lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCc1noc(C(C)Nc2nccc(N3C(=O)OC[C@@H]3C(C)C)n2)n1
InChIKey: ZLPXCIWDUPDYDM-RRKGBCIJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: LC-MS Biochemical Assay: Mutant IDH1 R132H catalytic activity was monitored using the quantitative liquid chromatography/mass spectrometry (LC-MS) detection of 2-HG, a product of the NADPH-dependent alpha-KG reduction reaction.More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Costar, Cat. No. 781201) using a final reaction volume of 30 uL and the following assay buffer conditions: 50 mM HEPES pH 7.4, 10 mM MgCl2, 50 mM KCl, 1 mM DTT, 0.02% BSA, 5 uM NADPH and 100 uM alpha-KG.The final reaction mixture contained 3.3% DMSO and inhibitors with concentrations ranging 0.02-50 uM. The IDH1 enzyme was used at a final concentration of 0.25 nM. Following 45 minutes incubation, the reaction mixtures were quenched by the addition of 10 uL of 16% formic acid containing 800 nM of 5-carbon labeled 13C-2-HG). The protein was then precipitated by the addition of 2.5 volumes of acetonitrile followed by centrifugation (3000xg, 20 minutes).
Measurement: IC50 = 21616 nM (pChEMBL 4.670000076293945)
Descriptors: MW 346.39, ALogP 2.58, HBA 8, HBD 1, PSA 106.27, QED 0.85
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(C2CC2)no1
InChIKey: WJWKZWMICAWIME-TVKKRMFBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 4190 nM (pChEMBL 5.380000114440918)
Descriptors: MW 358.4, ALogP 2.89, HBA 8, HBD 1, PSA 106.27, QED 0.84
Compound (SMILES): CC(C)c1noc(C(C)Nc2nccc(N3C(=O)OC[C@@H]3C(C)C)n2)n1
InChIKey: LYSUZRSEBDIJBV-PIJUOVFKSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 360.42, ALogP 3.14, HBA 8, HBD 1, PSA 106.27, QED 0.84
Compound (SMILES): CCn1ccc(C(C)Nc2nccc(N3C(=O)OC[C@@H]3C(C)C)n2)n1
InChIKey: GYPWQVHWULXSMZ-TYZXPVIJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 344.42, ALogP 2.85, HBA 7, HBD 1, PSA 85.17, QED 0.87
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(-c2ccccc2)no1
InChIKey: FWKNLUIHTQDXKG-AWKYBWMHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 394.44, ALogP 3.68, HBA 8, HBD 1, PSA 106.27, QED 0.67
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1cnc2[nH]ccc2c1
InChIKey: MHOMYGMYJSCKJN-WPZCJLIBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 366.43, ALogP 3.51, HBA 6, HBD 2, PSA 96.03, QED 0.72
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc2ccccc2s1
InChIKey: HUSIHIHOMJMCJD-TYZXPVIJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 383.48, ALogP 4.24, HBA 7, HBD 1, PSA 80.24, QED 0.71
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1cc2ccccn2c1
InChIKey: AXOONVKWXWKGEX-FBMWCMRBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 526 nM (pChEMBL 6.28000020980835)
Descriptors: MW 365.44, ALogP 3.88, HBA 6, HBD 1, PSA 71.76, QED 0.74
Compound (SMILES): COc1ccccc1-c1noc(C(C)Nc2nccc(N3C(=O)OC[C@@H]3C(C)C)n2)n1
InChIKey: YKTYXHGGNOVFFG-AWKYBWMHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 424.46, ALogP 3.69, HBA 9, HBD 1, PSA 115.5, QED 0.61
Compound (SMILES): COc1cccc(-c2noc(C(C)Nc3nccc(N4C(=O)OC[C@@H]4C(C)C)n3)n2)c1
InChIKey: QOEHDCORKMZOHM-FQNRMIAFSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 224 nM (pChEMBL 6.650000095367432)
Descriptors: MW 424.46, ALogP 3.69, HBA 9, HBD 1, PSA 115.5, QED 0.61
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(-c2cccc(F)c2)no1
InChIKey: SWVNLHJTZWNLJF-WPZCJLIBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 412.43, ALogP 3.82, HBA 8, HBD 1, PSA 106.27, QED 0.65
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(C2CCCCC2)no1
InChIKey: XNDMAXVDBHXLAZ-AWKYBWMHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 400.48, ALogP 4.06, HBA 8, HBD 1, PSA 106.27, QED 0.77
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nnc(-c2ccc(F)cc2)o1
InChIKey: AUBGVCAXOQPLIS-WPZCJLIBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 412.43, ALogP 3.82, HBA 8, HBD 1, PSA 106.27, QED 0.65
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc2ccccc2o1
InChIKey: YGCUYQQAFXDMSW-TYZXPVIJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 309.5 nM (pChEMBL 6.510000228881836)
Descriptors: MW 367.41, ALogP 3.77, HBA 7, HBD 1, PSA 93.38, QED 0.73
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(-c2ccncc2)no1
