lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)[C@@H]1CC[C@@H](C)CC1OC(=O)NC1CCCCC1
InChIKey: PDDIETGPTXAEPC-YISXUXMPSA-N
Target: Epoxide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07099
Assay: Activity Assay: The invention also provide methods for assaying for epoxide hydrolase activity as diagnostic assay to identify individuals at increased risk for hypertension and/or those that would benefit from the therapeutic methods of the invention. Any of a number of standard assays for determining epoxide hydrolase activity can be used. For example, suitable assays are described in Gill, et al., Anal Biochem 131, 273-282 (1983); and Borhan, et al., Analytical Biochemistry 231, 188-200 (1995)). Suitable in vitro assays are described in Zeldin et al. J Biol. Chem. 268:6402-6407 (1993). Suitable in vivo assays are described in Zeldin et al. Arch Biochem Biophys 330:87-96 (1996). Assays for epoxide hydrolase using both putative natural substrates and surrogate substrates have been reviewed (see, Hammock, et al. In: Methods in Enzymology, Volume III, Steroids and Isoprenoids, Part B, (Law, J. H. and H. C. Rilling, eds. 1985), Academic Press, Orlando, Fla., pp. 303-311).
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 281.44, ALogP 4.51, HBA 2, HBD 1, PSA 38.33, QED 0.83
Compound (SMILES): O=C(NC1CCCCC1)OCCCCC1CCCCC1
InChIKey: MLWZPBFHICOPQN-UHFFFAOYSA-N
Target: Epoxide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07099
Assay: Activity Assay: The invention also provide methods for assaying for epoxide hydrolase activity as diagnostic assay to identify individuals at increased risk for hypertension and/or those that would benefit from the therapeutic methods of the invention. Any of a number of standard assays for determining epoxide hydrolase activity can be used. For example, suitable assays are described in Gill, et al., Anal Biochem 131, 273-282 (1983); and Borhan, et al., Analytical Biochemistry 231, 188-200 (1995)). Suitable in vitro assays are described in Zeldin et al. J Biol. Chem. 268:6402-6407 (1993). Suitable in vivo assays are described in Zeldin et al. Arch Biochem Biophys 330:87-96 (1996). Assays for epoxide hydrolase using both putative natural substrates and surrogate substrates have been reviewed (see, Hammock, et al. In: Methods in Enzymology, Volume III, Steroids and Isoprenoids, Part B, (Law, J. H. and H. C. Rilling, eds. 1985), Academic Press, Orlando, Fla., pp. 303-311).
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 281.44, ALogP 4.8, HBA 2, HBD 1, PSA 38.33, QED 0.71
Compound (SMILES): C=C(C)CCOC(=O)NC1CCCCC1
InChIKey: UKDWQYZBYACSCJ-UHFFFAOYSA-N
Target: Epoxide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07099
Assay: Activity Assay: The invention also provide methods for assaying for epoxide hydrolase activity as diagnostic assay to identify individuals at increased risk for hypertension and/or those that would benefit from the therapeutic methods of the invention. Any of a number of standard assays for determining epoxide hydrolase activity can be used. For example, suitable assays are described in Gill, et al., Anal Biochem 131, 273-282 (1983); and Borhan, et al., Analytical Biochemistry 231, 188-200 (1995)). Suitable in vitro assays are described in Zeldin et al. J Biol. Chem. 268:6402-6407 (1993). Suitable in vivo assays are described in Zeldin et al. Arch Biochem Biophys 330:87-96 (1996). Assays for epoxide hydrolase using both putative natural substrates and surrogate substrates have been reviewed (see, Hammock, et al. In: Methods in Enzymology, Volume III, Steroids and Isoprenoids, Part B, (Law, J. H. and H. C. Rilling, eds. 1985), Academic Press, Orlando, Fla., pp. 303-311).
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 211.3, ALogP 3.01, HBA 2, HBD 1, PSA 38.33, QED 0.73
Compound (SMILES): O=C(NC1CCCCC1)OCCCCc1ccc([N+](=O)[O-])cc1
InChIKey: UTNINXYKTXZOBE-UHFFFAOYSA-N
Target: Epoxide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07099
Assay: Activity Assay: The invention also provide methods for assaying for epoxide hydrolase activity as diagnostic assay to identify individuals at increased risk for hypertension and/or those that would benefit from the therapeutic methods of the invention. Any of a number of standard assays for determining epoxide hydrolase activity can be used. For example, suitable assays are described in Gill, et al., Anal Biochem 131, 273-282 (1983); and Borhan, et al., Analytical Biochemistry 231, 188-200 (1995)). Suitable in vitro assays are described in Zeldin et al. J Biol. Chem. 268:6402-6407 (1993). Suitable in vivo assays are described in Zeldin et al. Arch Biochem Biophys 330:87-96 (1996). Assays for epoxide hydrolase using both putative natural substrates and surrogate substrates have been reviewed (see, Hammock, et al. In: Methods in Enzymology, Volume III, Steroids and Isoprenoids, Part B, (Law, J. H. and H. C. Rilling, eds. 1985), Academic Press, Orlando, Fla., pp. 303-311).
