lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[N+](CC)(CC)CCCCCCCCOc1ccc(/C=C/c2ccccc2)cc1.[I-]
InChIKey: JPHZPBLJNRODIE-LTRPLHCISA-M
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Antagonist activity at human alpha7 nACHR expressed in xenopous laevis oocyte assessed as inhibition of ACh-induced channel current after 5 mins at -70 mV holding potential by two electrode voltage clamp method
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 408.65, ALogP 7.45, HBA 1, HBD 0, PSA 9.23, QED 0.17
Compound (SMILES): COc1ccc2c(=O)cc(C(=O)NCCC3CCN(Cc4ccccc4)CC3)oc2c1
InChIKey: MYWJWRCXIVJIOX-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human 5-lipoxygenase using arachidonic acid as substrate pretreated for 10 mins followed by substrate and ATP addition and measured after 20 mins by H2DCFDA probe based fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 420.51, ALogP 3.83, HBA 5, HBD 1, PSA 71.78, QED 0.63
Compound (SMILES): CC1CC(=O)N2CCCc3cc(C(=O)CCCN4CCC(c5noc6cc(F)ccc56)CC4)cc1c32
InChIKey: XNLUVKGBRJZXII-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserine from serotonin 5-HT2A receptor in rat brain cortex homogenates incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 32.2 nM (pChEMBL 7.489999771118164)
Descriptors: MW 489.59, ALogP 5.6, HBA 5, HBD 0, PSA 66.65, QED 0.42
Compound (SMILES): COc1nc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(=O)(=O)C2CC2)n1
InChIKey: FCIQBOWXMCDHMM-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of human N-terminal GST-tagged ALK G1202R mutant cytoplasmic domain (1058 to 1620 residues) expressed in baculovirus expression system after 1 hr by mobility shift assay
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 545.07, ALogP 3.68, HBA 10, HBD 3, PSA 124.61, QED 0.37
Compound (SMILES): CS(=O)(=O)Nc1nnc2cc(COc3cc(Cl)cc(Cl)c3)c(C3CC3)cn12
InChIKey: DPIPLAYFRAXNRK-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Inhibition of inactivated state of recombinant human NaV1.1 expressed in HEK293 cell membranes coexpressing Nav beta1 subunit assessed as decrease in sodium current amplitude at -40 mV holding potential by PX automated voltage clamp method
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 427.31, ALogP 3.86, HBA 6, HBD 1, PSA 85.59, QED 0.65
Compound (SMILES): COc1ccc(-c2ccc(Sc3cc(=O)n(O)c(=O)[nH]3)cc2)cc1
InChIKey: YLHZCZYVZCUNFO-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 342.38, ALogP 2.6, HBA 6, HBD 2, PSA 84.32, QED 0.56
Compound (SMILES): Cc1c(OCC(O)CN2CCOCC2)cn2ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c12
InChIKey: OFPQHQDWNLXNKV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using poly (Glu, Tyr) 4:1 as substrate after 1 hr by ELISA
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 622.63, ALogP 3.54, HBA 10, HBD 3, PSA 139.55, QED 0.21
Compound (SMILES): Fc1cccc(-c2ccccc2N2CCN(CCc3c[nH]c4ccc(F)cc34)CC2)c1
InChIKey: XQJJMSAULHQJSQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]LSD from recombinant human 5-HT7 receptor expressed in CHO cell membranes after 120 mins by TopCount scintillation counting method
Measurement: Ki = 0.79 nM (pChEMBL 9.100000381469727)
Descriptors: MW 417.5, ALogP 5.48, HBA 2, HBD 1, PSA 22.27, QED 0.46
Compound (SMILES): C[C@H](C(=O)N(Cc1ccc(C2CCOCC2)cc1)c1ccc(C(=O)O)c(O)c1)N(C)S(=O)(=O)c1c(F)c(F)c(F)c(F)c1F
InChIKey: WIYMGDRVBUWGSL-OAHLLOKOSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: In Vitro Assay: Nuclear extract preparations and DNA-binding activity/electrophoretic mobility shift assay (EMSA) were carried out as previously described (Zhang X, et al., (2010) Biochem Pharmacol 79:1398-409; Zhang X, et al., (2012) Proc Natl Acad Sci USA 109:9623-8). The 32P-labeled oligonucleotide probes used were hSIE (high affinity sis-inducible element from the c-fos gene, m67 variant, 5′-AGCTTCATTTCCCGTAAATCCCTA) (SEQ ID NO: 1) that binds Stat1 and Stat3 and MGFe (mammary gland factor element from the bovine β-casein gene promoter, 5′-AGATTTCTAGGAATTCAA) (SEQ ID NO: 2) for Stat1 and Stat5 binding. Except where indicated, nuclear extracts were pre-incubated with compound for 30 min at room temperature prior to incubation with the radiolabeled probe for 30 min at 30° C. before subjecting to EMSA analysis. Where appropriate, bands corresponding to Stat3:DNA complexes were scanned and quantified for each concentration of compound using ImageJ and plotted as percent of control (DMSO) against concentration of compound, from which the IC50 values were derived.
