lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H](Nc1cc(NC(C)(C)C)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: SICOBUZBFFTRIB-LLVKDONJSA-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 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 379.43, ALogP 4.98, HBA 5, HBD 2, PSA 62.73, QED 0.77
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OC[C@H]2COc3ccc(Cl)cc3O2)cc1
InChIKey: SVPBWNODTIJLNU-YJBOKZPZSA-N
Target: ATP-binding cassette sub-family C member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92887
Assay: Inhibition of human MRP2
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 386.83, ALogP 4.14, HBA 4, HBD 1, PSA 64.99, QED 0.76
Compound (SMILES): CCCCC[C@H](C)Nc1ncc2c(-c3ccc(CN4CCN(C)CC4)cc3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: WDLJSYMVGMNFSD-YGPDHOBYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) using 5'-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 518.75, ALogP 5.7, HBA 7, HBD 2, PSA 69.45, QED 0.34
Compound (SMILES): CCC(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]n3)ccn2)c1
InChIKey: RFGNJZHABKKPLK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli 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 331.38, ALogP 3.12, HBA 6, HBD 1, PSA 85.17, QED 0.61
Compound (SMILES): CC(CC#N)Nc1nc(NC(C)CC#N)nc(-c2cccc(Cl)n2)n1
InChIKey: NTLZDWVSKRAINR-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 6 hrs before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 356.82, ALogP 3.02, HBA 8, HBD 2, PSA 123.2, QED 0.73
Compound (SMILES): CN(C)c1nc(NC(=O)c2ccccc2)sc1C(=O)c1cnc(N)n1-c1ccc(Cl)cc1
InChIKey: XUUPIQPJPCUEKX-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at recombinant human A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 466.95, ALogP 4.11, HBA 8, HBD 2, PSA 106.14, QED 0.41
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)CC1CC1
InChIKey: MBHMCPDRAOESBT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli 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 300.36, ALogP 1.99, HBA 5, HBD 1, PSA 71.25, QED 0.85
Compound (SMILES): Nc1oc2cnccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: MAFDXEXXQIAQTR-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Inhibition of recombinant human C-terminal polyHis-tagged IDO2 (Met14 to Gly420 residues) expressed in Escherichia coli assessed as reduction in kynurenine formation using tryptophan as substrate measured by LC/MS/MS analysis
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 277.69, ALogP 3.95, HBA 4, HBD 2, PSA 64.08, QED 0.74
Compound (SMILES): CCc1ccc(-c2c(-c3cc(C(=O)O)ccn3)ncn2C)cc1
InChIKey: YIYGVYOANZWNAL-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 307.35, ALogP 3.41, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](Cc1ccc(C(F)(F)F)c(Cl)c1)C(=O)N1CCC[C@@H]1c1cncc(Cc2ccccc2)n1
InChIKey: SZOGURXUQQJNKI-ZNCVFPSASA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from N-terminal His-tagged human recombinant XIAP BIR3 (253 to 347 residues) expressed in Escherichia coli BL21(DE3) Gold after 1 hr by DELFIA
Measurement: IC50 = 175.9 nM (pChEMBL 6.75)
Descriptors: MW 574.05, ALogP 4.74, HBA 5, HBD 2, PSA 87.22, QED 0.39
Compound (SMILES): N#CC1(c2cc(Nc3nc(NC4CC5(C4)CC(F)(F)C5)nc(-c4cccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: GQVWKEOJLWNAAS-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 528.49, ALogP 5.64, HBA 8, HBD 2, PSA 112.3, QED 0.4
Compound (SMILES): CC(Nc1nc(Nc2cc(F)cc(F)c2)nc(-n2ccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: AQCLVWSTMGVZRR-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 453.3, ALogP 4.46, HBA 7, HBD 2, PSA 80.55, QED 0.56