InChIKey: RFTPUZQLBJSDNO-TYZXPVIJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 395.42, ALogP 3.08, HBA 9, HBD 1, PSA 119.16, QED 0.67
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(-c2ccccc2Cl)no1
InChIKey: JHJVPUJOBOLPSF-WPZCJLIBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 14800 nM (pChEMBL 4.829999923706055)
Descriptors: MW 428.88, ALogP 4.33, HBA 8, HBD 1, PSA 106.27, QED 0.62
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(-c2ccc(Cl)cc2)no1
InChIKey: PEEWKHRIJDGILX-WPZCJLIBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 2450 nM (pChEMBL 5.610000133514404)
Descriptors: MW 428.88, ALogP 4.33, HBA 8, HBD 1, PSA 106.27, QED 0.62
Compound (SMILES): CCn1nccc1C(C)Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1
InChIKey: KBBKNWCHENNLMP-TYZXPVIJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 344.42, ALogP 2.85, HBA 7, HBD 1, PSA 85.17, QED 0.87
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1cnc(-c2ccccc2)s1
InChIKey: IRGBHMIQDXZZDP-BZSJEYESSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 811 nM (pChEMBL 6.090000152587891)
Descriptors: MW 409.52, ALogP 4.75, HBA 7, HBD 1, PSA 80.24, QED 0.63
Compound (SMILES): Cc1ccccc1-c1noc(C(C)Nc2nccc(N3C(=O)OC[C@@H]3C(C)C)n2)n1
InChIKey: MQKIWEAHSLYCLV-BZSJEYESSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 5310 nM (pChEMBL 5.28000020980835)
Descriptors: MW 408.46, ALogP 3.99, HBA 8, HBD 1, PSA 106.27, QED 0.65
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1ccc(S(=O)(=O)N(C)C)cc1
InChIKey: QGCUGCUFLNMTOV-FBMWCMRBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 368.5 nM (pChEMBL 6.429999828338623)
Descriptors: MW 433.53, ALogP 2.88, HBA 7, HBD 1, PSA 104.73, QED 0.72
Compound (SMILES): COc1ccc(-c2noc(C(C)Nc3nccc(N4C(=O)OC[C@@H]4C(C)C)n3)n2)cc1
InChIKey: XKMULHOCWAMMBP-FQNRMIAFSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 113.5 nM (pChEMBL 6.949999809265137)
Descriptors: MW 424.46, ALogP 3.69, HBA 9, HBD 1, PSA 115.5, QED 0.61
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1nc(-c2ccc(F)cc2)no1
InChIKey: VXBCBCASQHFSAS-WPZCJLIBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 6115 nM (pChEMBL 5.210000038146973)
Descriptors: MW 412.43, ALogP 3.82, HBA 8, HBD 1, PSA 106.27, QED 0.65
Compound (SMILES): Cc1cc(-c2ccc(C(C)Nc3nccc(N4C(=O)OC[C@@H]4C(C)C)n3)nc2)ccc1F
InChIKey: HBHNBVQOMXUYKF-CAWMZFRYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 26.6 nM (pChEMBL 7.579999923706055)
Descriptors: MW 435.5, ALogP 5.14, HBA 6, HBD 1, PSA 80.24, QED 0.58
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1ncc(Oc2ccc(F)cc2)cn1
InChIKey: QZSFGXVFAIYNNF-XPKAQORNSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 438.46, ALogP 4.35, HBA 8, HBD 1, PSA 102.36, QED 0.58
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1ccc(Oc2ccc(F)cc2)cn1
InChIKey: SUSODDZMTBLOMI-YQYDADCPSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 5430 nM (pChEMBL 5.260000228881836)
Descriptors: MW 437.48, ALogP 4.96, HBA 7, HBD 1, PSA 89.47, QED 0.56
Compound (SMILES): CC(Nc1ncc(F)c(N2C(=O)OC(C)(C)[C@H]2c2ccccc2)n1)c1ccc(Oc2ccc(F)cc2)cn1
InChIKey: DAFGPZFSQINQHZ-FZYLFJGDSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 51.8 nM (pChEMBL 7.289999961853027)
Descriptors: MW 517.54, ALogP 6.59, HBA 7, HBD 1, PSA 89.47, QED 0.3
Compound (SMILES): CCCOc1ccc(C2C(=O)NC(=O)N2c2ccc3[nH]cnc3c2)cc1
InChIKey: GTFPAKYEYXNXOT-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Spectrophotometric Assay: This novel assay was used to determine the kinetic parameters for most of the QC substrates. QC activity was analyzed spectrophotometrically using a continuous method, that was derived by adapting a previous discontinuous assay (Bateman, R. C. J. 1989 J Neurosci Methods 30, 23-28) utilizing glutamate dehydrogenase as auxiliary enzyme. Samples consisted of the respective QC substrate, 0.3 mM NADH, 14 mM alpha-Ketoglutaric acid and 30 U/ml glutamate dehydrogenase in a final volume of 250 ul. Reactions were started by addition of QC and persued by monitoring of the decrease in absorbance at 340 nm for 8-15 min. The initial velocities were evaluated and the enzymatic activity was determined from a standard curve of ammonia under assay conditions. All samples were measured at 30 C., using either the SPECTRAFluor Plus or the Sunrise (both from TECAN) reader for microplates. Kinetic data was evaluated using GraFit software.
