lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N[C@@H]3CCCC[C@H]3O)c(F)c2)n1
InChIKey: SKCUYSWGBYHMAZ-LWILDLIXSA-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 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 485.56, ALogP 3.8, HBA 7, HBD 3, PSA 116.68, QED 0.55
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N(C)C3CCOCC3)c(F)c2)n1
InChIKey: MQGKLBGKZOXEHX-HRAATJIYSA-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 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 485.56, ALogP 4.02, HBA 7, HBD 1, PSA 96.89, QED 0.63
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N(C)C)c(F)c2)n1
InChIKey: IOWDXECVTAWPTB-SUMWQHHRSA-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 = 741 nM (pChEMBL 6.130000114440918)
Descriptors: MW 415.47, ALogP 3.47, HBA 6, HBD 1, PSA 87.66, QED 0.78
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N3CCOCC3)c(F)c2)n1
InChIKey: JWNMZZVXYJHQDA-HNAYVOBHSA-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 = 715 nM (pChEMBL 6.150000095367432)
Descriptors: MW 457.51, ALogP 3.24, HBA 7, HBD 1, PSA 96.89, QED 0.71
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N3CCOC[C@H]3C)c(F)c2)n1
InChIKey: RPNJRAMKFDXSBB-GQIGUUNPSA-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 = 265 nM (pChEMBL 6.579999923706055)
Descriptors: MW 471.53, ALogP 3.63, HBA 7, HBD 1, PSA 96.89, QED 0.69
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N3CCC(O)CC3)c(F)c2)n1
InChIKey: YKFCLMUVRYKUQT-MGPUTAFESA-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 = 729 nM (pChEMBL 6.139999866485596)
Descriptors: MW 471.53, ALogP 3.37, HBA 7, HBD 2, PSA 107.89, QED 0.67
Compound (SMILES): COC1CCN(C(=O)c2ccc([C@H](C)Nc3nccc(N4C(=O)OC[C@@H]4C(C)C)n3)cc2F)CC1
InChIKey: LNBVDQRNYOIMFW-HRAATJIYSA-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 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 485.56, ALogP 4.02, HBA 7, HBD 1, PSA 96.89, QED 0.63
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N3CCC(F)CC3)c(F)c2)n1
InChIKey: SPMOACLZJLYUCA-MGPUTAFESA-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 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 473.52, ALogP 4.34, HBA 6, HBD 1, PSA 87.66, QED 0.67
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N3CCC[C@@H](O)C3)c(F)c2)n1
InChIKey: YUYUOANRNPPGPS-XAUMDUMWSA-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 = 336 nM (pChEMBL 6.46999979019165)
Descriptors: MW 471.53, ALogP 3.37, HBA 7, HBD 2, PSA 107.89, QED 0.67
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(C(=O)N3CCCC3)c(F)c2)n1
InChIKey: ZLWOPZCLRNPVAU-HNAYVOBHSA-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 = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 441.51, ALogP 4.01, HBA 6, HBD 1, PSA 87.66, QED 0.73
Compound (SMILES): CCCc1noc([C@H](C)Nc2nccc(N3C(=O)OC[C@@H]3C(C)C)n2)n1
InChIKey: BURWGDGQWDXWKN-NWDGAFQWSA-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 = 3010 nM (pChEMBL 5.519999980926514)
Descriptors: MW 360.42, ALogP 2.97, HBA 8, HBD 1, PSA 106.27, QED 0.8
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@H](C)c2cnc(Oc3ccc(F)cc3)cn2)n1
InChIKey: UCHDSSAFUHZSQS-RDTXWAMCSA-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 = 14500 nM (pChEMBL 4.840000152587891)
Descriptors: MW 438.46, ALogP 4.35, HBA 8, HBD 1, PSA 102.36, QED 0.58
Compound (SMILES): CCCc1noc([C@@H](C)Nc2nccc(N3C(=O)OC[C@@H]3C(C)C)n2)n1
InChIKey: BURWGDGQWDXWKN-VXGBXAGGSA-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 2.97, HBA 8, HBD 1, PSA 106.27, QED 0.8
Compound (SMILES): CC(C)c1cccc(-c2nccnc2C2CN(C(=O)c3nc4ccccc4[nH]3)C2)c1
InChIKey: UDZVGFIJADGXMY-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: IMAP TR-FRET assay: Enzyme Activity. An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 uL of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 uL of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).Enzyme Inhibition. To check the inhibition profile, 5 uL of serial diluted compounds were incubated with 5 uL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.).