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1cc(F)c(F)cc1OCC1CC1
InChIKey: PZUPDEOZRJAYNQ-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, and 5 μM ammonium iron(II) sulfate. Reaction product was 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 were 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 was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl 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 were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 385.37, ALogP 3.91, HBA 5, HBD 1, PSA 77.24, QED 0.7
Compound (SMILES): FC1(F)CC(Nc2nc(NC3CC(F)(F)C3)nc(-c3nc(C(F)(F)F)cs3)n2)C1
InChIKey: DSJXHLDOLTTWGN-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 442.36, ALogP 4.43, HBA 7, HBD 2, PSA 75.62, QED 0.67
Compound (SMILES): C=CC(=O)Nc1cccc(-c2ncnc3[nH]cc(CCOC)c23)c1
InChIKey: HPOCKNFSXXGFOP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 322.37, ALogP 2.94, HBA 4, HBD 2, PSA 79.9, QED 0.68
Compound (SMILES): CCOc1cc(-c2c(-c3cc(-c4c[nH]nn4)ccn3)ncn2C)ccc1F
InChIKey: JYWWWRWPSHBPRZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: FBXL11 Assay: The ability of test compounds to inhibit the activity of FBXL11 was determined in 384-well plate format under the following reaction conditions: 0.15 nM FBXL11, 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 0.45 nM FBXL11 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 rt for 40 min, followed by addition of 3 μl 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 hr incubation at rt. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 364.38, ALogP 3.47, HBA 6, HBD 1, PSA 81.51, QED 0.59
Compound (SMILES): COc1ccc(/C=C2\SC(=S)NC2=O)cc1C#C[Si](C)(C)C
InChIKey: JHFDWHHUUUMRLK-UVTDQMKNSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 8313 nM (pChEMBL 5.079999923706055)
Descriptors: MW 347.54
Compound (SMILES): C[C@@H]1O[C@@H](n2c3ccc(O)cc3c3c4c(c5c6ccccc6[nH]c5c32)CNC4=O)C[C@@H](N)[C@H]1O
InChIKey: AARICDGIAQPTML-RBFJYNKASA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKCtheta (unknown origin) by HTRF assay
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 456.5, ALogP 3.37, HBA 6, HBD 5, PSA 125.53, QED 0.26
Compound (SMILES): O=C(O)CC1COc2cc(OCCCOc3cccc(Br)c3)ccc21
InChIKey: QMCXGQFVAXBZTK-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human GAL4 fused PPARalpha-LBD expressed in human HepG2 cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 407.26, ALogP 4.25, HBA 4, HBD 1, PSA 64.99, QED 0.66
Compound (SMILES): CS(=O)(=O)Nc1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(C(=O)C4COC4)CC3)n2c1
InChIKey: WTZSDYCVUGINNX-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 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 538.46, ALogP 2.97, HBA 7, HBD 1, PSA 96.25, QED 0.52
Compound (SMILES): O=C1S/C(=C\c2ccc(N3CCOCC3)c(Cl)c2)C(=O)N1c1ccc(OCCCN2CCN(CC3CC3)CC2)cc1
InChIKey: LPTYQBTUWHUZEM-ANYBSYGZSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Irreversible inhibition of IKKbeta (unknown origin) using IkappaBalpha-derived 5FAMGRHDSGLDSMK-NH2 as substrate measured after 60 mins
Measurement: IC50 = 252.35 nM (pChEMBL 6.599999904632568)
Descriptors: MW 597.18, ALogP 5.21, HBA 8, HBD 0, PSA 65.56, QED 0.27
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)F)n2)n1)C1CC1
InChIKey: OHIIKMKNLSEDJI-GHMZBOCLSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 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 374.44, ALogP 4.29, HBA 6, HBD 2, PSA 75.62, QED 0.72
