lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(-c2cn[nH]c2)cn2c(-c3ccccc3)c(-c3ccc(C4(N)CCC4)cc3)nc12
InChIKey: WTRPETLHOOKVDX-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCl pH 7.5, 5 mM MgCl2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C. to allow prebinding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 uM=>final conc. in the 5 ul assay volume is 10 uM) and substrate (1.67 uM=>final conc. in the 5 ul assay volume is 1 uM) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 435.53, ALogP 5.4, HBA 5, HBD 2, PSA 81.23, QED 0.39
Compound (SMILES): Cc1cccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n12
InChIKey: AQQGZTUNRJVZAQ-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCl pH 7.5, 5 mM MgCl2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C. to allow prebinding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 uM=>final conc. in the 5 ul assay volume is 10 uM) and substrate (1.67 uM=>final conc. in the 5 ul assay volume is 1 uM) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 1505 nM (pChEMBL 5.820000171661377)
Descriptors: MW 353.47, ALogP 5.31, HBA 3, HBD 1, PSA 43.32, QED 0.54
Compound (SMILES): N#Cc1cc(Cl)c2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2c1
InChIKey: VHGGDRGBYFHHAS-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCl pH 7.5, 5 mM MgCl2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22 C. to allow prebinding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 ul of a solution of adenosine-tri-phosphate (ATP, 16.7 uM=>final conc. in the 5 ul assay volume is 10 uM) and substrate (1.67 uM=>final conc. in the 5 ul assay volume is 1 uM) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22 C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot.
Measurement: IC50 = 141 nM (pChEMBL 6.849999904632568)
Descriptors: MW 398.9, ALogP 5.53, HBA 4, HBD 1, PSA 67.11, QED 0.49
Compound (SMILES): Cn1cc(C(N)=O)c2c1-c1nc(N)ncc1CC2
InChIKey: UXWNPSLXAXDXKK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 243.27, ALogP 0.26, HBA 5, HBD 2, PSA 99.82, QED 0.75
Compound (SMILES): NC(=O)c1c(-c2ccccc2)[nH]c2c1ccc1cnc(N)nc12
InChIKey: BWJORBLWBGOLQL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 303.32, ALogP 2.46, HBA 4, HBD 3, PSA 110.68, QED 0.53
Compound (SMILES): Cn1c2c(c(C(N)=O)c1-c1ccccc1)CCc1cnc(N)nc1-2
InChIKey: KVWLHWMGSYRLAU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 319.37, ALogP 1.93, HBA 5, HBD 2, PSA 99.82, QED 0.75
Compound (SMILES): Cn1c(-c2ccccc2)c(C(N)=O)c2ccc3cnc(N)nc3c21
InChIKey: OXBHOAOVRFUPJX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 317.35, ALogP 2.47, HBA 5, HBD 2, PSA 99.82, QED 0.59
Compound (SMILES): CCc1cccc(CC)c1NC(=O)c1c2c(n(C)c1C)-c1nc(Nc3ccc(N4CCC(N5CCCC5)CC4)cc3OC)ncc1CC2
InChIKey: SWZFCGQEKUXWPZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 647.87, ALogP 7.08, HBA 8, HBD 2, PSA 87.55, QED 0.2
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc2c(n1)-c1c(c(C(N)=O)c(C)n1C)CC2
InChIKey: RJGLNSNPZNKTGL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 461.57, ALogP 2.49, HBA 8, HBD 2, PSA 101.54, QED 0.6
Compound (SMILES): CSc1ncc2c(n1)-c1c(c(C(N)=O)cn1C(C)C)CC2
InChIKey: JCICCACMYITOCI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 302.4, ALogP 2.45, HBA 5, HBD 1, PSA 73.8, QED 0.7
Compound (SMILES): CSc1ncc2c(n1)-c1c(c(C(N)=O)cn1CCO)CC2
InChIKey: IJFXPCHHRYCYMT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 304.38, ALogP 0.86, HBA 6, HBD 2, PSA 94.03, QED 0.65
Compound (SMILES): CSc1ncc2ccc3c(C(N)=O)c(C)n(CCO)c3c2n1
InChIKey: LVYDNZIZBIQXIS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 408 nM (pChEMBL 6.389999866485596)
Descriptors: MW 316.39, ALogP 1.71, HBA 6, HBD 2, PSA 94.03, QED 0.56