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 320.39, ALogP 3.98, HBA 4, HBD 1, PSA 81.47, QED 0.47
Compound (SMILES): COc1ccc(Cl)cc1CC1CN/C(=N\Oc2ccc(F)cc2)CN(C(=O)N[C@H](C)c2ccc(CC(=O)O)cc2)C1=O
InChIKey: ITTFWXDRJJVNPO-ZZWBGTBQSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 597.04, ALogP 4.57, HBA 6, HBD 3, PSA 129.56, QED 0.31
Compound (SMILES): COc1ccc(Cl)cc1CC1CN/C(=N\Oc2cc(F)cc(F)c2)CN(C(=O)N[C@H](C)c2ccc(CC(=O)O)cc2)C1=O
InChIKey: UMCXBBMZQWEAHW-OQHSHRKDSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 615.03, ALogP 4.71, HBA 6, HBD 3, PSA 129.56, QED 0.3
Compound (SMILES): COc1ccc(Cl)cc1CC1CN/C(=N\Oc2ccccn2)CN(C(=O)N[C@H](C)c2ccc(CC(=O)O)cc2)C1=O
InChIKey: IQVXOIZPBCFWIH-ZZWBGTBQSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 580.04, ALogP 3.82, HBA 7, HBD 3, PSA 142.45, QED 0.32
Compound (SMILES): CC[C@@H](NC(=O)N1C/C(=N/Oc2cc(F)cc(F)c2)NCC(Cc2cc(Cl)ccc2OC)C1=O)c1ccc(C(=O)O)c(O)c1
InChIKey: XOLVVPJVGKWJAQ-VCUSLETLSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 631.03, ALogP 4.87, HBA 7, HBD 4, PSA 149.79, QED 0.24
Compound (SMILES): CC[C@@H](NC(=O)N1C/C(=N/Oc2ccccc2)NCC(Cc2cc(Cl)ccc2OC)C1=O)c1cncc(C(=O)O)c1
InChIKey: MKXHMSSNRUXAEY-PIFIWZBESA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 580.04, ALogP 4.29, HBA 7, HBD 3, PSA 142.45, QED 0.32
Compound (SMILES): COc1ccc(Cl)cc1CC1CN/C(=N\Oc2cc(F)cc(F)c2)CN(C(=O)NCc2ccc(C(=O)O)c(N)c2)C1=O
InChIKey: HKBSZXIBATXCQO-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 601.99, ALogP 3.8, HBA 7, HBD 4, PSA 155.58, QED 0.22
Compound (SMILES): CC[C@@H](NC(=O)N1C/C(=N/Oc2ccccc2)NCC(Cc2cc(Cl)ccc2OC)C1=O)C(=O)Nc1nnn[nH]1
InChIKey: WVUPKAULRXZDRV-LRTDYKAYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 570.01, ALogP 1.97, HBA 9, HBD 4, PSA 175.82, QED 0.28
Compound (SMILES): CC[C@@H](NC(=O)N1C/C(=N/Oc2ccccc2)NCC(Cc2cc(Cl)ccc2OC)C1=O)c1ccc(CC(=O)O)cc1
InChIKey: DZBVADVKQFGEER-ANWICMFUSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 593.08, ALogP 4.82, HBA 6, HBD 3, PSA 129.56, QED 0.29
Compound (SMILES): CC[C@@H](NC(=O)N1C/C(=N/Oc2ccccc2)NCC(Cc2cc(Cl)ccc2OC)C1=O)c1nc(C(=O)O)cs1
InChIKey: UBQNTABUSXITSX-UUSAFJCLSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 586.07, ALogP 4.35, HBA 8, HBD 3, PSA 142.45, QED 0.31
Compound (SMILES): CC[C@@H](NC(=O)N1C/C(=N/Oc2ccccc2)NCC(Cc2cc(Cl)ccc2OC)C1=O)c1cccc(C(=O)O)c1
InChIKey: WHRJFSQXYYUJCK-NRWPOFLRSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 579.05, ALogP 4.89, HBA 6, HBD 3, PSA 129.56, QED 0.31
Compound (SMILES): CC[C@@H](NC(=O)N1C/C(=N/Oc2ccccc2)NCC(Cc2cc(Cl)ccc2OC)C1=O)c1ccc(C(=O)O)c(N)c1
InChIKey: LHASZEBEQGPCFM-GBAXHLBXSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 594.07, ALogP 4.47, HBA 7, HBD 4, PSA 155.58, QED 0.21
Compound (SMILES): CC[C@@H](NC(=O)N1Cc2nnc(O)n2CC(Cc2cc(Cl)ccc2OC)C1=O)c1ccc(C(=O)O)c(N)c1
InChIKey: VBVDJCSKERVLGI-XCWJXAQQSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 542.98, ALogP 2.99, HBA 9, HBD 4, PSA 172.9, QED 0.33
Compound (SMILES): CCC[C@@H](NC(=O)N1CC2=NOCC(=O)N2CC(Cc2cc(Cl)ccc2OC)C1=O)c1ccc(C(=O)O)c(N)c1
InChIKey: XGZXMBNUKNJTHA-FBLFFUNLSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 572.02, ALogP 3.05, HBA 8, HBD 3, PSA 163.86, QED 0.41
