Z′=0.8-0.9). It is used for compound screening, IC50 determinations and mode of inhibition studies
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 471.56, ALogP 4.04, HBA 7, HBD 1, PSA 80.99, QED 0.46
Compound (SMILES): C[N+]12CCC(c3ccc(-c4cc(C(=O)O)cc5cc(-c6ccc(C(F)(F)F)cc6)ccc45)cc3)(CC1)CC2
InChIKey: LTEDSKLEEXLKDM-UHFFFAOYSA-O
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15391
Assay: Inhibition of MRS4174 binding to human P2Y14R expressed in CHO cells pre-incubated for 30 mins before MRS4174 addition and further incubated for 30 mins at pH 7.4 by flow cytomtery based competitive fluorescence assay
Measurement: IC50 = 38.3 nM (pChEMBL 7.420000076293945)
Descriptors: MW 516.58, ALogP 7.77, HBA 1, HBD 1, PSA 37.3, QED 0.28
Compound (SMILES): OC(CN1CCC2(CCN(CCSC(c3ccc(F)cc3)c3ccc(F)cc3)CC2)C1)c1ccccc1
InChIKey: KCDKRLPOCAPTCW-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from SERT in Sprague-Dawley rat midbrain membranes incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 522.71, ALogP 6.31, HBA 4, HBD 1, PSA 26.71, QED 0.36
Compound (SMILES): CNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccc(-c5ccc(F)cc5)cc4F)cccn23)cn1.Cl
InChIKey: LKXRSVMSDSUZLY-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human recombinant CYP1A2 assessed as reduction in metabolite formation using CEC as substrate incubated for 20 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 484.51, ALogP 5.59, HBA 5, HBD 1, PSA 68.52, QED 0.34
Compound (SMILES): CONC(=O)[C@H]1CC=C(CCC=C(C)C)C[C@@H]1c1ccccc1
InChIKey: HBECBMVZZAFGQI-RBUKOAKNSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki = 16600 nM (pChEMBL 4.78000020980835)
Descriptors: MW 313.44, ALogP 4.53, HBA 2, HBD 1, PSA 38.33, QED 0.62
Compound (SMILES): CSc1nc2ccccc2n1-c1csc(NCC(=O)c2ccc(Cl)cc2)n1
InChIKey: ZUBVNAVETYHORI-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by EIA
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 414.94, ALogP 5.15, HBA 7, HBD 1, PSA 59.81, QED 0.35
Compound (SMILES): CCCCCC(=O)N[C@H](C(=O)NCc1ccc(CN)cc1)c1ccc(OCc2ccccc2)cc1.O=C(O)C(F)(F)F
InChIKey: DGULCRVBNXUFMQ-JCOPYZAKSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of Dengue virus serotype 2 NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Nle-Lys-Arg-Arg-Ser-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition and measured for 15 mins by FRET assay
Measurement: Ki = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 473.62, ALogP 4.78, HBA 4, HBD 3, PSA 93.45, QED 0.31
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2ccccc2Br)cc(OC)c1OC
InChIKey: AADMHMQHAHPDLZ-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 546.46, ALogP 4.23, HBA 6, HBD 2, PSA 89.13, QED 0.52
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCc2ccccc2)CC(=O)NC2CCC2)nn1CC(C)C
InChIKey: NCXHRJGXCGCKIB-DEOSSOPVSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHOK1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 3110 nM (pChEMBL 5.510000228881836)
Descriptors: MW 532.69, ALogP 5.01, HBA 6, HBD 2, PSA 94.48, QED 0.32
Compound (SMILES): CCCCCC(O)/C=C/c1c(Cl)cc(Cl)c(=O)n1CCc1ccc(C(=O)O)cc1
InChIKey: VJOKJQWLVBLRPZ-ZHACJKMWSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Agonist activity at human EP4 receptor expressed in HEK293 cells by calcium-5 dye based FLIPR assay
Measurement: EC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 438.35, ALogP 5.05, HBA 4, HBD 2, PSA 79.53, QED 0.51
Compound (SMILES): Cc1nn(CCO)cc1CN(C)Cc1csc(-c2ccccc2)n1
InChIKey: YOOUCGLWTXTEGZ-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-DTG from recombinant sigma 2 receptor (unknown origin) expressed in baculovirus infected Sf9 cell membranes after 1.5 hrs by scintillation counting analysis
Measurement: Ki = 2373 nM (pChEMBL 5.619999885559082)
Descriptors: MW 342.47, ALogP 2.94, HBA 6, HBD 1, PSA 54.18, QED 0.72