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1ccc(OC(F)(F)F)cc1
InChIKey: OTBZGJHFGXDSHF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 363.3, ALogP 3.75, HBA 5, HBD 1, PSA 77.24, QED 0.76
Compound (SMILES): C[C@H](CC(=O)N1CCC(O)(Cn2cnc3c(-c4ccc(CN)cc4)n(C)nc3c2=O)CC1)c1ccccc1
InChIKey: DGHAUZFDWIZFRM-HXUWFJFHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using Ub-Rho110 as substrate by SPR analysis
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 514.63, ALogP 2.8, HBA 8, HBD 2, PSA 119.27, QED 0.39
Compound (SMILES): CNc1ncc(C(=O)OCc2ccccc2Cl)c2nc(-c3ccco3)nn12
InChIKey: WBMARTCQUWTJOJ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki = 6.05 nM (pChEMBL 8.220000267028809)
Descriptors: MW 383.8, ALogP 3.44, HBA 8, HBD 1, PSA 94.55, QED 0.53
Compound (SMILES): Cc1nn(C(=O)c2ccc3ccccc3c2)c(C)c1Cl
InChIKey: UACABVLDFJEHQH-UHFFFAOYSA-N
Target: Alkaline phosphatase, tissue-nonspecific isozyme (SINGLE PROTEIN), Homo sapiens
UniProt: P05186
Assay: Inhibition of human TNAP expressed in COS7 cells using CDP-star as substrate preincubated for 5 to 10 mins followed by substrate addition measured after 20 mins by luminescence-based assay
Measurement: IC50 = 19100 nM (pChEMBL 4.71999979019165)
Descriptors: MW 284.75, ALogP 4, HBA 3, HBD 0, PSA 34.89, QED 0.68
Compound (SMILES): N#CNC1CCOc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: XUOPPKZGCWSZIU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 = 1179 nM (pChEMBL 5.929999828338623)
Descriptors: MW 291.31, ALogP 2.52, HBA 5, HBD 2, PSA 86.62, QED 0.56
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(-c3cccc(CN4CCN(C)CC4)c3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: QGVUAUSZGWKGSS-TUSQITKMSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) using 5'-FAM-KKKKEEIYFFF-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 316 nM (pChEMBL 6.5)
Descriptors: MW 490.7, ALogP 4.92, HBA 7, HBD 2, PSA 69.45, QED 0.47
Compound (SMILES): CCC(CCCC(=O)Nc1ccccc1)CCC(=O)NO
InChIKey: SAZYUSNRLANPTC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 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 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 292.38, ALogP 3.11, HBA 3, HBD 3, PSA 78.43, QED 0.48
Compound (SMILES): Fc1cc(F)c(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)c(F)c1
InChIKey: HUYPSMCWEAVAHQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: Inhibition of recombinant human C-terminal FLAG-tagged JMJD3 (1043 to end residues) expressed in baculovirus infected Sf9 cells using H3K27me3-biotin labelled peptide as substrate measured after 20 mins by AlphaScreen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 438.33, ALogP 4.41, HBA 5, HBD 1, PSA 72.28, QED 0.47
Compound (SMILES): Cc1ccc(Oc2c(C)nn(C(=O)c3ccc(Cl)cc3)c2C)cc1
InChIKey: YOHYRFFFGAVVED-UHFFFAOYSA-N
Target: Alkaline phosphatase, tissue-nonspecific isozyme (SINGLE PROTEIN), Homo sapiens
UniProt: P05186
Assay: Inhibition of human TNAP expressed in COS7 cells using CDP-star as substrate preincubated for 5 to 10 mins followed by substrate addition measured after 20 mins by luminescence-based assay
Measurement: IC50 = 5780 nM (pChEMBL 5.239999771118164)
Descriptors: MW 340.81, ALogP 4.94, HBA 4, HBD 0, PSA 44.12, QED 0.68
Compound (SMILES): CC(=O)n1nc(C)c(Br)c1N
InChIKey: ODPPMYVGATVMNO-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 218.05, ALogP 1.2, HBA 4, HBD 1, PSA 60.91, QED 0.71
Compound (SMILES): O=S(=O)(c1cccc(OC(F)(F)F)c1)N1CCN(c2ccc(/C=C/c3cc(Cl)cc(Cn4ccnc4)c3)cc2)CC1
InChIKey: CLGREMZLJSBCJH-SNAWJCMRSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of CYP19 (unknown origin)