Measurement: IC50 = 11600 nM (pChEMBL 4.940000057220459)
Descriptors: MW 642.6, ALogP 4.92, HBA 6, HBD 2, PSA 124.45, QED 0.19
Compound (SMILES): O=C(Nc1ccc(Oc2c(Br)cnc3[nH]cnc23)c(F)c1)c1cccn(-c2ccc(F)cc2)c1=O
InChIKey: LHGBMCHXJSBVDX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of recombinant GST-tagged human Mer (578 to 872 residues) cytoplasmic domain expressed in Baculovirus system using poly (Glu-Ala-Tyr) peptide as substrate after 5 mins in presence of ADP by fluorescence analysis
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 538.31, ALogP 5.19, HBA 6, HBD 2, PSA 101.9, QED 0.32
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(C(N)=O)cc3)CC2)nc2cc[nH]c12
InChIKey: JRDMIUOVEAYJDY-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 reverse transcriptase infected in human MT4 cells assessed as reduction in biotin-dUTP incorporation
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 495.59, ALogP 4.41, HBA 7, HBD 3, PSA 132.95, QED 0.35
Compound (SMILES): O=c1cc(Cc2cccc(Br)c2)[nH]c(=O)n1O
InChIKey: ZTLSGHFMVYXEKU-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant HIV1 reverse transcriptase RNase H expressed in Escherichia coli JM109 using RNA/DNA duplex substrate HTS1 as substrate
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 297.11, ALogP 1.13, HBA 4, HBD 2, PSA 75.09, QED 0.82
Compound (SMILES): CC1=Nc2c(F)cc(-c3nc(Nc4ccc(C5CCNCC5)cn4)ncc3F)cc2C12CCCC2
InChIKey: OLFNLUGZKOQDEV-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 474.56, ALogP 5.95, HBA 6, HBD 2, PSA 75.09, QED 0.49
Compound (SMILES): CCc1cc2nccc(Nc3n[nH]c(C)c3C)c2cc1S(=O)(=O)C(C)(C)C
InChIKey: ZANVLEPAQZKAAQ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells by Qpatch clamp assay
Measurement: IC50 = 23990 nM (pChEMBL 4.619999885559082)
Descriptors: MW 386.52, ALogP 4.45, HBA 5, HBD 2, PSA 87.74, QED 0.69
Compound (SMILES): O=C1[C@@H]2[C@H](C(=O)N1CCCCN1CCN(c3cccc4c3OCCO4)CC1)[C@H]1C=C[C@@H]2C1
InChIKey: OBKOPYWWTQOWFZ-MTIDIVMFSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 854 nM (pChEMBL 6.070000171661377)
Descriptors: MW 437.54, ALogP 2.17, HBA 6, HBD 0, PSA 62.32, QED 0.39
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc3cn[nH]c3c2)c1
InChIKey: LLIMXLUTGJVMBY-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 335.32, ALogP 2.42, HBA 6, HBD 2, PSA 105.92, QED 0.58
Compound (SMILES): CNc1cc(Nc2cccc3c2OCCO3)nn2c(C(=O)NC3CC3)cnc12
InChIKey: NSKLPBZBZREBGV-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IFNalpha-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 380.41, ALogP 2.18, HBA 8, HBD 3, PSA 101.81, QED 0.62
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(C(=O)C4CCOCC4)CC3)n2c1)S(C)(=O)=O
InChIKey: BGFNEVWDENTDFC-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 580.54, ALogP 3.77, HBA 7, HBD 0, PSA 87.46, QED 0.44
Compound (SMILES): Cc1ccccc1NC(=O)Nc1cc(S(N)(=O)=O)ccc1O
InChIKey: JJLVFDGUWKZSRI-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 19.9 nM (pChEMBL 7.699999809265137)
Descriptors: MW 321.36, ALogP 1.99, HBA 4, HBD 4, PSA 121.52, QED 0.65
Compound (SMILES): COc1cc2c(Nc3ccc(F)c(Cl)c3)c(N)oc2c(C)n1
InChIKey: AXMSFVPTAZTCDK-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 321.74, ALogP 4.26, HBA 5, HBD 2, PSA 73.31, QED 0.75
Compound (SMILES): Nc1oc2c(-c3ccncc3)nccc2c1Nc1ccccc1Cl