Compound (SMILES): CCCCCc1cc(OCC)cc(OCCCCCCCCCCC(=O)NC2CC2)c1
InChIKey: IIUUSRKKXMTJCI-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 431.66, ALogP 6.99, HBA 3, HBD 1, PSA 47.56, QED 0.24
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(CN3CCN(C(=O)CCCc4cn(CCOCCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)nn4)CC3)c(C(F)(F)F)c2)cc1C#Cc1cnc2cccnn12
InChIKey: SVYYVGZMWJYFIE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of human LYN using poly(Glu,Tyr)4:1 substrate and [gamma-33P]-ATP incubated for 40 mins by scintillation counting method
Measurement: IC50 = 44.2 nM (pChEMBL 7.360000133514404)
Descriptors: MW 1087.13
Compound (SMILES): O=c1n(CCCCN2CCN(c3cccc4sccc34)CC2)nc2c(Br)cccn12
InChIKey: SUPQFIADWRBCSZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 486.44, ALogP 4.08, HBA 7, HBD 0, PSA 45.78, QED 0.39
Compound (SMILES): O=C(N[C@@H]1CCCc2c1cnn2-c1ccccc1F)c1ncc2ccccn12
InChIKey: KCSUDDCZEAJVHR-QGZVFWFLSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition Assay: Assay B: Example compounds as described herein were dispensed with an acoustic liquid handler, Echo 550 (Labcyte) to a maximum volume of 50 nl per well in a 384 well plate. DHODH enzyme assays were performed with 4 nM recombinant human DHODH (purified essentially as described by Walse et. al., Biochemistry, 47, 8929-8936 (2008)). The reaction mixture consisted of 2 mM DL-dihydroorotic acid (#D7003, Sigma-Aldrich), 100 μM 3,4-dimethoxy-5-methyl-p-benzoquinone (#D9150, Sigma-Aldrich), and 200 μM 2,6-dichlorophenolindophenol sodium salt (DCIP) (#D1878, Sigma-Aldrich) in enzyme buffer (50 mM Tris-HCl pH 8.0, 0.1% Triton X-100, 150 mM KCl) in a final volume of 50 μl per well. A stock solution of 80 mM DCIP was prepared in DMSO just before use. Loss in absorbance by chromogen DCIP was measured at 595 nm at RT every 2 min for an hour with a plate reader (Envision, Perkin Elmer).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 375.41, ALogP 3.47, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): O=C(O)c1cccc(-c2ccc(C3(C(=O)Nc4ccc(C(=O)NO)cc4)CCCC3)cc2)c1
InChIKey: LXUDZYCOGQLEHS-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human recombinant HDAC2 pre-incubated for 30 mins before Ac-Leu- Gly-Lys(Ac)-AMC substrate addition and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 444.49, ALogP 4.62, HBA 4, HBD 4, PSA 115.73, QED 0.33
Compound (SMILES): COc1ccc2nc(NC(=O)c3ccc(C(=O)c4cccnc4)cc3)sc2c1
InChIKey: SVNXVLSQFKQHSG-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 389.44, ALogP 4.18, HBA 6, HBD 1, PSA 81.18, QED 0.52
Compound (SMILES): C[n+]1cn([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)NCCc3c[nH]c4ccccc34)[C@@H](O)[C@H]2O)c2nc(N)nc([O-])c21.N.N
InChIKey: WGJXDDFPUZREMR-BQTMTNBUSA-N
Target: m7GpppX diphosphatase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96C86
Assay: Inhibition of human DcpS using pyrene labeled 7-methylguanosine triphosphate as substrate preincubated for 15 mins followed by enzyme addition by fluorescence assay
Measurement: Ki = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 599.43, ALogP -0.92, HBA 12, HBD 7, PSA 254.24, QED 0.09
Compound (SMILES): COc1c(S(C)(=O)=O)ccc(O[C@@H](C)C(F)(F)F)c1C(=O)N1CC(c2ncc(C(F)(F)F)cc2Cl)C1
InChIKey: LTZZDIGOHHZSSD-JTQLQIEISA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48067
Assay: Inhibition of human GlyT1 expressed in human HEK cells assessed as reduction in radiolabeled glycine uptake by scintillation proximity assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 560.9, ALogP 4.74, HBA 6, HBD 0, PSA 85.8, QED 0.47
Compound (SMILES): CC(C)CN[C@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: PPMCDHOGVXMNOY-YADHBBJMSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 439.6, ALogP 3.08, HBA 5, HBD 3, PSA 100.35, QED 0.56
Compound (SMILES): O=C(N[C@H]1CN(S(=O)(=O)c2ccccc2)C[C@@H]1C(=O)N[C@H]1CCCNC1)c1cc(-c2ccccc2)on1