Compound (SMILES): CCC[C@@H](NC(=O)N1C/C(=N/OCC)NCC(Cc2cc(F)ccc2OC)C1=O)c1ccc(C(=O)O)c(N)c1
InChIKey: MDBSJWOREXSLIW-LMNIDFBRSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 543.6, ALogP 3.31, HBA 7, HBD 4, PSA 155.58, QED 0.26
Compound (SMILES): CCC[C@@H](NC(=O)N1C/C(=N/OCC)NCC(Cc2cc(Cl)ccc2F)C1=O)c1ccc(C(=O)O)c(N)c1
InChIKey: FSPYZEQTABRBRD-IVAFLUGOSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibitory Assay: The inhibitory activity of the compounds of the present invention for recombinant human chymase was measured by the method of Pasztor et al. (Pasztor et al., Acta. Biol. Hung. 42: 285-95, 1991). That is, recombinant human chymase was diluted to an appropriate concentration by a 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution, and 0.01% (v/v) Triton X-100 to obtain an enzyme solution. A 10 mM dimethyl sulfoxide (hereinafter referred to as DMSO) solution of Suc-Ala-Ala-Pro-Phe-MCA (Peptide Institute) was diluted 20-fold at the time of use by 50 mM tris-hydrochloride buffer (pH 7.5), 1M sodium chloride solution and 0.01% (v/v) Triton X-100 to obtain the substrate solution. 75 ul of the enzyme solution was mixed with 5 ul of the test compound in a DMSO solution, and incubated for 10 minutes. Then 20 ul of the substrate solution was added to the mixture and reacted for a further 10 minutes at room temperature.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 548.02, ALogP 3.95, HBA 6, HBD 4, PSA 146.35, QED 0.27
Compound (SMILES): Cc1cccc(Oc2ccc(-c3cc(C4CCCC4)nc(N)c3C(=N)N)cc2)c1
InChIKey: VIOHUZGVFNUSPB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 386.5, ALogP 5.37, HBA 4, HBD 3, PSA 98.01, QED 0.41
Compound (SMILES): CC(C)(C)OC(=O)NC1CCN(c2cc(-c3ccc(Oc4ccccc4)cc3)c3c(N)n[nH]c3n2)C1
InChIKey: MOANIRQCGDGDRF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 8640 nM (pChEMBL 5.059999942779541)
Descriptors: MW 486.58, ALogP 5.1, HBA 7, HBD 3, PSA 118.39, QED 0.36
Compound (SMILES): COc1ccc(Oc2cc(-c3ccc(Oc4ccccc4)cc3)c3c(N)n[nH]c3n2)cc1
InChIKey: PPEKDYIEZYPINB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 27910 nM (pChEMBL 4.550000190734863)
Descriptors: MW 424.46, ALogP 5.8, HBA 6, HBD 2, PSA 95.28, QED 0.36
Compound (SMILES): Cc1csc(NC(=O)NC2CCN(c3cc(-c4ccc(Oc5ccccc5)cc4)c4c(N)n[nH]c4n3)C2)n1
InChIKey: NVKLMARNYJAHNQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 9410 nM (pChEMBL 5.03000020980835)
Descriptors: MW 526.63, ALogP 5.16, HBA 8, HBD 4, PSA 134.08, QED 0.24
Compound (SMILES): CC(C)Oc1ccc(-c2cncc3[nH]nc(N)c23)cc1
InChIKey: CMGXWQAMCONAEJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 9310 nM (pChEMBL 5.03000020980835)
Descriptors: MW 268.32, ALogP 2.99, HBA 4, HBD 2, PSA 76.82, QED 0.77
Compound (SMILES): Nc1n[nH]c2cncc(-c3ccc(OC4CCCC4)cc3)c12
InChIKey: NRLRZCBVHOOXQK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 9490 nM (pChEMBL 5.019999980926514)
Descriptors: MW 294.36, ALogP 3.53, HBA 4, HBD 2, PSA 76.82, QED 0.77
Compound (SMILES): Nc1n[nH]c2cncc(-c3ccc(C(=O)N4CCCC4)cc3)c12
InChIKey: XEHOJESEYRTUMJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 40570 nM (pChEMBL 4.389999866485596)