InChIKey: XTKSVVQZAHYCGX-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 336.78, ALogP 4.87, HBA 5, HBD 2, PSA 76.97, QED 0.56
Compound (SMILES): Cn1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(CC3COC3)c2=O)cn1
InChIKey: VBAAHLXSBGINKC-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of PARG in human HeLa cells assessed as induction of MMS-induced PAR chains preincubated for 1 hr followed by MMS addition and measured after 1 hr by Alexofluor 488-conjugated secondary antibody and Hoechst 33342 staining based assay
Measurement: EC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 459.53, ALogP 0.42, HBA 9, HBD 1, PSA 117.22, QED 0.55
Compound (SMILES): CCCCC(CCCC(=O)Nc1ccccc1)CCC(=O)NO
InChIKey: UVXBKULTGDABJT-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 in human HeLa-S3 cell lysates preincubated for 15 mins followed by HDAC-Glo substrate addition measured after 30 to 40 mins by fluorimetric method
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 320.43, ALogP 3.89, HBA 3, HBD 3, PSA 78.43, QED 0.43
Compound (SMILES): Nc1oc2c(I)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: BQQCMWQJYJYNEA-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 403.58, ALogP 4.55, HBA 4, HBD 2, PSA 64.08, QED 0.49
Compound (SMILES): CO[C@H]1C[C@H](O[C@H]2CC[C@@]3(C)[C@H](CC[C@@H]4[C@@H]3CC[C@]3(C)[C@@H](C5=CC(=O)OC5)[C@@H](OC(C)=O)C[C@]43O)C2)O[C@@H](C)[C@@H]1O
InChIKey: JLPDBLFIVFSOCC-XYXFTTADSA-N
Target: Glutamate receptor ionotropic, NMDA 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35439
Assay: Binding affinity towards rat Grin1 in an in vitro assay with cellular components measured by membrane filtration
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 576.73, ALogP 3.68, HBA 9, HBD 2, PSA 120.75, QED 0.37
Compound (SMILES): CCOC(=O)c1cnc(NN)n2nc(-c3ccco3)nc12
InChIKey: LZRJTCLKARXZBF-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity by [alpha-32P]ATP based assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 288.27, ALogP 0.85, HBA 9, HBD 2, PSA 120.57, QED 0.41
Compound (SMILES): Cl.O=C(CN1CCC(Cc2ccccc2)CC1)c1ccc2ccccc2c1
InChIKey: QAIYCEDWESWDID-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by Ellman's method
Measurement: IC50 = 9130 nM (pChEMBL 5.039999961853027)
Descriptors: MW 343.47, ALogP 4.98, HBA 2, HBD 0, PSA 20.31, QED 0.61
Compound (SMILES): O=C(NCCC1CCN(Cc2ccccc2)CC1)c1cc(=O)c2cccc(O)c2[nH]1
InChIKey: AZLXAYYWUXDYQA-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human 5-lipoxygenase using arachidonic acid as substrate pretreated for 10 mins followed by substrate and ATP addition and measured after 20 mins by H2DCFDA probe based fluorescence assay
Measurement: IC50 = 77600 nM (pChEMBL 4.110000133514404)
Descriptors: MW 405.5, ALogP 3.27, HBA 4, HBD 3, PSA 85.43, QED 0.59
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCOCCOCCn3cc(CN(CCOc4ccc5c(=O)cc(-c6ccccc6)oc5c4)Cc4ccccc4)nn3)ccc12
InChIKey: CHFFBBULXRPOLU-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 208 nM (pChEMBL 6.679999828338623)
Descriptors: MW 804.9, ALogP 8.02, HBA 12, HBD 0, PSA 131.29, QED 0.07
Compound (SMILES): O=C(O)c1ccc(N2CC3(CCN(Cc4cc(C(F)(F)F)c(Cl)cc4C4CC4)CC3)OC2=O)cc1