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 603.07, ALogP 6.16, HBA 6, HBD 0, PSA 67.67, QED 0.23
Compound (SMILES): COc1ncc(-c2ccc3ncc(Cl)c(=O)n3c2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: LQTYGHZRBUVRMR-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate after 30 mins by HTRF assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 478.86, ALogP 3.5, HBA 7, HBD 1, PSA 102.66, QED 0.47
Compound (SMILES): Cc1coc2c1C(=O)C(=O)c1c-2ccc2c1C=CCC2(C)C
InChIKey: PURTYNPVRFEUEN-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R4B8
Assay: Inhibition of NLRP3 inflammasome in mouse J774.A1 cells assessed as inhibition of IL-1 beta secretion
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 292.33, ALogP 4.33, HBA 3, HBD 0, PSA 47.28, QED 0.68
Compound (SMILES): Cc1nn(C(=O)C2CC2)c(N)c1-c1ccc(Cl)c(Cl)c1
InChIKey: DQSCANUIKKBERK-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 310.18, ALogP 3.8, HBA 4, HBD 1, PSA 60.91, QED 0.92
Compound (SMILES): COc1ccc(CN2CCC(CCNC(=O)/C=C/c3cc(C(C)(C)C)c(O)c(C(C)(C)C)c3)CC2)cc1
InChIKey: RXFASTRSJRIBEQ-JLHYYAGUSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B using p-tyramine as substrate incubated for 15 mins followed by substrate addition measured for 20 mins by fluorescence assay
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 506.73, ALogP 6.43, HBA 4, HBD 2, PSA 61.8, QED 0.41
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N(C)[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: DIGJQFAKFJVPSH-GONAQTSYSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 4064.54
Compound (SMILES): COC(=O)N1CCN([C@H]2CC[C@H](Nc3ncnn4ccc(C(C)C)c34)CC2)CC1
InChIKey: ARNKXWVHOPUZBD-QAQDUYKDSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human KARPAS299 cells assessed as reduction in IL-1 stimulated IRAK4 phosphorylation at Thr345/Ser346 residues preincubated for 1 hr followed by IL-1 stimulation for 10 mins by flow cytometry analysis
Measurement: IC50 = 363.08 nM (pChEMBL 6.440000057220459)
Descriptors: MW 400.53, ALogP 2.96, HBA 7, HBD 1, PSA 75, QED 0.85
Compound (SMILES): Cc1ccc(Cc2cc(O)n(-c3cc(C(=O)O)ccn3)n2)c(F)c1
InChIKey: OUHLSUWZMMWTNI-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, and 5 μM ammonium iron(II) sulfate. Reaction product was 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 were 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 was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl of 50 m/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 were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 327.31, ALogP 2.71, HBA 5, HBD 2, PSA 88.24, QED 0.77
Compound (SMILES): O=C(OC1=CS(=O)(=O)Nc2ccc(Oc3ccccc3Br)cc21)c1ccc(F)c(F)c1
InChIKey: ZCQLLKXWSFUGPP-UHFFFAOYSA-N
Target: Nonstructural protein 5 (SINGLE PROTEIN), Dengue virus
UniProt: V5TFZ2
Assay: Mixed type inhibition of DENV3 NS5 RdRp using increasing concentration of GTP as substrate assessed as free enzyme after 1 hr in presence of ss-RNA PolyC template by Lineweaver-Burk double reciprocal plot analysis
Measurement: Ki = 251.9 nM (pChEMBL 6.599999904632568)
Descriptors: MW 508.3, ALogP 5.43, HBA 5, HBD 1, PSA 81.7, QED 0.48
Compound (SMILES): CCC1(CC)C(C)=Nc2c(F)cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)cc21