InChIKey: KEHIQDJENNRLHR-RRPUWOKSSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 4.79 nM (pChEMBL 8.319999694824219)
Descriptors: MW 523.62, ALogP 1.63, HBA 7, HBD 3, PSA 133.64, QED 0.43
Compound (SMILES): Cc1nn([C@H](C)c2ccc(Cl)cc2Cl)c2nc(N3CC([C@H]4CCCN(CCC(N)=O)C4)C3)cnc12
InChIKey: FATSWIDSLHDFRU-SJORKVTESA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: Antagonist activity at CCR4 in human CCRF-CEM cells assessed as inhibition of CCL22-mediated chemotaxis preincubated for 30 mins followed by CCL22 addition and measured after 60 mins in presence of 100% human serum by CellTiter-Glo assay
Measurement: IC50 = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 516.48, ALogP 4.07, HBA 7, HBD 1, PSA 93.17, QED 0.51
Compound (SMILES): N#CC1(C(=O)N2CC=C(c3cccc4nc(NC(=O)C5CC5)nn34)CC2)CC1
InChIKey: IMVMEMWELLQQQP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) in presence of ATP at Km concentration by caliper assay
Measurement: IC50 = 441 nM (pChEMBL 6.360000133514404)
Descriptors: MW 376.42, ALogP 2, HBA 6, HBD 1, PSA 103.39, QED 0.88
Compound (SMILES): CC(C)=CCC[C@H](C)[C@@H]1C=C[C@]2(C(=O)O)[C@@H](CC(C)=C[C@H]2/C=C(\C)[C@H]2CC[C@H](C(=O)O)CC2)C1
InChIKey: OTBMTWUPWVANPM-BNAFIAHISA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 468.68, ALogP 7.44, HBA 2, HBD 2, PSA 74.6, QED 0.36
Compound (SMILES): Nc1cc(-c2cn(-c3ccccc3)c3cnccc23)ccn1
InChIKey: NOAYWSNRHLCNJQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human His/GST-tagged GSK3beta (2 to 433 residues) expressed in baculovirus infected Sf9 cells using Ulight-glycogen synthase peptide as substrate incubated for 30 mins by TR-FRET LANCE method
Measurement: IC50 = 1950 nM (pChEMBL 5.710000038146973)
Descriptors: MW 286.34, ALogP 3.67, HBA 4, HBD 1, PSA 56.73, QED 0.61
Compound (SMILES): NC(=O)c1cccc2[nH]c(-c3cncnc3)nc12
InChIKey: KGPVLUASGQKUHA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16513
Assay: Displacement of tracer from PKN2 (unknown origin) by TR-FRET assay
Measurement: Ki = 23830 nM (pChEMBL 4.619999885559082)
Descriptors: MW 239.24, ALogP 1.12, HBA 4, HBD 2, PSA 97.55, QED 0.7
Compound (SMILES): B.CP(c1ccccc1)c1ccc(O)cc1
InChIKey: CVXWCCHYGCGDJZ-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at human Gal4-fused ERbeta expressed in HEK293 cells assessed as inhibition of E2-induced transcriptional activation after 24 hrs by luciferase/beta-galactosidase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 230.06
Compound (SMILES): Cc1ccccc1Nc1nc(Nc2ccncc2)ncc1Cl
InChIKey: SNCUFQOXMSHUEF-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 311.78, ALogP 4.32, HBA 5, HBD 2, PSA 62.73, QED 0.75
Compound (SMILES): C=C1CC(CBr)(c2ccc(F)cc2)OC1=O
InChIKey: NFMNEASECHTBTP-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin)
Measurement: IC50 = 64000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 285.11, ALogP 2.92, HBA 2, HBD 0, PSA 26.3, QED 0.47
Compound (SMILES): COc1cc(/C=C/C(=O)O)ccc1OCc1cn(-c2cccc(C)c2)nn1
InChIKey: HUORZFJKAJHQHU-VQHVLOKHSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 using p-nitrophenyl acetate as substrate by UV-VIS spectrophotometric analysis
Measurement: IC50 = 5240 nM (pChEMBL 5.28000020980835)
Descriptors: MW 365.39, ALogP 3.26, HBA 6, HBD 1, PSA 86.47, QED 0.65
Compound (SMILES): c1cn2cc(-c3ccc4c(n3)NCCO4)nc(Nc3ccc(N4CCN(C5COC5)CC4)cc3)c2n1
InChIKey: MRFQCDAPJIZXOH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay
Measurement: EC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 484.56, ALogP 2.86, HBA 10, HBD 2, PSA 92.08, QED 0.44
Compound (SMILES): CC(=O)c1ccc(NC(=O)CS)cc1
InChIKey: WBJOQROPHCHERE-UHFFFAOYSA-N
Target: Collagenase ColH (SINGLE PROTEIN), Hathewaya histolytica
UniProt: Q46085