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 350.38, ALogP 3.15, HBA 4, HBD 2, PSA 87.32, QED 0.69
Compound (SMILES): CS(=O)(=O)C(C(=O)NCCS(N)(=O)=O)c1nc2cc(-c3ccnc(F)c3)ccc2s1
InChIKey: HMXSAQYEGHMUAZ-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 472.55, ALogP 0.99, HBA 8, HBD 2, PSA 149.18, QED 0.49
Compound (SMILES): CS(=O)(=O)C(C(=O)NCCS(N)(=O)=O)c1nc2ccc(-c3ccc(C(=O)N4CCOCC4)cc3)cc2s1
InChIKey: JEAMIOQTBZKUMG-UHFFFAOYSA-N
Target: Hepatic triacylglycerol lipase (SINGLE PROTEIN), Homo sapiens
UniProt: P11150
Assay: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 566.68, ALogP 0.93, HBA 9, HBD 2, PSA 165.83, QED 0.41
Compound (SMILES): NS(=O)(=O)CCNC(=O)C(c1nc2ccc(-c3ccc(C(=O)N4CCOCC4)cc3)cc2s1)S(=O)(=O)CC1CC1
InChIKey: HJHZPDCHBCRLEZ-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 606.75, ALogP 1.71, HBA 9, HBD 2, PSA 165.83, QED 0.35
Compound (SMILES): COCCNC(=O)c1ccc(-c2ccc3nc(C(C(=O)NCCS(N)(=O)=O)S(=O)(=O)Cc4ccc(OC(F)(F)F)cc4)sc3c2)cc1
InChIKey: OEXUPJCONPLVRQ-UHFFFAOYSA-N
Target: Hepatic triacylglycerol lipase (SINGLE PROTEIN), Homo sapiens
UniProt: P11150
Assay: Biological Assay: Endothelial lipase (EL) and hepatic lipase (HL) activities were measured using a fluorescent substrate, A10070, (Invitrogen, CA) doped into an artificial vesicle containing DMPG (Avanti Polar Lipids) as the excipient. Vesicles were prepared by combining 571 uL of 29 mM DMPG in a 1:1 mixture of MeOH and CHCl3 with 2000 uL of 1 mM A10070 in a 1:1 mixture of MeOH and CHCl3. The mixture was dried under nitrogen in multiple vials then resuspended in 20 mL total volume of 50 mM HEPES pH 8.0 buffer containing 50 mM NaCl and 0.2 mM EDTA. The sample was allowed to sit at room temperature for 15 min and then was sonicated 3x4 mins on ice with a Branson Sonicator using duty cycle 1. This preparation provides vesicles with a mole fraction of 0.11 for the FRET substrate.The enzymatic assay was measured using 384-well white Optiplates. Each well contained 20 uL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 0.25 uL of a DMSO solution containing a compound.