Compound (SMILES): CSc1ncc2ccc3c(C(N)=O)c(C)n(C(C)C)c3c2n1
InChIKey: PSFMCOGQKUBLKM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 314.41, ALogP 3.29, HBA 5, HBD 1, PSA 73.8, QED 0.59
Compound (SMILES): CSc1ncc2c(n1)-c1c(c(C(N)=O)cn1C1CCNCC1)CC2
InChIKey: QZODUKPIHBQCBB-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Trans-Phosphorylation Assay: Specific peptide or protein substrates are trans-phosphorylated by their specific ser-thr or tyr kinase in the presence of ATP traced with 33P-gamma-ATP, and in the presence of their own optimal buffer and cofactors.At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP is captured by an excess of the ion exchange dowex resin; the resin then settles down to the bottom of the reaction plate by gravity. Supernatant is subsequently withdrawn and transferred into a counting plate, then evaluated by beta -counting.Reagents/Assay Conditionsi. Dowex Resin Preparation500 g of wet resin (SIGMA, custom prepared resin DOWEX 18 200-400 mesh, 2.5 Kg) are weighed out and diluted to 2L in 150 mM sodium formate, pH 3.00.The resin is allowed to settle down (some hours) and then the supernatant is discarded.After three washes as above over a couple of days, the resin is allowed to settle and two volumes (wrt the resin volume) of 150 mM sodium formate buffer are added.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 343.46, ALogP 1.79, HBA 6, HBD 2, PSA 85.83, QED 0.66
Compound (SMILES): CSc1ncc2c(n1)-c1c(c(C(N)=O)cn1[C@H]1CC[C@@H](N)CC1)CC2
InChIKey: BRAYMNJVFKIQLD-TXEJJXNPSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 357.48, ALogP 2.31, HBA 6, HBD 2, PSA 99.82, QED 0.65
Compound (SMILES): CSc1ncc2ccc3c(C(N)=O)cn([C@H]4CC[C@@H](N)CC4)c3c2n1
InChIKey: FRANNCVVJFQWOT-TXEJJXNPSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 355.47, ALogP 2.85, HBA 6, HBD 2, PSA 99.82, QED 0.56
Compound (SMILES): CSc1ncc2ccc3c(C(N)=O)cn(C4CCNCC4)c3c2n1
InChIKey: ZWVHBACWMIHSNL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 341.44, ALogP 2.33, HBA 6, HBD 2, PSA 85.83, QED 0.56
Compound (SMILES): CSc1ncc2ccc3c(C(N)=O)c[nH]c3c2n1
InChIKey: XHEYSFJJPSXTHP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 258.31, ALogP 1.93, HBA 4, HBD 2, PSA 84.66, QED 0.54
Compound (SMILES): CSc1ncc2ccc3c(C(N)=O)cn(CC(C)(C)CN)c3c2n1
InChIKey: SGQNOLAVVZNJKI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 343.46, ALogP 2.39, HBA 6, HBD 2, PSA 99.82, QED 0.55
Compound (SMILES): CCc1cccc(CC)c1NC(=O)c1cn(C)c2c1CCCc1cnc(Nc3ccc(N4CCN(C)CC4)cc3OC)nc1-2
InChIKey: CNSGSATYYDDERW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 593.78, ALogP 5.85, HBA 8, HBD 2, PSA 87.55, QED 0.26
Compound (SMILES): Cc1ccc(-c2cn3ccc(-c4nc5c(C)ncc(C)n5n4)cc3n2)c(C)c1
InChIKey: VVPPGWHZZRJHHT-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition Assay: The PDE10 inhibition assay in 384-well plates was conducted to identify substances for the inhibition of cyclic nucleotide hydrolysis by the PDE10 enzyme. The cyclic nucleotide substrate concentration used was at a Km concentration (25 nM final). PDE10 activity was measured using Scintillation Proximity Assay (SPA)-based methods. PDE10 catalyses the hydrolysis of the intracellular messenger adenosine 5'-cyclic phosphate (cAMP) to the non-cyclic adenosine 5'-monophosphate (AMP). The SPA assay was based upon the selective interaction of the tritiated product with yttrium oxide LEADseeker beads.The assay was performed in 10 uL samples containing 5 uL of 0.3 ng/mL PDE10 final and 5 uL of 3H-5' cAMP (PerkinElmer, NET111540) run at Km of 25 nM final. The assay buffer contained 25 mM HEPES pH 7.4, 2.5 mM Magnesium Chloride and 0.1% BSA. Compound dose response curves were pre-incubated with 5 L of 2PDE10 enzyme for 10 minutes.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 368.44, ALogP 4.34, HBA 6, HBD 0, PSA 60.38, QED 0.46