InChIKey: HOKDQPMWTBQYHL-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Kinase Inhibitory Activity Assay:     1.2.2 Preparation of kinase solution: Kinase solutions having the concentrations required for each reaction system were prepared from 100 ng/μl kinase stock solution and the 1× kinase reaction buffer.    1.2.3 Preparation of the test compound solution and control LY2835219 solution:      (1) Preparation of control LY2835219 solution        a. 1 μl of 10 mM standard substance stock solution was taken and added to 9 μl of kinase reaction buffer I and mixed well; then 90 μl of kinase reaction buffer I was added and mixed well; then 100 μl of kinase reaction buffer I was added and mixed well. The final concentration was 50 μM.        b. 40 μl of kinase reaction buffer II was added into B2 to B10 of a 96-well plate, and 50 μl of the above solution was added into B1;        c. 10 μl of solution was taken from well B1, added into B2, and mixed well; then 10 μl of the resulting solution was taken and added into B3, and dilution was carried out in sequence to B9, so as to obtain control solutions that are diluted by 5-fold sequentially.      (2) Preparation of test compound solution:        a. Test compound solutions at a certain concentration were taken, respectively, diluted with kinase reaction buffer I to a final concentration of 50 μM compound solution;        b. 40 μl of kinase reaction buffer II was added into H2 to H10 of the 96-well plate; and 50 μl of the above solution was added into H1;        c. 10 μl of solution was taken from well H1, added into H2, and mixed well; then 10 μl of the resulting solution was taken and added into H3, and dilution was carried out in sequence to H9, so as to obtain test compound solutions that are diluted by 5-fold sequentially.    1.2.4 Preparation of a mixed solution of reaction substrate and ATP:      a. Preparation of ATP solution:      200 μl of 0.1 mM ATP solution: 2 μl of 10 mM ATP was added to 198 μl of kinase reaction buffer I;      300 μl of 50 μM ATP solution: 150 μl of kinase reaction buffer I was added to 150 μl of the above 0.1 mM ATP solution;      b. Preparation of 300 μl of reaction substrate solution:      150 μl 1 μg/μl reaction substrate stock solution was added to 150 μl kinase reaction buffer I, and mixed well;      c. The above a/b solutions were mixed to obtain mixed solutions, respectively.
Measurement: IC50 = 3.15 nM (pChEMBL 8.5)
Descriptors: MW 477.56, ALogP 5.13, HBA 7, HBD 2, PSA 78.33, QED 0.51
Compound (SMILES): Cc1[nH]nc(N)c1-c1ccc2ccccc2c1
InChIKey: OLSXZQGKTNNHGF-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 223.28, ALogP 3.12, HBA 2, HBD 2, PSA 54.7, QED 0.67
Compound (SMILES): FC1(F)CC2(CC(Nc3nc(Nc4ccnc(C(F)(F)F)c4)nc(-c4cccc(C(F)(F)F)n4)n3)C2)C1
InChIKey: BTPLBROFKCBOEI-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 531.41, ALogP 6.1, HBA 7, HBD 2, PSA 88.51, QED 0.38
Compound (SMILES): Cc1ccc2oc(-c3ccc(OCCCCc4cn(CCOCCOc5ccc(-c6cc(=O)c7cc(F)ccc7o6)cc5)nn4)cc3)cc(=O)c2c1
InChIKey: PILXOFXFXWCCHT-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 155.7 nM (pChEMBL 6.809999942779541)
Descriptors: MW 701.75, ALogP 7.77, HBA 10, HBD 0, PSA 118.82, QED 0.1
Compound (SMILES): Cc1ccc(Cn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: BHPBVHSFDSZGKN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: Inhibition of recombinant human C-terminal FLAG-tagged JMJD3 (1043 to end residues) expressed in baculovirus infected Sf9 cells using H3K27me3-biotin labelled peptide as substrate measured after 20 mins by AlphaScreen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.37, ALogP 4.11, HBA 5, HBD 1, PSA 72.28, QED 0.57
Compound (SMILES): Cc1ccc(N2CCN(c3ccc(/C=N/Nc4ccc(S(N)(=O)=O)cc4)cc3)CC2)c(C)c1
InChIKey: SQXUZKQPTDIYDY-OVVQPSECSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as CO2 hydration preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye-based stopped-flow assay