Measurement: IC50 = 35.2 nM (pChEMBL 7.449999809265137)
Descriptors: MW 397.48, ALogP 4.38, HBA 4, HBD 1, PSA 74.77, QED 0.55
Compound (SMILES): COc1cc(-c2nccnc2C2CN(C(=O)c3nc4ccccc4[nH]3)C2)ccc1F
InChIKey: JXJOUSFJPXKUJH-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: MPDE10A7 Enzyme Activity: An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 L of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 L of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.). Enzyme Inhibition. To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 L of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer.
Measurement: IC50 = 42.4 nM (pChEMBL 7.369999885559082)
Descriptors: MW 403.42, ALogP 3.41, HBA 5, HBD 1, PSA 84, QED 0.56
Compound (SMILES): CC(C)(O)C1CCN(c2nccnc2C2CN(C(=O)c3nc4ccccc4[nH]3)C2)CC1
InChIKey: WBIYEERSZGTFEC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: MPDE10A7 Enzyme Activity: An IMAP TR-FRET assay was used to analyze the enzyme activity (Molecular Devices Corp., Sunnyvale Calif.). 5 L of serial diluted PDE10A (BPS Bioscience, San Diego, Calif.) or tissue homogenate was incubated with equal volumes of diluted fluorescein labeled cAMP or cGMP for 60 min in 384-well polystyrene assay plates (Corning, Corning, N.Y.) at room temperature. After incubation, the reaction was stopped by adding 60 L of diluted binding reagents and was incubated for 3 hours to overnight at room temperature. The plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.). Enzyme Inhibition. To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 L of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer.
Measurement: IC50 = 56.3 nM (pChEMBL 7.25)
Descriptors: MW 420.52, ALogP 2.58, HBA 6, HBD 2, PSA 98.24, QED 0.67
Compound (SMILES): CN1C(=O)NCc2c(NC(=O)N[C@@H]3CC(C)(C(F)F)Oc4cc(Cl)ccc43)cccc21
InChIKey: DZXQXVMNKBRKOR-RBFZIWAESA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Activation Assay: The cDNA for human TRPV1 (hTRPV1) was isolated by reverse transcriptase-polymerase chain reaction (RT-PCR) from human small intestine poly A+ RNA supplied by Clontech (Palo Alto, Calif.) using primers designed surrounding the initiation and termination codons identical to the published sequences (Hayes et al. Pain 2000, 88, 205-215). The resulting cDNA PCR products were subcloned into pCIneo mammalian expression vector (Promega) and fully sequenced using fluorescent dye-terminator reagents (Prism, PerkinElmer Applied Biosystems Division) and a PerkinElmer Applied Biosystems Model 373 DNA sequencer or Model 310 genetic analyzer. Expression plasmids encoding the hTRPV1 cDNA were transfected into HEK293 cells using Lipofectamine. Forty-eight hours after transfection, the neomycin-resistant cells were selected with growth medium containing 800 ug/mL Geneticin (Life Technologies, formerly Gibco BRL). Surviving individual colonies were isolated and screened for TRPV1 activity.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 450.87, ALogP 4.67, HBA 3, HBD 3, PSA 82.7, QED 0.64
Compound (SMILES): CN(C)c1ccc2cc(C(=O)N[C@@H](CCCNC(=N)CCl)C(=O)NCc3ccccc3)ccc2c1
InChIKey: LJJCYRVBDASIDX-DEOSSOPVSA-N
Target: Protein-arginine deiminase type-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM07
Assay: Inhibition of PAD4 (unknown origin)
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 494.04, ALogP 3.91, HBA 4, HBD 4, PSA 97.32, QED 0.14
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cnn(C4CCNCC4)c3)n2)ccc1OC1CCOCC1