Compound (SMILES): Cc1ncc(C)n2nc(-c3cc4nc(-c5ccccc5)cn4cc3N3CCCC3)nc12
InChIKey: HSZGXAXFCXLXRX-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition Assay: The PDE10 inhibition assay in 384-well plates was conducted to identify substances for the inhibition of cyclic nucleotide hydrolysis by the PDE10 enzyme. The cyclic nucleotide substrate concentration used was at a Km concentration (25 nM final). PDE10 activity was measured using Scintillation Proximity Assay (SPA)-based methods. PDE10 catalyses the hydrolysis of the intracellular messenger adenosine 5'-cyclic phosphate (cAMP) to the non-cyclic adenosine 5'-monophosphate (AMP). The SPA assay was based upon the selective interaction of the tritiated product with yttrium oxide LEADseeker beads.The assay was performed in 10 uL samples containing 5 uL of 0.3 ng/mL PDE10 final and 5 uL of 3H-5' cAMP (PerkinElmer, NET111540) run at Km of 25 nM final. The assay buffer contained 25 mM HEPES pH 7.4, 2.5 mM Magnesium Chloride and 0.1% BSA. Compound dose response curves were pre-incubated with 5 L of 2PDE10 enzyme for 10 minutes.
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 409.5, ALogP 4.32, HBA 7, HBD 0, PSA 63.62, QED 0.44
Compound (SMILES): Cc1ncc(C)n2nc(-c3ccn4cc(C5CC5)nc4c3)nc12
InChIKey: KWHUYVCUMJDGOA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition Assay: The PDE10 inhibition assay in 384-well plates was conducted to identify substances for the inhibition of cyclic nucleotide hydrolysis by the PDE10 enzyme. The cyclic nucleotide substrate concentration used was at a Km concentration (25 nM final). PDE10 activity was measured using Scintillation Proximity Assay (SPA)-based methods. PDE10 catalyses the hydrolysis of the intracellular messenger adenosine 5'-cyclic phosphate (cAMP) to the non-cyclic adenosine 5'-monophosphate (AMP). The SPA assay was based upon the selective interaction of the tritiated product with yttrium oxide LEADseeker beads.The assay was performed in 10 uL samples containing 5 uL of 0.3 ng/mL PDE10 final and 5 uL of 3H-5' cAMP (PerkinElmer, NET111540) run at Km of 25 nM final. The assay buffer contained 25 mM HEPES pH 7.4, 2.5 mM Magnesium Chloride and 0.1% BSA. Compound dose response curves were pre-incubated with 5 L of 2PDE10 enzyme for 10 minutes.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 304.36, ALogP 2.93, HBA 6, HBD 0, PSA 60.38, QED 0.57
Compound (SMILES): Cc1ncc(C)n2nc(-c3ccn4cc(-c5cccc(C6CC6)c5)nc4c3)nc12
InChIKey: BYMOWCJQUYXECZ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition Assay: The PDE10 inhibition assay in 384-well plates was conducted to identify substances for the inhibition of cyclic nucleotide hydrolysis by the PDE10 enzyme. The cyclic nucleotide substrate concentration used was at a Km concentration (25 nM final). PDE10 activity was measured using Scintillation Proximity Assay (SPA)-based methods. PDE10 catalyses the hydrolysis of the intracellular messenger adenosine 5'-cyclic phosphate (cAMP) to the non-cyclic adenosine 5'-monophosphate (AMP). The SPA assay was based upon the selective interaction of the tritiated product with yttrium oxide LEADseeker beads.The assay was performed in 10 uL samples containing 5 uL of 0.3 ng/mL PDE10 final and 5 uL of 3H-5' cAMP (PerkinElmer, NET111540) run at Km of 25 nM final. The assay buffer contained 25 mM HEPES pH 7.4, 2.5 mM Magnesium Chloride and 0.1% BSA. Compound dose response curves were pre-incubated with 5 L of 2PDE10 enzyme for 10 minutes.