Assay: Inhibition of Clostridium histolyticum ColH peptidase domain expressed in Escherichia coli BL21(DE3) cells using Mca-Ala-Gly-Pro-Pro-Gly-Pro-Dpa-Gly-Arg-NH2 as substrate preincubated for 1 hr followed by substrate addition measured for 2 mins by FRET assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 209.27, ALogP 1.76, HBA 3, HBD 2, PSA 46.17, QED 0.59
Compound (SMILES): COc1cc2c(cc1O)C(c1c(Cl)cccc1Cl)CNCC2
InChIKey: ITPDHEQZMNITSW-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from dopamine D5 receptor (unknown origin)
Measurement: Ki = 25.4 nM (pChEMBL 7.590000152587891)
Descriptors: MW 338.23, ALogP 3.99, HBA 3, HBD 2, PSA 41.49, QED 0.87
Compound (SMILES): CCC[C@H](C)Oc1nc(N)c2[nH]c(=O)n(CC3CCN(CCO)CC3)c2n1.Cl
InChIKey: ZGOALCVOHPKQSO-YDALLXLXSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 expressed in HEK293 cells assessed as induction of NFKappaB activity after 24 hrs by SEAP reporter gene assay
Measurement: EC50 = 4060 nM (pChEMBL 5.389999866485596)
Descriptors: MW 378.48, ALogP 0.97, HBA 8, HBD 3, PSA 122.29, QED 0.63
Compound (SMILES): Cc1ccc(-c2cc(C(F)(F)F)ccc2[C@H]2CCOc3cc(S(=O)(=O)Nc4ccncn4)ccc32)cn1
InChIKey: OVCBYEXPONMHTH-OAQYLSRUSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay
Measurement: IC50 = 1103 nM (pChEMBL 5.960000038146973)
Descriptors: MW 526.54, ALogP 5.58, HBA 6, HBD 1, PSA 94.07, QED 0.36
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CN(S(=O)(=O)c4ccccc4)C[C@@H]3C(=O)N[C@@H]3CCCN(C)C3)cc2c1
InChIKey: QPXGPLCMDWOSJQ-KJWPAHLWSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 0.274 nM (pChEMBL 9.5600004196167)
Descriptors: MW 523.66, ALogP 2.11, HBA 5, HBD 3, PSA 114.61, QED 0.46
Compound (SMILES): Nc1nccc2cc(CNC(=O)[C@@H]3CCCN3C(=O)[C@@H](CC3CCCCC3)NC3CCCCC3)ccc12
InChIKey: CJPQDOALKKFQAR-SXOMAYOGSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 505.71, ALogP 4.69, HBA 5, HBD 3, PSA 100.35, QED 0.48
Compound (SMILES): Cc1cnc(-c2ccc(-c3ccco3)cc2)n1Cc1ccccc1OCCCCCC(=O)O
InChIKey: PZVNGYWXLMIOJJ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Modulator activity at GAL4-fused human PPARalpha LBD (unknown origin) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay
Measurement: EC50 = 6970 nM (pChEMBL 5.159999847412109)
Descriptors: MW 444.53, ALogP 6.19, HBA 5, HBD 1, PSA 77.49, QED 0.28
Compound (SMILES): Cc1ccc(Nc2nc(Nc3ccc(N4CCN(C)CC4)cn3)ncc2Cl)cc1
InChIKey: QTIXYWRLCYOCRY-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 = 1450 nM (pChEMBL 5.840000152587891)
Descriptors: MW 409.93, ALogP 4.07, HBA 7, HBD 2, PSA 69.21, QED 0.66
Compound (SMILES): COc1cccc(-c2ccc(COC3CN(C#N)C3)c(C(F)(F)F)c2)c1
InChIKey: DGRUGCJTCBRXGN-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition 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, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is 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 are 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 is 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 is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 362.35, ALogP 4.06, HBA 4, HBD 0, PSA 45.49, QED 0.75
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CCCC[C@H]3C)c12
InChIKey: ISZNDMVFJQJILW-SCZZXKLOSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 245.33, ALogP 2.85, HBA 2, HBD 2, PSA 61.54, QED 0.81
Compound (SMILES): COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)C(C)(C)C
InChIKey: LPGGYDYQUYLLOU-LGDXJAAOSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-106 cells using EDANS/DABCYL-labelled 10-amino acid containing protease cleavage site as substrate preincubated for 1 hr followed by substrate addition and measured for 60 mins by FRET assay
Measurement: Ki = 0.372 nM (pChEMBL 9.430000305175781)
Descriptors: MW 611.74, ALogP 3.33, HBA 8, HBD 4, PSA 144.45, QED 0.29
Compound (SMILES): CCN(c1ccc(C(=O)NO)cc1)S(=O)(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