InChIKey: BZFUCKCMPOQIKK-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Antagonist activity at mouse SSR5 expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin addition measured after 1 hr by LANCE assay
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 508.92, ALogP 5.93, HBA 4, HBD 1, PSA 70.08, QED 0.54
Compound (SMILES): Cn1nnc(-c2ccnc(-c3cn(Cc4ccccc4Cl)cn3)c2)n1
InChIKey: LULNZVARULNQAH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 351.8, ALogP 2.84, HBA 7, HBD 0, PSA 74.31, QED 0.56
Compound (SMILES): Nc1oc2cnccc2c1Nc1cc(F)c(F)c(Br)c1
InChIKey: JPXLTWOBOAVJQR-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 340.13, ALogP 4.19, HBA 4, HBD 2, PSA 64.08, QED 0.69
Compound (SMILES): Cl.O=C(NCCCCN1CCN(c2cccc(Cl)c2Cl)CC1)c1cc2ccccc2[nH]1
InChIKey: QNFFQBKCWVJYON-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-sulpiride from human D3 receptor expressed in HEK293 cells after 150 mins by liquid scintillation counting method
Measurement: Ki = 15.6 nM (pChEMBL 7.809999942779541)
Descriptors: MW 445.39, ALogP 4.81, HBA 3, HBD 2, PSA 51.37, QED 0.51
Compound (SMILES): CNc1ncc(C(=O)NCc2ccc(-c3ccccc3)cc2)c2nc(-c3ccco3)nn12
InChIKey: LRBRBZRXARFWFP-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity by [alpha-32P]ATP based assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 424.46, ALogP 4.02, HBA 7, HBD 2, PSA 97.35, QED 0.43
Compound (SMILES): CN1CCN(C2CCN(C(=O)COc3ccc(-c4ccccc4)cc3)CC2)CC1
InChIKey: MOQQZFPQHVEHKY-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Anopheles gambiae
UniProt: Q869C3
Assay: Inhibition of recombinant Anopheles gambiae AChE1 G122S mutant expressed in sf9 insect cells using acetylthiocholine iodide as substrate measured over 60 secs by Ellman assay
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 393.53, ALogP 2.97, HBA 4, HBD 0, PSA 36.02, QED 0.78
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2Cc2ccccc2)c1
InChIKey: SAXXFJQUHSPIPP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 279.3, ALogP 2.56, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): C=CCOC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1OC(=O)[C@H]1[C@@H](C)CC)C(C)C)C(C)C
InChIKey: HCQRRPYERGCDMA-QUSNUVHPSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human Jurkat cell lysate using Suc-LLVY-AMC as substrate pretreated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 410.51, ALogP 1.58, HBA 6, HBD 2, PSA 110.8, QED 0.4
Compound (SMILES): Cc1cc(C)cc(Nc2cc(Nc3ccccc3)c3ncc(C(N)=O)n3n2)c1
InChIKey: IFEXEXRVVLLXPF-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IFNalpha-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 372.43, ALogP 3.93, HBA 6, HBD 3, PSA 97.34, QED 0.49
Compound (SMILES): Cc1ccc(C2=Nc3c(n[nH]c3C)Nc3nc(NC(C)(C)C)ncc32)cc1
InChIKey: QTJFIGDMMIYLER-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged KDR (790 to end residues) expressed in baculovirus infected Sf21 insect cells after 60 mins by ELISA
Measurement: IC50 = 84.5 nM (pChEMBL 7.070000171661377)
Descriptors: MW 361.45, ALogP 4.25, HBA 6, HBD 3, PSA 90.88, QED 0.5
Compound (SMILES): Cc1nn(C(=O)OC(C)(C)C)c(N)c1-c1ccc(Cl)c(Cl)c1
InChIKey: CTCULZLBPOLAKH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged NIK (M1 to P947 residues) expressed in Sf9 insect cells using AKDVDQGSLCTSFVGTLQY peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 342.23, ALogP 4.53, HBA 5, HBD 1, PSA 70.14, QED 0.83