Measurement: IC50 = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 380.46, ALogP 4.6, HBA 6, HBD 0, PSA 60.38, QED 0.46
Compound (SMILES): Cc1nccn2nc(-c3ccn4c(C)c(-c5ccccc5)nc4c3)nc12
InChIKey: IKTOWFBFVMJQKU-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition Assay: The PDE10 inhibition assay in 384-well plates was conducted to identify substances for the inhibition of cyclic nucleotide hydrolysis by the PDE10 enzyme. The cyclic nucleotide substrate concentration used was at a Km concentration (25 nM final). PDE10 activity was measured using Scintillation Proximity Assay (SPA)-based methods. PDE10 catalyses the hydrolysis of the intracellular messenger adenosine 5'-cyclic phosphate (cAMP) to the non-cyclic adenosine 5'-monophosphate (AMP). The SPA assay was based upon the selective interaction of the tritiated product with yttrium oxide LEADseeker beads.The assay was performed in 10 uL samples containing 5 uL of 0.3 ng/mL PDE10 final and 5 uL of 3H-5' cAMP (PerkinElmer, NET111540) run at Km of 25 nM final. The assay buffer contained 25 mM HEPES pH 7.4, 2.5 mM Magnesium Chloride and 0.1% BSA. Compound dose response curves were pre-incubated with 5 L of 2PDE10 enzyme for 10 minutes.
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 340.39, ALogP 3.72, HBA 6, HBD 0, PSA 60.38, QED 0.49
Compound (SMILES): Cc1c(C(=O)Nc2ccc(Oc3ccnc(NC(=O)C4CC4)c3)cn2)c(=O)n(-c2ccccc2)n1C
InChIKey: UMMZZOSIEGYDTO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: KDR (h) is incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 0.33 mg/mL myelin basic protein, 10 mM MgAcetate and [.gamma.-.sup.33P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 3% phosphoric acid solution. 10 .mu.L, of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: Kd = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 484.52, ALogP 3.67, HBA 8, HBD 2, PSA 120.14, QED 0.41
Compound (SMILES): Cc1c(C(=O)Nc2ccc(Oc3ccnc(C(N)=O)c3)c(F)c2)c(=O)n(-c2ccccc2)n1C
InChIKey: AEUQVUHYNJZUMV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: KDR (h) is incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 0.33 mg/mL myelin basic protein, 10 mM MgAcetate and [.gamma.-.sup.33P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 3% phosphoric acid solution. 10 .mu.L, of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: Kd = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 461.45, ALogP 3.16, HBA 7, HBD 2, PSA 121.24, QED 0.46
Compound (SMILES): Cc1c(C(=O)Nc2ccc(Oc3ccnc(NC(=O)C4CC4)c3)c(F)c2)c(=O)n(-c2ccccc2)n1C
InChIKey: ODYPDMJDOCOPAV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: KDR (h) is incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 0.33 mg/mL myelin basic protein, 10 mM MgAcetate and [.gamma.-.sup.33P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 3% phosphoric acid solution. 10 .mu.L, of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: Kd = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 501.52, ALogP 4.41, HBA 7, HBD 2, PSA 107.25, QED 0.39
Compound (SMILES): Cc1c(C(=O)Nc2ccc(Oc3ccnc(NC(=O)C4CC4)c3)cc2)c(=O)n(-c2ccccc2)n1C
InChIKey: CICHSTJOLCRZKB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: KDR (h) is incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 0.33 mg/mL myelin basic protein, 10 mM MgAcetate and [.gamma.-.sup.33P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 3% phosphoric acid solution. 10 .mu.L, of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: Kd = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 483.53, ALogP 4.27, HBA 7, HBD 2, PSA 107.25, QED 0.41
Compound (SMILES): CCC(CC)CC1(O)CCN(C(=O)Nc2cc(Oc3ccc(F)cc3)cc(Oc3ccc(C4(C(=O)O)CC4)cc3)c2)CC1