InChIKey: MLQSFEZKSQONMK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 445.53, ALogP 3.44, HBA 9, HBD 2, PSA 109.91, QED 0.59
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cc(C(=O)O)ccn3)c2)ccc1OC1CCOCC1
InChIKey: KPJNILHFVBUXEY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 416.44, ALogP 4.01, HBA 7, HBD 2, PSA 117.36, QED 0.62
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3ncc(C4CCNCC4)cn3)c2)ccc1OC1CCOCC1
InChIKey: UDLCUPNAFTWKLG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 456.55, ALogP 4.18, HBA 8, HBD 2, PSA 104.98, QED 0.57
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cnn(C[C@H]4C[C@@H]4CO)c3)n2)ccc1OC1CCOCC1
InChIKey: MQZYHFYFOXLRBV-RTBURBONSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 446.51, ALogP 3.14, HBA 9, HBD 2, PSA 118.11, QED 0.54
Compound (SMILES): Cn1nc(Nc2nccc(-c3ccc(OC4CCOCC4)c(C#N)c3)n2)ccc1=O
InChIKey: ZUDLFDOJAKMMDT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 404.43, ALogP 2.41, HBA 9, HBD 1, PSA 114.95, QED 0.69
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3ccc(=O)[nH]n3)n2)ccc1OC1CCOCC1
InChIKey: FNKYBCOJEZQTSI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 390.4, ALogP 2.4, HBA 8, HBD 2, PSA 125.81, QED 0.68
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cc(CO)ccn3)n2)ccc1OC1CCOCC1
InChIKey: FQMQKRIYLONZDU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 403.44, ALogP 3.2, HBA 8, HBD 2, PSA 113.18, QED 0.65
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3ccc(C4CCNCC4)nn3)c2)ccc1OC1CCOCC1
InChIKey: HNBPCYSNJZUPBY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 456.55, ALogP 4.18, HBA 8, HBD 2, PSA 104.98, QED 0.57
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cnc(C4CCNCC4)cn3)c2)ccc1OC1CCOCC1
InChIKey: TVLWSLIAVPDZCA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 456.55, ALogP 4.18, HBA 8, HBD 2, PSA 104.98, QED 0.57
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cnn([C@H]4CC[C@@H](O)CC4)c3)n2)ccc1OC1CCOCC1
InChIKey: ZXXUISVZQNQVSN-OYRHEFFESA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 460.54, ALogP 3.99, HBA 9, HBD 2, PSA 118.11, QED 0.57
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cc(C4CCNCC4)ccn3)c2)ccc1OC1CCOCC1
InChIKey: LYMQARVHTYDQHO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 455.56, ALogP 4.78, HBA 7, HBD 2, PSA 92.09, QED 0.55
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cnn(CCO)c3)n2)ccc1OC1CCOCC1
InChIKey: NKOHMDYLNLLENR-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Flashplate Assay: 1 nM IKKe, 800 nM biotinylated IkBalpha(19-42) peptide (Biotin-C6-C6-GLKKERLLDDRHDSGLDSMKDEE) and 10 Î¼M ATP (spiked with 0.3 uCi of 33P-ATP/well) are incubated at 30 C. for 2 hours in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM dithiothreitol, 0.02% of Brij35, 0.1% of BSA, 0.1% of BioStab, pH 7.5) with or without test compound. The reaction is stopped using 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 Î¼l of 0.9% sodium chloride solution. Non-specific reaction is determined in the presence of 3 uM MSC2119074 (BX-795). The radioactivity is measured using a Topcount (PerkinElmer).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 406.45, ALogP 2.51, HBA 9, HBD 2, PSA 118.11, QED 0.61
Compound (SMILES): COc1nc(Nc2nccc(-c3ccc(OC4CCOCC4)c(C#N)c3)n2)ccc1C1=CCNCC1
InChIKey: SLCMXEFQPWEZOR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 484.56, ALogP 4.1, HBA 9, HBD 2, PSA 114.21, QED 0.51
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cc(CN)ccn3)c2)ccc1OC1CCOCC1