Measurement: IC50 = 306.1 nM (pChEMBL 6.510000228881836)
Descriptors: MW 714.77, ALogP 3.3, HBA 10, HBD 3, PSA 183.85, QED 0.17
Compound (SMILES): Cn1nccc1-c1cc(C(F)(F)F)ccc1-c1cccc2cc(S(=O)(=O)Nc3ncns3)ccc12
InChIKey: NEGWWOJFNIDTET-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells assessed as inhibition of sodium current at holding potential of -125 mV measured for 3 to 5 mins by whole cell voltage clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 515.54, ALogP 5.58, HBA 7, HBD 1, PSA 89.77, QED 0.33
Compound (SMILES): O=C([C@H]1CC1c1ccccc1)N1CCN(C2CCC2)CC1
InChIKey: GZEMSLIEGKLMPR-DJNXLDHESA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 3.41 nM (pChEMBL 8.470000267028809)
Descriptors: MW 284.4, ALogP 2.49, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): CC(C)N1CCN(C(=O)[C@H]2CC2c2ccc(F)cc2)CC1
InChIKey: UXUFOKSCQDHIIA-LYKKTTPLSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: SPA Assay: The H3 binding assay was/can be used to evaluate the ability of at least one compound in accordance with formula I, Ia, Ib, and/or Ic to inhibit [3H]-N-α-methylhistamine binding to CHO-K1 membranes expressing human histamine H3 receptors (full-length H3, the most prevalent brain isoform 445). In 200 μl 96-well SPA format, human H3 membranes (12.5 μg protein/well) and 1.4 nM [3H]-N-α-methylhistamine were/can be incubated with at least one compound in accordance with formula I, Ia, Ib, and/or Ic for 1.5 hrs to determine percent effect with respect to total (1% DMSO) and non-specific binding (10 μM imetit). Reproducibility of the assay is such that IC50 curves can be generated in singlicate.
Measurement: IC50 = 1630 nM (pChEMBL 5.789999961853027)
Descriptors: MW 290.38, ALogP 2.48, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): O=C([C@H]1CC1c1ccc(Br)cc1)N1CCN(C2CCC2)CC1
InChIKey: QXNSPQZOLIPIJZ-DJNXLDHESA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 6.813 nM (pChEMBL 8.170000076293945)
Descriptors: MW 363.3, ALogP 3.25, HBA 2, HBD 0, PSA 23.55, QED 0.82
Compound (SMILES): N#Cc1ccc(C2C[C@@H]2C(=O)N2CCN(C3CCC3)CC2)cc1
InChIKey: NXLUQWIKRBZQJH-ZVAWYAOSSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: SPA Assay: The H3 binding assay was/can be used to evaluate the ability of at least one compound in accordance with formula I, Ia, Ib, and/or Ic to inhibit [3H]-N-α-methylhistamine binding to CHO-K1 membranes expressing human histamine H3 receptors (full-length H3, the most prevalent brain isoform 445). In 200 μl 96-well SPA format, human H3 membranes (12.5 μg protein/well) and 1.4 nM [3H]-N-α-methylhistamine were/can be incubated with at least one compound in accordance with formula I, Ia, Ib, and/or Ic for 1.5 hrs to determine percent effect with respect to total (1% DMSO) and non-specific binding (10 μM imetit). Reproducibility of the assay is such that IC50 curves can be generated in singlicate.
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 309.41, ALogP 2.36, HBA 3, HBD 0, PSA 47.34, QED 0.86
Compound (SMILES): CC(C)N1CCN(C(=O)C2CC2c2ccccc2)CC1
InChIKey: FHGXMOHTTKRNRT-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Guanosine 5'-O-(3-[35S]thio)triphosphate [GTP gamma S] Binding Assay: A GTP gamma S binding assay can be used to investigate antagonist properties of compounds in CHO cells (Chinese Hamster Ovary) transfected with human Histamine H3 receptor (hH3R). Membranes from CHO cells expressing hH3R (10 ug/well) are diluted in GTP gamma S assay buffer (20 mM Hepes, 10 mM MgCl2, 100 mM NaCl, pH 7.4) and preincubated with saponine (3 ug/ml), GDP (10 uM) and PVT-WGA SPA beads (125 ug/well) (Amersham) for 30 minutes. To determine antagonist activity, (R)-methyl histamine (30 nM) is added in 96 well SPA plate with [35S]GTP gamma S (0.2 nM) and various concentration of H3R antagonists. The GTP gamma S binding assay is started with addition of the mixture membrane/saponine/GDP and incubated for 90 minutes at room temperature. The amount of bound [35S]GTP gamma S is determined by using the MicroBeta Trilux counter (PerkinElmer). The percentage of [35S]GTP gamma S bound in each sample is calculated as a percentage of that bound control sample.
Measurement: IC50 = 3534 nM (pChEMBL 5.449999809265137)
Descriptors: MW 272.39, ALogP 2.34, HBA 2, HBD 0, PSA 23.55, QED 0.84