InChIKey: UZPSRIVFHKJDOL-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Fluorescence-Based Assay: Chinese hamster ovary (CHO) cells overexpressing the human S1P2 gene were cultured in a Ham's F12 medium containing 10% fetal bovine serum (FBS), an antibiotic/antifungal agent and G418. CHO cells overexpressing the rat S1P2 gene were cultured in a Ham's F12 medium containing 10% FBS, penicillin/streptomycin and blasticidin S. The cultured cells were incubated in a Fura2-AM solution (5 uM) [a Ham's F12 medium containing FBS (10%), HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM)] at 37 C. for 60 minutes. The cells were washed twice with a Hanks' balanced saline containing HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM) and immersed in the same solution. A plate was mounted on a fluorescence-based drug screening system and the intracellular calcium ion concentration was measured for 30 seconds without stimulation.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 590.69, ALogP 7.71, HBA 5, HBD 3, PSA 108.33, QED 0.21
Compound (SMILES): CCNC(=O)c1ccc(Oc2cc(NC(=O)N3CCC(O)(CC(CC)CC)CC3)cc(Oc3ccc(F)cc3)c2)cc1
InChIKey: OHOPIJDKZBJLAT-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P47752
Assay: Fluorescence-Based Assay: Chinese hamster ovary (CHO) cells overexpressing the human S1P2 gene were cultured in a Ham's F12 medium containing 10% fetal bovine serum (FBS), an antibiotic/antifungal agent and G418. CHO cells overexpressing the rat S1P2 gene were cultured in a Ham's F12 medium containing 10% FBS, penicillin/streptomycin and blasticidin S. The cultured cells were incubated in a Fura2-AM solution (5 uM) [a Ham's F12 medium containing FBS (10%), HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM)] at 37 C. for 60 minutes. The cells were washed twice with a Hanks' balanced saline containing HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM) and immersed in the same solution. A plate was mounted on a fluorescence-based drug screening system and the intracellular calcium ion concentration was measured for 30 seconds without stimulation.
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 577.7, ALogP 7.35, HBA 5, HBD 3, PSA 100.13, QED 0.22
Compound (SMILES): CCC(CC)CC1(O)CCN(C(=O)Nc2cc(Oc3ccc(F)cc3)cc(Oc3ccc(C(=O)N4CCCC(O)C4)cc3)c2)CC1
InChIKey: BZVBOQNGUPRKHW-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P47752
Assay: Fluorescence-Based Assay: Chinese hamster ovary (CHO) cells overexpressing the human S1P2 gene were cultured in a Ham's F12 medium containing 10% fetal bovine serum (FBS), an antibiotic/antifungal agent and G418. CHO cells overexpressing the rat S1P2 gene were cultured in a Ham's F12 medium containing 10% FBS, penicillin/streptomycin and blasticidin S. The cultured cells were incubated in a Fura2-AM solution (5 uM) [a Ham's F12 medium containing FBS (10%), HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM)] at 37 C. for 60 minutes. The cells were washed twice with a Hanks' balanced saline containing HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM) and immersed in the same solution. A plate was mounted on a fluorescence-based drug screening system and the intracellular calcium ion concentration was measured for 30 seconds without stimulation.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 633.76, ALogP 7.19, HBA 6, HBD 3, PSA 111.57, QED 0.22
Compound (SMILES): CC(C)CC1(O)CN(C(=O)Nc2cc(Oc3ccc(F)cc3)cc(Oc3ccc(C(C)(C)C(=O)O)cc3)c2)C1
InChIKey: HKSAGIGRQWXHMH-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Fluorescence-Based Assay: Chinese hamster ovary (CHO) cells overexpressing the human S1P2 gene were cultured in a Ham's F12 medium containing 10% fetal bovine serum (FBS), an antibiotic/antifungal agent and G418. CHO cells overexpressing the rat S1P2 gene were cultured in a Ham's F12 medium containing 10% FBS, penicillin/streptomycin and blasticidin S. The cultured cells were incubated in a Fura2-AM solution (5 uM) [a Ham's F12 medium containing FBS (10%), HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM)] at 37 C. for 60 minutes. The cells were washed twice with a Hanks' balanced saline containing HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM) and immersed in the same solution. A plate was mounted on a fluorescence-based drug screening system and the intracellular calcium ion concentration was measured for 30 seconds without stimulation.