Compound (SMILES): Cc1nc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)co1
InChIKey: YBHPSBQYBQRDEV-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 372.33, ALogP 3.25, HBA 7, HBD 2, PSA 88.76, QED 0.78
Compound (SMILES): N#CC1(c2cc(Nc3nc(NC4CCC(F)(F)CC4)nc(-n4ccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: POHHIURFWMYFGA-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 505.46, ALogP 4.76, HBA 9, HBD 2, PSA 117.23, QED 0.46
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H]3C(=O)N(C)CC(=O)N23)s1
InChIKey: WNVDDMMDUVNDAO-OXQOHEQNSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PDE2A (2 to 941 residues) expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 379.49, ALogP 3.11, HBA 3, HBD 1, PSA 56.41, QED 0.74
Compound (SMILES): CCc1nccc2c(Nc3cccc(C(F)(F)F)c3)c(N)oc12
InChIKey: KUJVWFVTDJCVDN-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 321.3, ALogP 4.73, HBA 4, HBD 2, PSA 64.08, QED 0.73
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2ccccc2F)n1)C1CC1
InChIKey: SBWSJSCKQBEYEK-VXGBXAGGSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 341.43, ALogP 4.1, HBA 5, HBD 2, PSA 62.73, QED 0.79
Compound (SMILES): Fc1ccc(-c2c(-c3cc(-c4nn[nH]n4)ccn3)ncn2CC2CC2)cc1
InChIKey: KCJJYCIVFYDIRB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 361.38, ALogP 3.34, HBA 6, HBD 1, PSA 85.17, QED 0.59
Compound (SMILES): C[C@@H](CC(=O)N1CCC(O)(Cn2cnc3c(-c4ccc(CN)cc4)n(C)nc3c2=O)CC1)c1ccccc1
InChIKey: DGHAUZFDWIZFRM-FQEVSTJZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using Ub-Rho110 as substrate by fluorescence based SPR analysis
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 514.63, ALogP 2.8, HBA 8, HBD 2, PSA 119.27, QED 0.39
Compound (SMILES): CCCCc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: YHNFXISQPODBJA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 245.28, ALogP 2.31, HBA 4, HBD 1, PSA 68.01, QED 0.88
Compound (SMILES): CCOC(=O)c1nn(C)c2c1C(C)Cc1cnc(Nc3ccccc3)nc1-2
InChIKey: BSIPNJIOPDWDSK-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.42, ALogP 3.46, HBA 7, HBD 1, PSA 81.93, QED 0.72
Compound (SMILES): O=S(=O)(Nc1nnc2cc(OCC34CC5CC(CC(C5)C3)C4)c(C3CC3)cn12)C1CCC1
InChIKey: SVPCWDMKWCXQFX-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay (EP) (In Vitro Assay): The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured using the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaC12, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaC12, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. In some studies, the external sodium was reduced by equimolar replacement with choline. Osmolarity in the CsF internal and NaCl external solutions was adjusted to 300 mOsm/kg and 310 mOsm/kg with glucose, respectively. All recordings were performed at ambient temperature in a bath chamber with a volume of 150 μL. Control sodium currents were measured in 0.5% DMSO. Controls and representative compounds of the invention were applied to the recording chamber through a 4-pinch or 8-pinch valve bath perfusion system manufactured by ALA Scientific Instruments.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 456.61, ALogP 4.5, HBA 6, HBD 1, PSA 85.59, QED 0.66
Compound (SMILES): O=S(=O)(CCCCl)N1CCN(c2ccc(/C=C/c3cc(Cl)cc(Cn4ccnc4)c3)cc2)CC1