Measurement: Ki = 1738.1 nM (pChEMBL 5.760000228881836)
Descriptors: MW 463.61, ALogP 3.72, HBA 6, HBD 2, PSA 91.03, QED 0.43
Compound (SMILES): NS(=O)(=O)c1ccc(O)c(NC(=O)Nc2ccc(Cl)cc2)c1
InChIKey: LJHAJNWTPVKHFW-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 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 = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 341.78, ALogP 2.34, HBA 4, HBD 4, PSA 121.52, QED 0.64
Compound (SMILES): Cc1ccc(-c2c(-c3cc(C(=O)O)ccn3)ncn2C)cc1
InChIKey: SKXLKYYCGCMBHU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 293.33, ALogP 3.16, HBA 4, HBD 1, PSA 68.01, QED 0.81
Compound (SMILES): CN(C/C=C/C=C/c1ccc(C(F)(F)F)cc1)Cc1ccc2c(c1)OCCO2.Cl
InChIKey: LPROHUCXSLIBNO-BJMABRHOSA-N
Target: 4,4'-diapophytoene desaturase (4,4'-diaponeurosporene-forming) (SINGLE PROTEIN), Staphylococcus aureus (strain Newman)
UniProt: O07855
Assay: Inhibition of CrtN in linezolid-resistant Staphylococcus aureus NRS271 assessed as reduction in staphyloxanthin levels after 48 hrs by spectrophotometric method-based pigment inhibition assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 389.42, ALogP 5.18, HBA 3, HBD 0, PSA 21.7, QED 0.64
Compound (SMILES): C#CCn1ccc2cc(NC(=O)N(CC)CC)ccc21
InChIKey: HYOYQHFZKJUMFE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butyrylthiocholine iodide as substrate pretreated for 10 mins followed by substrate addition and measured after 10 mins by Ellman's method
Measurement: IC50 = 3960 nM (pChEMBL 5.400000095367432)
Descriptors: MW 269.35, ALogP 3.15, HBA 2, HBD 1, PSA 37.27, QED 0.85
Compound (SMILES): Clc1ccc(-c2c(-c3cc(-c4nn[nH]n4)ccn3)ncn2CCc2ccccc2Cl)cc1
InChIKey: WGXLMGBZJXLXOA-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, and 5 μM ammonium iron(II) sulfate. Reaction product was 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 were 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 was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl 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 were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 462.34, ALogP 5.34, HBA 6, HBD 1, PSA 85.17, QED 0.37
Compound (SMILES): CCOc1cc(CN2CCC(c3ncc(-c4ccc(F)cc4)[nH]3)CC2)cc(OCC)c1-c1ccc(F)cc1
InChIKey: GOBNHYGEALNGCV-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Antagonist activity at mouse SSTR5 expressed in CHO-K1 cell membranes assessed as reduction in SST-28-induced inhibition of forskolin-stimulated cAMP accumulation by LANCE assay
Measurement: IC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 517.62, ALogP 7.2, HBA 4, HBD 1, PSA 50.38, QED 0.26
Compound (SMILES): CCOC(=O)c1cnc(OCC)n2nc(-c3ccco3)nc12
InChIKey: SWLCGYWFCAPFOH-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 302.29, ALogP 1.96, HBA 8, HBD 0, PSA 91.75, QED 0.67
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)C3)nc(-c3ccnc(C(F)(F)F)n3)n2)C1
InChIKey: VWUHSVAZJFWQPW-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 465.38, ALogP 4.55, HBA 7, HBD 2, PSA 88.51, QED 0.63
Compound (SMILES): Cc1nc(Nc2ccc(Cl)cc2)sc1C(=O)c1cnc(N)n1-c1ccc(F)cc1
InChIKey: PIZWNHKSSVITKB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at recombinant human A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 427.89, ALogP 4.99, HBA 7, HBD 2, PSA 85.83, QED 0.44
Compound (SMILES): Fc1cc(F)cc(Nc2nc(NC3CC(F)(F)C3)nc(-n3ccc(C(F)(F)F)n3)n2)c1
InChIKey: XSFFZJKIWXEYIL-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 447.32, ALogP 4.31, HBA 7, HBD 2, PSA 80.55, QED 0.57