Measurement: IC50 = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 536.6, ALogP 6.4, HBA 5, HBD 3, PSA 108.33, QED 0.29
Compound (SMILES): CC(C)CC1(O)CCN(C(=O)Nc2cc(Oc3ccc(F)cc3)cc(C(=O)Oc3ccc(C(C)(C)C(=O)O)cc3)c2)CC1
InChIKey: HCNPUNDFLQNIOB-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Fluorescence-Based Assay: Chinese hamster ovary (CHO) cells overexpressing the human S1P2 gene were cultured in a Ham's F12 medium containing 10% fetal bovine serum (FBS), an antibiotic/antifungal agent and G418. CHO cells overexpressing the rat S1P2 gene were cultured in a Ham's F12 medium containing 10% FBS, penicillin/streptomycin and blasticidin S. The cultured cells were incubated in a Fura2-AM solution (5 uM) [a Ham's F12 medium containing FBS (10%), HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM)] at 37 C. for 60 minutes. The cells were washed twice with a Hanks' balanced saline containing HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM) and immersed in the same solution. A plate was mounted on a fluorescence-based drug screening system and the intracellular calcium ion concentration was measured for 30 seconds without stimulation.
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 592.66, ALogP 6.6, HBA 6, HBD 3, PSA 125.4, QED 0.19
Compound (SMILES): CC(C)CC1(O)CCN(C(=O)Nc2cc(Oc3ccc(F)cc3)cc(Oc3ccc(C(C)(C)C(=O)O)cc3)c2)CC1
InChIKey: MBTKFRQXHPGCLC-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Fluorescence-Based Assay: Chinese hamster ovary (CHO) cells overexpressing the human S1P2 gene were cultured in a Ham's F12 medium containing 10% fetal bovine serum (FBS), an antibiotic/antifungal agent and G418. CHO cells overexpressing the rat S1P2 gene were cultured in a Ham's F12 medium containing 10% FBS, penicillin/streptomycin and blasticidin S. The cultured cells were incubated in a Fura2-AM solution (5 uM) [a Ham's F12 medium containing FBS (10%), HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM)] at 37 C. for 60 minutes. The cells were washed twice with a Hanks' balanced saline containing HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM) and immersed in the same solution. A plate was mounted on a fluorescence-based drug screening system and the intracellular calcium ion concentration was measured for 30 seconds without stimulation.
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 564.65, ALogP 7.18, HBA 5, HBD 3, PSA 108.33, QED 0.25
Compound (SMILES): CCC(CC)CC1(O)CCN(C(=O)Nc2cccc(Oc3cc(F)cc(C(F)(F)F)c3)c2)CC1
InChIKey: JYUZIAXLZMPCJX-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P47752
Assay: Fluorescence-Based Assay: Chinese hamster ovary (CHO) cells overexpressing the human S1P2 gene were cultured in a Ham's F12 medium containing 10% fetal bovine serum (FBS), an antibiotic/antifungal agent and G418. CHO cells overexpressing the rat S1P2 gene were cultured in a Ham's F12 medium containing 10% FBS, penicillin/streptomycin and blasticidin S. The cultured cells were incubated in a Fura2-AM solution (5 uM) [a Ham's F12 medium containing FBS (10%), HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM)] at 37 C. for 60 minutes. The cells were washed twice with a Hanks' balanced saline containing HEPES buffer (20 mM, pH 7.2 to 7.5) and probenecid (2.5 mM) and immersed in the same solution. A plate was mounted on a fluorescence-based drug screening system and the intracellular calcium ion concentration was measured for 30 seconds without stimulation.