InChIKey: TUIAFUOZECMRAZ-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Flashplate Assay: 1 nM IKKe, 800 nM biotinylated IkBalpha(19-42) peptide (Biotin-C6-C6-GLKKERLLDDRHDSGLDSMKDEE) and 10 Î¼M ATP (spiked with 0.3 uCi of 33P-ATP/well) are incubated at 30 C. for 2 hours in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM dithiothreitol, 0.02% of Brij35, 0.1% of BSA, 0.1% of BioStab, pH 7.5) with or without test compound. The reaction is stopped using 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 Î¼l of 0.9% sodium chloride solution. Non-specific reaction is determined in the presence of 3 uM MSC2119074 (BX-795). The radioactivity is measured using a Topcount (PerkinElmer).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 401.47, ALogP 3.78, HBA 7, HBD 2, PSA 106.08, QED 0.65
Compound (SMILES): CN1CCC(c2ccnc(Nc3cc(-c4ccc(OC5CCOCC5)c(C#N)c4)ccn3)c2)CC1
InChIKey: UONSKTNQTWRUCS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 469.59, ALogP 5.13, HBA 7, HBD 1, PSA 83.3, QED 0.54
Compound (SMILES): N#Cc1cc(-c2ccnc(Nc3cnn(CCO)c3)c2)ccc1OC1CCOCC1
InChIKey: HPYDIJUSTZXNRN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Flashplate Assay: The kinase assay is performed as 384-well flashplate assay (for example for Topcount measurement).0.6 nM TANK binding kinase (TBK1), 800 nM biotinylated MELK-derived peptide (Biotin-Ah-Ah-AKPKGNKDYHLQTCCGSLAYRRR) and 10 uM ATP (spiked with 0.25 uCi of 33P-ATP/well) are incubated at 30 C. for 120 min in a total volume of 50 ul (10 mM MOPS, 10 mM Mg acetate, 0.1 mM EGTA, 1 mM DTT, 0.02% of Brij35, 0.1% of BSA, pH 7.5) with or without test compound. The reaction is stopped with 25 ul of 200 mM EDTA. After 30 min at room temperature, the liquid is removed, and each well is washed three times with 100 ul of 0.9% sodium chloride solution. Non-specific reaction is measured in the presence of 100 nM staurosporine. The radioactivity is measured in a Topcount (PerkinElmer).
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 405.46, ALogP 3.11, HBA 8, HBD 2, PSA 105.22, QED 0.62
Compound (SMILES): CC1(O)CN(C(=O)c2ccc(-c3ccc4nc(C(C(=O)NCCS(N)(=O)=O)S(=O)(=O)Cc5ccc(C(F)(F)F)cc5)sc4c3)cc2)C1
InChIKey: FKJUBJUFAXWLKR-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 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 710.78, ALogP 3.25, HBA 9, HBD 3, PSA 176.83, QED 0.22
Compound (SMILES): CC1(O)CN(C(=O)c2ccc(-c3ccc4nc(C(C(=O)NCCS(N)(=O)=O)S(=O)(=O)Cc5ccc(OC(F)(F)F)cc5)sc4c3)cc2)C1
InChIKey: WCBVGJZCCYWJBP-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 = 81.7 nM (pChEMBL 7.090000152587891)
Descriptors: MW 726.78, ALogP 3.13, HBA 10, HBD 3, PSA 186.06, QED 0.21
Compound (SMILES): NS(=O)(=O)CCNC(=O)C(c1nc2ccc(-c3ccc(C(=O)N4CCC(F)(F)C4)cc3)cc2s1)S(=O)(=O)Cc1ccc(OC(F)(F)F)cc1
InChIKey: BZFPGJPTTUEYCM-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 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 746.76, ALogP 4.4, HBA 9, HBD 2, PSA 165.83, QED 0.21
Compound (SMILES): Cc1cc2nc(C(C(=O)NCCS(N)(=O)=O)S(=O)(=O)Cc3ccccc3)sc2cc1-c1ccc(C(=O)O)cc1
InChIKey: FGYILSKPCFDTDS-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 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 587.7, ALogP 3.03, HBA 8, HBD 3, PSA 173.59, QED 0.25
Compound (SMILES): Cc1cc2nc(C(C(=O)NCCS(N)(=O)=O)S(C)(=O)=O)sc2cc1-c1ccc(C(=O)O)cc1
InChIKey: GUILYDHMFXRLNK-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 = 201.4 nM (pChEMBL 6.699999809265137)
Descriptors: MW 511.6, ALogP 1.46, HBA 8, HBD 3, PSA 173.59, QED 0.41