InChIKey: NTZJQYISEKJEPR-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of C-terminal FLAG-tagged full length human HDAC6 expressed in baculovirus expression system using FAM-RHKK(Ac)-NH2 substrate incubated for 5 hrs by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.36, ALogP 4.06, HBA 4, HBD 2, PSA 86.71, QED 0.4
Compound (SMILES): O=C(Nc1ccccc1-c1cc(F)c(F)c(F)c1)OCC1CCNCC1
InChIKey: BSNRCPZANSBCBD-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 364.37, ALogP 4.32, HBA 3, HBD 2, PSA 50.36, QED 0.79
Compound (SMILES): Cc1ccc(-c2ccc(COC3CN(C#N)C3)cc2)cc1
InChIKey: ZFVIUFGPJQNLIT-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition 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, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is 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 are 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 is 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 is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 278.36, ALogP 3.34, HBA 3, HBD 0, PSA 36.26, QED 0.8
Compound (SMILES): C=CC(=O)N1CC[C@H](Nc2ccc(C(N)=O)c3[nH]c(C)c(C)c23)C1
InChIKey: RCXJYPLURGYACL-LBPRGKRZSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human Ramos B cells assessed as reduction in BCR-stimulated calcium flux after 1 hr in dark condition measured for 180 sec
Measurement: IC50 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 326.4, ALogP 2.08, HBA 3, HBD 3, PSA 91.22, QED 0.75
Compound (SMILES): Cc1cc(Cl)cc(-c2ccnc3cc(CN4C(=O)CCC4=O)sc23)c1O[C@H]1C[C@H](N)C1
InChIKey: RWJHYKMAOUYNOE-SHTZXODSSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of USP7 in human RKO cells transfected with p53 luciferase reporter vector assessed as increase in p53-dependent luciferase activity measured after 18 hrs by BrightGlo luciferase assay
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 455.97, ALogP 4.44, HBA 6, HBD 1, PSA 85.52, QED 0.57
Compound (SMILES): COCCOc1nc(N)c2nc(O)n(Cc3ccc(C(=O)N[C@H]4C(O)O[C@H](CO)[C@@H](O)[C@@H]4O)cc3)c2n1
InChIKey: OOAZSJXRAFBSOK-GIQHGULNSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: P58681
Assay: Agonist activity at TLR7 in mouse BMDC cells assessed as immunostimulatory activity by measuring increase in IL6 secretion incubated for 18 hrs by ELISA
Measurement: EC50 = 239 nM (pChEMBL 6.619999885559082)
Descriptors: MW 520.5, ALogP -2.28, HBA 14, HBD 7, PSA 227.56, QED 0.15
Compound (SMILES): Cn1cc(-c2ncc(C#N)c(N3CCN(c4cccc(F)c4)C(C)(C)C3)n2)cn1
InChIKey: LHBOCJIOQYAOLR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: This assay was developed and further optimized from a kit produced by Upstate (Millipore catalog #33-047) (Millipore Sigma, Billerica Mass., USA) and has been configured for high throughput screening (HTS) and structure-activity relationship (SAR) screening. Briefly, this procedure exploits the exquisite specificity and high affinity binding of enzyme reaction substrate phosphatidyl(3,4,5)triphosphate (PIP3) to the GRP1 pleckstrin homology (PH) domain to generate the signal. In the absence of PIP3, an HTRF (Homogeneous Time-Resolved Fluorescence energy transfer) complex is formed consisting of europium (u)-labeled anti-GST, GST tagged GRP1-PH domain, biotin-PIP3 (biotinylated-PIP3) and streptavidin conjugated APC (Allophycocyanin). The native PIP3 produced by PI3-Kinase activity disrupts in a competitive manner the biotin-PIP3 from the pleckstrin homology (PH) domain, resulting in the loss of energy transfer (HTRF complex) and a decrease in the signal. The format of this assay is the same for all 4 isoforms of PI3K; the differences lie in the concentration of enzyme used to achieve robust assay window. The alpha, beta, and delta assays are run at 0.5, 1, and 0.3 nM enzymes and the gamma assay is run at 5 nM enzyme. The ATP concentration is 100 uM in the alpha, beta, and delta assays and 50 uM adenosine triphosphate (ATP) in the gamma assay. All reactions are run at 5 uM PIP2.