InChIKey: BEEQSJMIBJVSRU-NSCUHMNNSA-N
Target: Steroid 21-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: P08686
Assay: Inhibition of recombinant CYP21 (unknown origin) expressed in human AD293 cells using 17alpha-hydroxyprogesterone as substrate pretreated for 60 mins followed by substrate addition and measured after 45 mins by LC/MS analysis
Measurement: IC50 = 2870 nM (pChEMBL 5.539999961853027)
Descriptors: MW 519.5, ALogP 4.84, HBA 5, HBD 0, PSA 58.44, QED 0.3
Compound (SMILES): CCOC(=O)c1c(-c2ccc(Cl)c(Cl)c2)[nH]c2c1cc(O)c1ccccc12
InChIKey: WEIJKEYQWOSYEJ-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES-1 in microsomal membranes isolated from IL-1beta-stimulated human A549 cells preincubated for 15 mins followed by PGH2 addition measured after 1 mins by RP-HPLC analysis
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 400.26, ALogP 6.18, HBA 3, HBD 2, PSA 62.32, QED 0.4
Compound (SMILES): CCOC(=O)c1cnc(N2CCNCC2)n2nc(-c3ccco3)nc12
InChIKey: VZYYRUGCZSBASL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity by [alpha-32P]ATP based assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 342.36, ALogP 0.97, HBA 9, HBD 1, PSA 97.79, QED 0.7
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc(F)c(-c4cc(F)c5c(c4)C4(CCCC4)C(C)=N5)n3)nc2)CC1
InChIKey: FOLRMJVSUYSNKR-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 503.6, ALogP 5.62, HBA 7, HBD 1, PSA 69.54, QED 0.49
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)c1ccc(Cl)cc1
InChIKey: LYECZDRRRZNARD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 356.81, ALogP 3.43, HBA 5, HBD 1, PSA 71.25, QED 0.73
Compound (SMILES): CC[C@H](C(=O)N1CC(C#N)C1)n1c(=O)c2cc(OC)c(OC)cc2c2cnc3[nH]ccc3c21
InChIKey: ZDNBWZRRFSXDFS-GOSISDBHSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter-binding method
Measurement: IC50 = 29.6 nM (pChEMBL 7.53000020980835)
Descriptors: MW 445.48, ALogP 2.98, HBA 7, HBD 1, PSA 113.24, QED 0.47
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3cc(-c4ccncc4)c[nH]c3=O)cc2)CC1
InChIKey: GPWFEKSGAWXQOP-UHFFFAOYSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQS7
Assay: Inhibition of human full length N-terminal GST-tagged Aurora B (1 to 344 end residues)/His-tagged INCENP (803 to 918 end residues) expressed in baculovirus expression system using fluorescence-labeled FL-Peptide 21 as substrate after 60 mins in presence of ATP by fluorescence assay based Cheng-Prusoff equation analysis
Measurement: Ki = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 389.46, ALogP 2.44, HBA 5, HBD 2, PSA 81.33, QED 0.72
Compound (SMILES): O=C(Nc1ccncc1)c1ccc(COc2ccccc2Cl)cc1
InChIKey: VAHVWEIUWRWGMO-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of delta-5 fatty acid desaturase (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 338.79, ALogP 4.57, HBA 3, HBD 1, PSA 51.22, QED 0.74
Compound (SMILES): Cc1ccc(COc2ccnn2-c2cc(C(=O)O)ccn2)cc1Cl
InChIKey: BJFOUULYELAMPD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 343.77, ALogP 3.51, HBA 5, HBD 1, PSA 77.24, QED 0.77
Compound (SMILES): Cc1ccc(-c2c(N)n[nH]c2C)cc1
InChIKey: FIQXGADANMRLKW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged NIK (M1 to P947 residues) expressed in Sf9 insect cells using AKDVDQGSLCTSFVGTLQY peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 187.25, ALogP 2.28, HBA 2, HBD 2, PSA 54.7, QED 0.72