Descriptors: MW 307.36, ALogP 2.44, HBA 4, HBD 2, PSA 87.9, QED 0.76
Compound (SMILES): Nc1n[nH]c2c(-c3ccc(NC(=O)c4ccccc4)cc3)ncc(-c3ccc(Oc4ccccc4)cc3)c12
InChIKey: WZBBWWSMAYMNCE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 14860 nM (pChEMBL 4.829999923706055)
Descriptors: MW 497.56, ALogP 6.92, HBA 5, HBD 3, PSA 105.92, QED 0.23
Compound (SMILES): CS(=O)(=O)Nc1cccc(-c2ncc(-c3ccc(Oc4ccccc4)cc3)c3c(N)n[nH]c23)c1
InChIKey: JKKZHCSFKYWXIC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 471.54, ALogP 5.04, HBA 6, HBD 3, PSA 122.99, QED 0.32
Compound (SMILES): Nc1n[nH]c2c(-c3ccc(Cl)c(Cl)c3)ncc(-c3ccc(Oc4ccccc4)cc3)c12
InChIKey: PWRAELROOGUUHE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 9180 nM (pChEMBL 5.039999961853027)
Descriptors: MW 447.33, ALogP 6.97, HBA 4, HBD 2, PSA 76.82, QED 0.31
Compound (SMILES): Nc1n[nH]c2c(-c3ccc(O)cc3)ncc(-c3ccc(Oc4ccccc4)cc3)c12
InChIKey: NHEFGBDPAKZURZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 394.43, ALogP 5.37, HBA 5, HBD 3, PSA 97.05, QED 0.38
Compound (SMILES): Nc1n[nH]c2c(-c3ccc4[nH]ccc4c3)ncc(-c3ccc(Oc4ccccc4)cc3)c12
InChIKey: LNRIEAVCDXMKOO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 417.47, ALogP 6.15, HBA 4, HBD 3, PSA 92.61, QED 0.32
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2ncc(-c3ccc(Oc4ccccc4)cc3)c3c(N)n[nH]c23)cc1
InChIKey: RMNHYPZVNFTHCB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 471.54, ALogP 5.04, HBA 6, HBD 3, PSA 122.99, QED 0.32
Compound (SMILES): CC(C)COc1cccc(-c2ncc(-c3ccc(Oc4ccccc4)cc3)c3c(N)n[nH]c23)c1
InChIKey: PYAKIBMUNIZLRH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 450.54, ALogP 6.7, HBA 5, HBD 2, PSA 86.05, QED 0.29
Compound (SMILES): Cc1ccccc1-c1ncc(-c2ccc(Oc3ccccc3)cc2)c2c(N)n[nH]c12
InChIKey: XFVFGDHPBBKJKB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 12680 nM (pChEMBL 4.900000095367432)
Descriptors: MW 392.46, ALogP 5.97, HBA 4, HBD 2, PSA 76.82, QED 0.39
Compound (SMILES): Nc1n[nH]c2c(-c3cccc(C(F)(F)F)c3)ncc(-c3ccc(Oc4ccccc4)cc3)c12
InChIKey: CZFRUYPEOMPCLL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 16090 nM (pChEMBL 4.789999961853027)
Descriptors: MW 446.43, ALogP 6.69, HBA 4, HBD 2, PSA 76.82, QED 0.32
Compound (SMILES): Nc1n[nH]c2c(-c3cccc(OC(F)(F)F)c3)ncc(-c3ccc(Oc4ccccc4)cc3)c12
InChIKey: UEJWSRRXTLCNRD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 13840 nM (pChEMBL 4.860000133514404)
Descriptors: MW 462.43, ALogP 6.57, HBA 5, HBD 2, PSA 86.05, QED 0.31
Compound (SMILES): Nc1n[nH]c2nc(-c3cccs3)nc(-c3ccc(Oc4ccccc4)cc3)c12
InChIKey: CZOHLBYBHIKMRV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 385.45, ALogP 5.12, HBA 6, HBD 2, PSA 89.71, QED 0.45
Compound (SMILES): COc1cccc(-c2cnc(Nc3ccccc3)c3[nH]nc(N)c23)c1
InChIKey: QKNXFQUKBFUGCN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 uM), ATP (20 uM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT in 1.6% DMSO), with a final volume of 30 uL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 ul of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 331.38, ALogP 3.96, HBA 5, HBD 3, PSA 88.85, QED 0.53