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 391.45, ALogP 2.99, HBA 7, HBD 0, PSA 73.87, QED 0.68
Compound (SMILES): O=C(N[C@H]1CN(S(=O)(=O)c2ccccc2)C[C@@H]1C(=O)N[C@H]1CCCNC1)c1cc(C2CC2)n[nH]1
InChIKey: JJDCKCHTXMUVKM-MDKPJZGXSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 687 nM (pChEMBL 6.159999847412109)
Descriptors: MW 486.6, ALogP 0.57, HBA 6, HBD 4, PSA 136.29, QED 0.45
Compound (SMILES): O=C(O)C(=O)O.c1ccc(CC2CCN(C[C@H]3CS[C@]4(CCc5ccccc54)S3)CC2)cc1
InChIKey: BVVOROYVDXNGFU-ROOQTRKKSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-ditolylguanidine from human Sigma 2 receptor by radioligand displacement assay
Measurement: Ki = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 395.64, ALogP 5.59, HBA 3, HBD 0, PSA 3.24, QED 0.66
Compound (SMILES): O=C(c1cc(Br)c(O)c(Br)c1)N1CCOc2ccncc21
InChIKey: ZMVGQIIOXCGAFV-UHFFFAOYSA-N
Target: Solute carrier family 22 member 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q4U2R8
Assay: Inhibition of human OAT1
Measurement: Ki = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 414.05, ALogP 3.35, HBA 4, HBD 1, PSA 62.66, QED 0.78
Compound (SMILES): COc1cc2c3c(c1OC)-c1cc(NS(C)(=O)=O)ccc1CC3N(C)CC2
InChIKey: VVJISIDSYVEBMB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5-HT7A receptor expresssed in stable HEK cell membrane incubated for 90 mins by microbeta counting method
Measurement: Ki = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 388.49, ALogP 2.83, HBA 5, HBD 1, PSA 67.87, QED 0.87
Compound (SMILES): c1cc(-c2cn(C3CCOCC3)c3cnccc23)ccn1
InChIKey: NUTLDYDKKRBTHZ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human His/GST-tagged GSK3beta (2 to 433 residues) expressed in baculovirus infected Sf9 cells using Ulight-glycogen synthase peptide as substrate incubated for 30 mins by TR-FRET LANCE method
Measurement: IC50 = 44480 nM (pChEMBL 4.349999904632568)
Descriptors: MW 279.34, ALogP 3.45, HBA 4, HBD 0, PSA 39.94, QED 0.72
Compound (SMILES): COc1ccc(-c2cnn3c(N)c(-c4ccccc4)c(OC4CCN(C)CC4)nc23)cc1OC
InChIKey: YZNIHXUBUWEUCM-UHFFFAOYSA-N
Target: Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of KIF5B-RET V804M mutant (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 459.55, ALogP 4.14, HBA 8, HBD 1, PSA 87.14, QED 0.46
Compound (SMILES): COc1cc(C2C3=C(CCCC3=O)NC3=C2C(=O)CCC3)ccc1OCc1ccc(F)cc1
InChIKey: VXFZTYCXOSXQLQ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine BuchE using butyrylthiocholine as substrate by Ellman's method
Measurement: IC50 = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 447.51, ALogP 5.11, HBA 5, HBD 1, PSA 64.63, QED 0.69
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CCN(S(=O)(=O)c4cccnc4)C[C@@H]3C(=O)NCCN(C)C)cc2c1
InChIKey: GNKOEDGFOSONTA-UNMCSNQZSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [His[125I]]-ghrelin from GHS-R1a (unknown origin) expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: IC50 = 17.5 nM (pChEMBL 7.760000228881836)
Descriptors: MW 512.64, ALogP 1.36, HBA 6, HBD 3, PSA 127.5, QED 0.42
Compound (SMILES): Cc1ccc2c(c1)C(=O)N1CCCC[C@H]1c1cc3nc(N4CC[C@H](N)C4)cc(n3n1)N(C)CCCCO2
InChIKey: RNKULGCYSCGYOZ-REWPJTCUSA-N
Target: Fusion glycoprotein F0 (SINGLE PROTEIN), Human respiratory syncytial virus A (strain A2)
UniProt: P03420
Assay: Inhibition of Human respiratory syncytial virus Fusion protein D486N mutant expressed in Hep2 cells assessed as reduction in virus-induced cytopathic effect after 4 days by XTT assay
Measurement: EC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 503.65, ALogP 3.55, HBA 8, HBD 1, PSA 92.23, QED 0.54
Compound (SMILES): COC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(-n2c(C)ccc2CN(C)C)cc1)c1ccccc1
InChIKey: JKLIAVHZXLNJPF-ZIADKAODSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of N-terminal GST-fused human PDGFRbeta cytoplasmic domain (557 to 1106 (end) residues) expressed in baculovirus expression system using FAM-labeled peptide and ATP as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by mobility shift assay
Measurement: IC50 = 45.3 nM (pChEMBL 7.340000152587891)
Descriptors: MW 506.61, ALogP 5.57, HBA 6, HBD 2, PSA 75.6, QED 0.25
Compound (SMILES): O=C(O)CCCCC(=O)N1CCc2c(n(Cc3cccc(F)c3)c3ncccc23)C1
InChIKey: DJNNANGRROWQRL-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition Assay: 10 μL of a test compound solution (10% dimethyl sulfoxide) at each concentration and 40 μL of a 5 μg/mL human ENPP2 solution (buffer A: 100 mmol/L Tris-HCl (pH 9.0), 500 mmol/L NaCl, 5 mmol/L MgCl2, 0.05% Triton X-100) were mixed, 50 μL of a 2 mmol/L 16:0-lysophosphatidylcholine (LPC) solution (buffer A) was further added to react at 37° C. for 24 hours. Subsequently, to 10 μL of the reaction solution was added 90 μL of a measurement buffer (0.5 mmol/L aminoantipyrine, 0.3 mmol/L N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3-methylaniline, 1 U/mL peroxidase, 3 U/mL choline oxidase, 100 mmol/L Tris-HCl (pH 8.5), 5 mmol/L CaCl2) to react at 37° C. for 20 minutes, and spectrophotometric determination was performed at 555 nm.Using a standard curve, a choline production amount (enzyme activity) in each test compound was calculated, and the inhibitory activity rate of each test compound was calculated, wherein the enzyme activity in a positive control to which a test compound is not added, was a 0% inhibition rate, and the enzyme activity in a negative control to which a test compound and human ENPP2 are not added, were 100% inhibition.