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1OC(=O)[C@H]1C(C)C)C(=O)N[C@H](C(=O)OCc1ccccc1)C(C)C
InChIKey: NEQHFOKLQNEKPO-LWYYNNOASA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human immunoproteasome beta5 subunit using Suc-RLR-AMC as substrate pretreated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 44.7 nM (pChEMBL 7.349999904632568)
Descriptors: MW 446.54, ALogP 2.21, HBA 6, HBD 2, PSA 110.8, QED 0.53
Compound (SMILES): CN(CCc1cnn(-c2cc(C(=O)NC#N)ccn2)c1)Cc1ccc(F)cc1
InChIKey: QXPNFUDMDNCVJO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 378.41, ALogP 2.29, HBA 6, HBD 1, PSA 86.84, QED 0.5
Compound (SMILES): Cc1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(CC3CC3)c2=O)on1
InChIKey: BPNAFLANHVBAPX-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of PARG in human HeLa cells assessed as induction of MMS-induced PAR chains preincubated for 1 hr followed by MMS addition and measured after 1 hr by Alexofluor 488-conjugated secondary antibody and Hoechst 33342 staining based assay
Measurement: EC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 444.51, ALogP 1.75, HBA 8, HBD 1, PSA 116.2, QED 0.59
Compound (SMILES): O=c1cc(Sc2ccc(-c3cccc(C(F)(F)F)c3)cc2)[nH]c(=O)n1O
InChIKey: XCRSZKWDHUVLFK-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 380.35, ALogP 3.61, HBA 5, HBD 2, PSA 75.09, QED 0.54
Compound (SMILES): Fc1ccc2[nH]cc(CCCN3CCN(c4ccccc4-c4ccccc4)CC3)c2c1
InChIKey: IDAPODLHCQBQIS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]LSD from recombinant human 5-HT7 receptor expressed in CHO cell membranes after 120 mins by TopCount scintillation counting method
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 413.54, ALogP 5.73, HBA 2, HBD 1, PSA 22.27, QED 0.44
Compound (SMILES): N#CC1(c2cc(Nc3nc(N[C@H]4CCC(F)(F)C4)nc(-c4ccnc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: WMHFZXFIAKEFCS-ZDUSSCGKSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 503.44, ALogP 4.64, HBA 9, HBD 2, PSA 125.19, QED 0.46
Compound (SMILES): Cn1cnc(-c2cc3[nH]nnc3cn2)c1-c1ccc(F)cc1
InChIKey: DFIZSWCEVFIDEP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 294.29, ALogP 2.56, HBA 5, HBD 1, PSA 72.28, QED 0.62
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C(=O)Nc3ccccc3F)cc2)cc1
InChIKey: MEJYFHSTMVGYPM-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: Transrepression of RORgammat in anti-CD3/CD28 stimulated C57BL/6 mouse CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by measuring reduction in IL-17A level after 4 days by ELISA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 482.58, ALogP 4.72, HBA 4, HBD 2, PSA 92.34, QED 0.49
Compound (SMILES): CC1=C(/C=C/C(C)=C/C=C/C(C)=C/C(=O)C(Cl)Cl)C(C)(C)CCC1
InChIKey: NWWAQIKCANAFJE-YCNIQYBTSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Gallus gallus
UniProt: P27463
Assay: Inhibition of N-terminal His6-tagged recombinant chick RALDH1 expressed in Escherichia coli BL21(DE3) cells using RAL as substrate measured after 30 mins in presence of NADH by Morrison's plot analysis
Measurement: Ki = 194.4 nM (pChEMBL 6.710000038146973)
Descriptors: MW 367.36, ALogP 6.89, HBA 1, HBD 0, PSA 17.07, QED 0.28