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OC2CCCc3cc(Cl)ccc32)c1
InChIKey: MYEIDQDVSWLKKZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 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-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A 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 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 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 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 369.81, ALogP 4.08, HBA 5, HBD 1, PSA 77.24, QED 0.75
Compound (SMILES): C[C@@H](Nc1nc(NC2CCOC2)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: RWSYXAQFFAQAEC-RWANSRKNSA-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 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 394.4, ALogP 3.36, HBA 7, HBD 2, PSA 84.85, QED 0.78
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](Cc1ccc(S(=O)(=O)O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H]1CCc2c(F)cccc21
InChIKey: WOIZNLWOYISVQN-ZFIFVKQDSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from N-terminal His-tagged human recombinant XIAP BIR3 (253 to 347 residues) expressed in Escherichia coli BL21(DE3) Gold after 1 hr by DELFIA
Measurement: IC50 = 23.2 nM (pChEMBL 7.630000114440918)
Descriptors: MW 560.65, ALogP 1.5, HBA 6, HBD 4, PSA 144.91, QED 0.34
Compound (SMILES): N#Cc1cccc2c1CN(CCn1cnc(-c3cc(C(=O)O)ccn3)c1)C2
InChIKey: LAEIVQMOCJOJOW-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 359.39, ALogP 2.53, HBA 6, HBD 1, PSA 95.04, QED 0.75
Compound (SMILES): CCCS(=O)(=O)N(C)c1ccc2nc(-c3ccc(Cl)cc3)c(CN3CCN(C(C)=O)CC3)n2c1
InChIKey: PRINDMKXVIWHLA-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 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 504.06, ALogP 3.49, HBA 6, HBD 0, PSA 78.23, QED 0.49
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](Cc1cc(C)c(C(F)(F)F)cc1F)C(=O)N1CCC[C@H]1C(=O)N[C@@H]1CCc2c(F)cccc21
InChIKey: NTTJUNKJFQKLSG-RGWZMNCVSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from N-terminal His-tagged human recombinant XIAP BIR3 (253 to 347 residues) expressed in Escherichia coli BL21(DE3) Gold after 1 hr by DELFIA
Measurement: IC50 = 37.1 nM (pChEMBL 7.429999828338623)
Descriptors: MW 580.6, ALogP 3.72, HBA 4, HBD 3, PSA 90.54, QED 0.42
Compound (SMILES): CCCC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(=O)O)=C[C@@H]1O
InChIKey: QMDABYTUXUBWJL-MXMUJRTHSA-N
Target: Sialidase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WWR8
Assay: Inhibition of MBP-fused human NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 8400 nM (pChEMBL 5.079999923706055)
Descriptors: MW 319.31, ALogP -2.29, HBA 7, HBD 6, PSA 156.55, QED 0.31
Compound (SMILES): O=C(O)CC1COc2cc(OCCCOc3cccc(-c4ccccc4)c3)ccc21
InChIKey: NYHQSXAYPOAUNC-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 expressed in CHO cells assessed as increase in intracellular Ca2+ flux after 1 hr by Fluo4-AM dye based FLIPR assay
Measurement: EC50 = 2760 nM (pChEMBL 5.559999942779541)
Descriptors: MW 404.46, ALogP 5.15, HBA 4, HBD 1, PSA 64.99, QED 0.5
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2-c2ccc(Cl)c(O)c2)c1
InChIKey: KLXSSSNBZFSVGC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 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-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A 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 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 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 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 315.72, ALogP 2.99, HBA 5, HBD 2, PSA 88.24, QED 0.78