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 409.46, ALogP 3.75, HBA 4, HBD 1, PSA 75.43, QED 0.6
Compound (SMILES): CC(=O)c1ccc2c(c1)c1cc(C(C)=O)ccc1n2CCNC(C)C
InChIKey: JKCSODVERGVDLT-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 3A (SINGLE PROTEIN), Mus musculus
UniProt: O88508
Assay: Inhibition of murine DNMT3A catalytic domain-mediated DNA methylation using 5'-6FAM-tagged 30-mer duplex DNA (22 AT bp) as substrate preincubated for 30 mins followed by enzyme addition
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 336.44, ALogP 4.2, HBA 4, HBD 1, PSA 51.1, QED 0.69
Compound (SMILES): CCCCCC(O)CCc1c(Cl)cc(Cl)c(=O)n1CCc1ccc(C(=O)O)cc1
InChIKey: ALCYGSHSWNBKSO-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP1 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P34995
Assay: Agonist activity at human EP1 receptor expressed in HEK293 cells by calcium-5 dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.37, ALogP 4.97, HBA 4, HBD 2, PSA 79.53, QED 0.48
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc(B(O)O)cc3)ncc2C(F)(F)F)c1
InChIKey: LMWZRTIJZLQQJP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human His-tagged full length BTK expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 443.19
Compound (SMILES): COC(=O)CN(C)C(=O)[C@H](CCc1ccccc1)NC(=O)c1cc(-c2c(OC)cccc2OC)n(CC(C)C)n1
InChIKey: NDCHJRYZZHZGFB-QFIPXVFZSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 266 nM (pChEMBL 6.579999923706055)
Descriptors: MW 550.66, ALogP 3.59, HBA 8, HBD 1, PSA 111.99, QED 0.32
Compound (SMILES): CCCCCC(=O)N[C@H](C(=O)Nc1ccc2[nH]ncc2c1)c1ccc(OCc2ccccc2)cc1
InChIKey: HOGOYGDPWYKOBC-MHZLTWQESA-N
Target: NS3 (SINGLE PROTEIN), West Nile virus
UniProt: K4FQI5
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets West Nile NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on West Nile virus (strain NY-99) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 470.57, ALogP 5.52, HBA 4, HBD 3, PSA 96.11, QED 0.25
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2ccccc2C)cc(OC)c1OC
InChIKey: GCSXWQQSFNSSSR-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 481.59, ALogP 3.77, HBA 6, HBD 2, PSA 89.13, QED 0.6
Compound (SMILES): CCCCn1c(=O)c(C(=O)NC23CC4CC(CC(C4)C2)C3)c(O)c2nn(C)cc21
InChIKey: VKGNECHCJCUDGH-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at recombinant human CB2R expressed in CHOK1 cells assessed as increase in NKH477-stimulated intracellular cAMP levels after 30 mins by chemiluminescent based cAMP Hunter assay
Measurement: EC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 398.51, ALogP 2.94, HBA 6, HBD 2, PSA 89.15, QED 0.81
Compound (SMILES): O=C(Nc1ccc(-c2nc3ccc(Br)cc3[nH]2)cc1)c1ccccc1
InChIKey: NQRGELAKIXGDPL-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 392.26, ALogP 5.24, HBA 2, HBD 2, PSA 57.78, QED 0.5
Compound (SMILES): CC(C)=CCC/C(C)=C/CC/C(C)=C/Cc1c(C)cc(O)c(O)c1O
InChIKey: BACDZNLMIXNCOG-JTCWOHKRSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI insect cells assessed as reduction in formation of 4-quinolinol using kynuramine as substrate preincubated with substrate for 10 mins followed by enzyme addition and measured after 20 mins by fluorescence based microplate reader assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 344.5, ALogP 6.07, HBA 3, HBD 3, PSA 60.69, QED 0.4
Compound (SMILES): O=C(c1ccc(N2N=C(c3ccc(F)cc3)CC2c2cccc3ccccc23)cc1)N1CCOCC1
InChIKey: QTOUVRBRNSQRKV-UHFFFAOYSA-N
Target: Adenomatous polyposis coli protein (SINGLE PROTEIN), Homo sapiens
UniProt: P25054
Assay: Binding affinity to APC (unknown origin) by isothermal titration calorimetry assay