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 482.52, ALogP 6.82, HBA 3, HBD 2, PSA 61.8, QED 0.43
Compound (SMILES): NC1=NC2(CO1)c1cc(Br)ccc1OCC21CCCO1
InChIKey: XPMGWHVEGYGUIQ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 73300 nM (pChEMBL 4.130000114440918)
Descriptors: MW 339.19, ALogP 1.93, HBA 5, HBD 1, PSA 66.07, QED 0.78
Compound (SMILES): NC1=NC2(CO1)c1cc(Br)ccc1OCC21COC1
InChIKey: LUQRVIKCMJFRLZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 59600 nM (pChEMBL 4.21999979019165)
Descriptors: MW 325.16, ALogP 1.4, HBA 5, HBD 1, PSA 66.07, QED 0.78
Compound (SMILES): NC1=NC2(CO1)c1cc(Br)ccc1OC1(CCC1)C21COC1
InChIKey: RUGHZTZOMNIPQG-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 33800 nM (pChEMBL 4.46999979019165)
Descriptors: MW 365.23, ALogP 2.32, HBA 5, HBD 1, PSA 66.07, QED 0.77
Compound (SMILES): COCc1cnn(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: NRTIHHVWKLDASP-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 12600 nM (pChEMBL 4.900000095367432)
Descriptors: MW 396.45, ALogP 1.89, HBA 8, HBD 1, PSA 93.12, QED 0.85
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC1(CCC1)C21COC1
InChIKey: APMDRJOSPMXZBV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 1560 nM (pChEMBL 5.809999942779541)
Descriptors: MW 364.4, ALogP 2.02, HBA 7, HBD 1, PSA 91.85, QED 0.83
Compound (SMILES): CC1(C)Oc2ccc(Br)cc2C2(COC(N)=N2)C12COC2
InChIKey: BFCFOLFRUMYREH-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 11700 nM (pChEMBL 4.929999828338623)
Descriptors: MW 353.22, ALogP 2.18, HBA 5, HBD 1, PSA 66.07, QED 0.78
Compound (SMILES): C[C@H]1Oc2ccc(Br)cc2[C@@]2(COC(N)=N2)C12COC2
InChIKey: UGDRTDNGDMXMII-CLAHSXSESA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Test Example 1: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence. The amino acid sequence of the "core" peptide of the substrate is SEVNLDAEFK (SEQ ID NO:2). The amino terminus was derivatized with (7-methoxycoumarin-4-yl)acetyl (MCA), and the epsilon amine of the lysine side chain of the terminal residue (K in sequence SEVNLDAEFK (SEQ ID NO:2)) was derivatized with 2,4-dinitrophenyl (DNP). Assays were performed in a buffer of 0.1 M sodium acetate, pH 4.4, 0.08% 3-[(3-Cholamidopropyl)dimethylammonio]propanesulfonate (CHAPS), 0.005% Tween80. BACE1 enzyme (final concentration 65 nM) was pre-incubated with test compounds for 15 minutes at room temperature. Fluorescence intensities were measured 60 minutes after addition of the substrate (final concentration 3 uM) by Tecan Safire2.
Measurement: IC50 = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 339.19, ALogP 1.79, HBA 5, HBD 1, PSA 66.07, QED 0.78
Compound (SMILES): C[C@@H]1Oc2ccc(Br)cc2[C@@]2(COC(N)=N2)C12COC2
InChIKey: UGDRTDNGDMXMII-RTHLEPHNSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 39700 nM (pChEMBL 4.400000095367432)
Descriptors: MW 339.19, ALogP 1.79, HBA 5, HBD 1, PSA 66.07, QED 0.78
Compound (SMILES): NC1=NC2(CO1)c1cc(Br)ccc1OCC21CCC1
InChIKey: GOBYJQFUBCMBOX-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 61300 nM (pChEMBL 4.210000038146973)
Descriptors: MW 323.19, ALogP 2.55, HBA 4, HBD 1, PSA 56.84, QED 0.8