lovingscience/chembl-v37-raw-activities huggingface dataset:
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: 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 = 7595 nM (pChEMBL 5.119999885559082)
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: 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 = 909 nM (pChEMBL 6.039999961853027)
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(-c2cccnc2)no1
InChIKey: FGBFPYWBLNXTGQ-TYZXPVIJSA-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 = 1229 nM (pChEMBL 5.909999847412109)
Descriptors: MW 395.42, ALogP 3.08, HBA 9, HBD 1, PSA 119.16, QED 0.67
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: 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 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 344.42, ALogP 2.85, HBA 7, HBD 1, PSA 85.17, QED 0.87
Compound (SMILES): Cc1cccc(-c2noc(C(C)Nc3nccc(N4C(=O)OC[C@@H]4C(C)C)n3)n2)c1
InChIKey: GOBJPRCTHVAYDE-BZSJEYESSA-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 = 133 nM (pChEMBL 6.880000114440918)
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)c1cnc(-c2ccccc2)s1
InChIKey: IRGBHMIQDXZZDP-BZSJEYESSA-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 = 568 nM (pChEMBL 6.25)
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: 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 = 6675 nM (pChEMBL 5.179999828338623)
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: 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 = 291 nM (pChEMBL 6.539999961853027)
Descriptors: MW 433.53, ALogP 2.88, HBA 7, HBD 1, PSA 104.73, QED 0.72
Compound (SMILES): CC(Nc1nccc(N2C(=O)OC[C@@H]2C(C)C)n1)c1cscn1
InChIKey: ZRZHLITULPSHHK-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 = 2935 nM (pChEMBL 5.53000020980835)
Descriptors: MW 333.42, ALogP 3.09, HBA 7, HBD 1, PSA 80.24, QED 0.91
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: 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 = 125 nM (pChEMBL 6.900000095367432)
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: 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 = 4229 nM (pChEMBL 5.369999885559082)
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)c1noc(-c2ccc(Cl)cc2)n1
InChIKey: VNCZODINPSDRIC-WPZCJLIBSA-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 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 428.88, ALogP 4.33, HBA 8, HBD 1, PSA 106.27, QED 0.62
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: 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 = 40 nM (pChEMBL 7.400000095367432)
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: 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 = 80 nM (pChEMBL 7.099999904632568)
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: 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 = 34 nM (pChEMBL 7.46999979019165)
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: 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 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 517.54, ALogP 6.59, HBA 7, HBD 1, PSA 89.47, QED 0.3
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2cnc(Oc3ccc(F)cc3)cn2)n1
InChIKey: UCHDSSAFUHZSQS-KBXCAEBGSA-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 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 438.46, ALogP 4.35, HBA 8, HBD 1, PSA 102.36, QED 0.58
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1ccc2ccn(Cc3ccccc3)c2c1
InChIKey: XELVJQJHDQVRLT-AOEKMSOUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 421.5, ALogP 5.65, HBA 4, HBD 1, PSA 59.3, QED 0.3
Compound (SMILES): CS(=O)(=O)n1ccc2ccc(/C=C/C(=O)CC(=O)/C=C/c3ccc(O)cc3)cc21
InChIKey: UCVVXGHXXUPIKF-YOYBCKCWSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 409.46, ALogP 3.41, HBA 6, HBD 1, PSA 93.44, QED 0.48
Compound (SMILES): CC(C)(C)[Si](C)(C)OCc1ccccc1/C=C/C(=O)CC(=O)/C=C/c1ccc(O)cc1
InChIKey: DUBKTNGMEJDGSM-UNZYHPAISA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 436.62
Compound (SMILES): CCN(CC)c1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)cc2)c(OCc2ccccc2)c1
InChIKey: FLVVJCHITSHYIB-IJNKXORISA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 469.58, ALogP 6.07, HBA 5, HBD 1, PSA 66.84, QED 0.26
Compound (SMILES): N[C@@H](Cc1ccccc1)C(=O)Nc1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)cc2)cc1
InChIKey: KZIYBPDIYZXERL-SVBMQFAGSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 454.53, ALogP 4.16, HBA 5, HBD 3, PSA 109.49, QED 0.31
Compound (SMILES): N[C@H](Cc1ccccc1)C(=O)Nc1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)cc2)cc1