Measurement: Kd = 12800 nM (pChEMBL 4.889999866485596)
Descriptors: MW 479.56, ALogP 5.81, HBA 4, HBD 0, PSA 45.14, QED 0.37
Compound (SMILES): NC(Cc1ccccc1)C(=O)N1CCN(c2ccc3nccn3n2)CC1
InChIKey: GTNOFBUMWPFUNE-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-DTG from recombinant sigma 2 receptor (unknown origin) expressed in baculovirus infected Sf9 cell membranes after 1.5 hrs by scintillation counting analysis
Measurement: Kd > 1000 nM (pChEMBL 6)
Descriptors: MW 350.43, ALogP 0.95, HBA 6, HBD 1, PSA 79.76, QED 0.76
Compound (SMILES): Cc1ccc(CCC(=O)C(=O)NCCc2ccccc2)cc1
InChIKey: FQMIZBVHHLXLIS-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 295.38, ALogP 2.86, HBA 2, HBD 1, PSA 46.17, QED 0.8
Compound (SMILES): COC(=O)CCNC(=O)[C@H]1CC=C(CCC=C(C)C)C[C@@H]1c1ccccc1
InChIKey: UMOKNTQMINGARC-LEWJYISDSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 369.51, ALogP 4.53, HBA 3, HBD 1, PSA 55.4, QED 0.54
Compound (SMILES): CCC(=O)Nc1cc(Nc2nccc(-c3cn(CCO)c4ccccc34)n2)c(OC)cc1F
InChIKey: YJAJIUQWHLPNJW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M mutant (unknown origin) by ELISA
Measurement: IC50 = 170.1 nM (pChEMBL 6.769999980926514)
Descriptors: MW 449.49, ALogP 4.33, HBA 7, HBD 3, PSA 101.3, QED 0.37
Compound (SMILES): CCn1nnc2c(C)c([C@@H](CC(=O)O)c3ccc4c(c3)CN(C(=O)c3c(F)cccc3F)CC4)ccc21
InChIKey: INBSRKBKSGIXCC-NRFANRHFSA-N
Target: Nuclear factor erythroid 2-related factor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16236
Assay: Induction of Nrf2 nuclear translocation in human U2OS cells
Measurement: EC50 = 2390 nM (pChEMBL 5.619999885559082)
Descriptors: MW 504.54, ALogP 4.84, HBA 5, HBD 1, PSA 88.32, QED 0.41
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3ccc(F)cc3)CC2)cc1
InChIKey: ACBPWSNWSZTILP-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 32.4 nM (pChEMBL 7.489999771118164)
Descriptors: MW 391.42, ALogP 1.07, HBA 4, HBD 1, PSA 100.78, QED 0.85
Compound (SMILES): O=C(Nc1ccc(F)cc1-c1cccc(Cl)c1)OCC1CCNCC1
InChIKey: HLWLKLSVJQAUNS-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 362.83, ALogP 4.69, HBA 3, HBD 2, PSA 50.36, QED 0.83
Compound (SMILES): Cc1cccc(-c2nn(CC(=S)Nc3ccccc3F)cc2-c2ccnc(-c3ccccc3)c2)n1
InChIKey: NOEAGWPWMFJLOI-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of recombinant GST-tagged human ALK5 expressed in baculovirus infected Sf9 insect cells
Measurement: IC50 = 2050 nM (pChEMBL 5.690000057220459)
Descriptors: MW 479.58, ALogP 6.56, HBA 5, HBD 1, PSA 55.63, QED 0.28
Compound (SMILES): CC(=O)OCCCCn1c(=O)c(C(=O)NC23CC4CC(CC(C4)C2)C3)c(O)c2nn(C)cc21
InChIKey: QMCHJIHWQUUJNA-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes
Measurement: Ki = 17.3 nM (pChEMBL 7.760000228881836)
Descriptors: MW 456.54, ALogP 2.48, HBA 8, HBD 2, PSA 115.45, QED 0.49
Compound (SMILES): CC(C)(C#N)c1cc(Nc2nc(N3CCC[C@H](N)C3)ncc2C(N)=O)cc(C(C)(C)C#N)c1
InChIKey: RJTDRNOTQRMDCY-KRWDZBQOSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13163
Assay: Inhibition of human MEK5 using ERK5 as substrate in presence of [gamma-33P]-ATP by hotspot kinase assay
Measurement: IC50 = 7680 nM (pChEMBL 5.119999885559082)
Descriptors: MW 446.56, ALogP 2.85, HBA 8, HBD 3, PSA 157.74, QED 0.61
Compound (SMILES): COc1cc(OC)c2c(C3CCNCC3)nc3c(OC)cccc3c2c1
InChIKey: IRVZACWCHIPXKH-UHFFFAOYSA-N
Target: Protein fosB/Transcription factor jun-D (PROTEIN COMPLEX), Homo sapiens
UniProt: P17535
Assay: Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5'-GTCGGTGACTCAAAACA-3' AP1 oligonucleotide measured after 15 mins by fluorescence polarization assay
Measurement: IC50 = 55700 nM (pChEMBL 4.25)
Descriptors: MW 352.43, ALogP 3.88, HBA 5, HBD 1, PSA 52.61, QED 0.72