Compound (SMILES): CCCCCc1cc(O)c2c(c1)OC(C)(C)C1=C2C(O)C(C)(OC)CC1
InChIKey: IXTZSRZHCVQVPJ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from recombinant human full length CB2 receptor expressed in HEK293 cell membranes after 90 mins by topcount method
Measurement: IC50 = 599 nM (pChEMBL 6.21999979019165)
Descriptors: MW 360.49, ALogP 4.61, HBA 4, HBD 2, PSA 58.92, QED 0.75
Compound (SMILES): C=C1C(=O)N[C@@H](C)C(=O)N(C)[C@@H](C)C(=O)N[C@@H]([C@H](OC(=O)[C@@H](NC(C)=O)[C@H](O)C(C)C)C(C)C)C(=O)N(C)[C@@H]([C@@H](C)OC)C(=O)O[C@@H](C)[C@H](NC(C)=O)C(=O)O[C@H](Cc2ccccc2)C(=O)N1C
InChIKey: QVYLWCAYZGFGNF-MCURUZIASA-N
Target: Guanine nucleotide-binding protein subunit alpha-11 (SINGLE PROTEIN), Homo sapiens
UniProt: P29992
Assay: Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 960.09, ALogP -0.65, HBA 15, HBD 5, PSA 285.69, QED 0.1
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)c(=O)n(C(C)C)c3cnc(Nc4ccc(OCCN(C)C)cc4OC)nc32)c1
InChIKey: WSUUQWSGDOKKOY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR kinase domain (unknown origin) expressed using baculovirus expression system incubated for 1 hr using Poly(Glu,Tyr) 4:1 by ELISA method
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 559.63, ALogP 3.34, HBA 11, HBD 2, PSA 132.61, QED 0.21
Compound (SMILES): CCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCc3ccc(F)cc3)cc2)n(CCC)c1=O
InChIKey: RTJXZSORXGMCBF-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-602 from human adenosine A2B receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 576.67, ALogP 3.47, HBA 9, HBD 1, PSA 103.39, QED 0.28
Compound (SMILES): CC(C)n1cc(CN2CCC3(CC2)CN(c2ccc(C(=O)O)cc2)C(=O)O3)c2c(C3CC3)cccc21
InChIKey: JCVUXKREYYXKDC-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Antagonist activity at mouse SSR5 expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin addition measured after 1 hr by LANCE assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 487.6, ALogP 5.79, HBA 5, HBD 1, PSA 75.01, QED 0.48
Compound (SMILES): Cc1cc(-c2ccc(C(=O)c3cc(F)c(F)c(O)c3F)s2)cc(C)c1O
InChIKey: BVLIRXILWDNARH-UHFFFAOYSA-N
Target: Estradiol 17-beta-dehydrogenase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P51658
Assay: Inhibition of mouse microsomal fraction 17beta-HSD2 using [3H]-E2 as substrate after 20 mins in presence of NAD+ by radio-flow detector based analysis
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 378.37, ALogP 5.09, HBA 4, HBD 2, PSA 57.53, QED 0.49
Compound (SMILES): Cc1cc(-c2ccc(Sc3cc(=O)n(O)c(=O)[nH]3)cc2)ccc1F
InChIKey: VDQCAWVZNGUPNL-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 344.37, ALogP 3.04, HBA 5, HBD 2, PSA 75.09, QED 0.57
Compound (SMILES): O=C(O)CCCC(=O)Nc1cc(Nc2cccc(Br)c2)ncn1
InChIKey: YHWBXXDXRARKGF-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P21860
Assay: Inhibition of recombinant human GST-tagged EGFR L858R mutant cytoplasmic domain expressed in baculovirus expression system using FAM-labeled peptide as substrate after 10 mins by mobility shift assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 379.21, ALogP 3.18, HBA 5, HBD 3, PSA 104.21, QED 0.68
Compound (SMILES): Cc1cc(O)n(-c2cc(C(=O)O)ccn2)n1
InChIKey: KAHITAMALHBXDQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 219.2, ALogP 0.98, HBA 5, HBD 2, PSA 88.24, QED 0.79