InChIKey: KZIYBPDIYZXERL-IETLPPTJSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 454.53, ALogP 4.16, HBA 5, HBD 3, PSA 109.49, QED 0.31
Compound (SMILES): CCN(CC)c1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)cc2)c(OCC=C(C)C)c1
InChIKey: FBTGLKCDIHTKIU-XGGJEREUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 447.58, ALogP 5.84, HBA 5, HBD 1, PSA 66.84, QED 0.25
Compound (SMILES): CCN(CC)c1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)cc2)c(OC(C)C)c1
InChIKey: QRAQCLBRTICTBY-XGGJEREUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 421.54, ALogP 5.28, HBA 5, HBD 1, PSA 66.84, QED 0.39
Compound (SMILES): COCOc1ccc(OC)cc1/C=C/C(=O)CC(=O)/C=C/c1cc(OC)ccc1O
InChIKey: IECWIPLKGWXFPW-YDFGWWAZSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 412.44, ALogP 3.65, HBA 7, HBD 1, PSA 91.29, QED 0.34
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1c[nH]c2cccc([N+](=O)[O-])c12
InChIKey: XXBBRVQTZYXDGE-JMQWPVDRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 376.37, ALogP 4.04, HBA 5, HBD 2, PSA 113.3, QED 0.28
Compound (SMILES): COc1ccc(/C=C/C(=O)CC(=O)/C=C/c2c[nH]c3cccc([N+](=O)[O-])c23)cc1O
InChIKey: TXBZBYOJNYBQIT-OCIXRKKMSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 406.39, ALogP 4.05, HBA 6, HBD 2, PSA 122.53, QED 0.25
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1cccc(Br)c1
InChIKey: FOLHNAYHMDRVKR-JMQWPVDRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 371.23, ALogP 4.41, HBA 3, HBD 1, PSA 54.37, QED 0.6
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1cc(Cl)ccc1[N+](=O)[O-]
InChIKey: NXJZQHFOVXHXDQ-BQYBEJQRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 371.78, ALogP 4.21, HBA 5, HBD 1, PSA 97.51, QED 0.34
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1ccccc1C(F)(F)F
InChIKey: BMPYEAVRKUHLDI-MKICQXMISA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 360.33, ALogP 4.67, HBA 3, HBD 1, PSA 54.37, QED 0.6
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1cc(F)cc(F)c1
InChIKey: CZVHQAOQTCONCU-FCXRPNKRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 328.31, ALogP 3.93, HBA 3, HBD 1, PSA 54.37, QED 0.65
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1ccccc1-c1ccccc1
InChIKey: MFOGQDREEHBOAT-UNZYHPAISA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 368.43, ALogP 5.31, HBA 3, HBD 1, PSA 54.37, QED 0.45
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1cc(C(F)(F)F)ccc1F
InChIKey: KWXARCJORAWAAU-BQYBEJQRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 378.32, ALogP 4.81, HBA 3, HBD 1, PSA 54.37, QED 0.45
Compound (SMILES): CCCN(CCC)C(=O)c1cccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)cc2)c1
InChIKey: WEKICTWJQJVXDX-WFYKWJGLSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 419.52, ALogP 4.91, HBA 4, HBD 1, PSA 74.68, QED 0.41
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1cc(OCc2ccccc2)ccc1[N+](=O)[O-]
InChIKey: KWNUURPTZKKESN-QHKWOANTSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 443.46, ALogP 5.13, HBA 6, HBD 1, PSA 106.74, QED 0.2
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)CC(=O)/C=C/c1ccccc1[N+](=O)[O-]
InChIKey: AFPZPCPFQGQHQS-MKICQXMISA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 337.33, ALogP 3.56, HBA 5, HBD 1, PSA 97.51, QED 0.36
Compound (SMILES): COC(=O)c1ccccc1/C=C/C(=O)CC(=O)/C=C/c1ccc(O)cc1
InChIKey: KFJLAXZSEQEHQY-QHKWOANTSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Enzyme Inhibition Assay: Compounds were dissolved in dimethylsulfoxide (DMSO), and further diluted in 0.1 M sodium acetate buffer (with 150 mM sodium chloride, pH 4.5). The solution with no compound was used as a negative control. Then, 100 Î¼L of these solutions (compound concentration: 3 uM), 1 Î¼L of recombinant human Î²-secretase (rhBACE-1, R&D), and 5 uL of the fluorescent substrate peptide were mixed in a black 96-well plate (Nunc). After mixtures were incubated in the dark at 37 C. for 2 hr, the fluorescence intensities of the mixtures were measured by fluorescence microplate reader (Wallac) at 540 nm for excitation and at 590 nm for emission. The inhibition ratio was calculated as a percentage of the negative control. The sequence of the peptide was Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Lys-Arg, and labeled with fluorescent donor (Cy3) at Ser-1 and with quencher (Cy5Q) at Lys-9, respectively (Invitrogen).
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 350.37, ALogP 3.43, HBA 5, HBD 1, PSA 80.67, QED 0.47