Evaluation of protein kinase inhibitors in an assay system containing multiple protein kinase activities.
Specificities of several known protein kinase inhibitors were evaluated using an assay system in which activities of protein kinase A, protein kinase C, protein tyrosine kinase and calmodulin-dependent protein kinase III were simultaneously detected. Inhibitory spectra of H-89, K252a, H-7, staurosporine, tyrphostin and herbimycin A observed in the assay system were similar to those reported in the purified protein kinase assay systems. It was also found that KN-62 selectively inhibited calmodulin-dependent protein kinase III activity. These data suggest that the assay system may be effective and practicable in evaluating specificities and screening of new protein kinase inhibitors.
Li
P M
PM
Department of Bioactive Molecules, National Institute of Health, Tokyo, Japan.
Fukazawa
H
H
Mizuno
S
S
Uehara
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives; D016475:3T3 Cells; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004533:Egtazic Acid / Q000494:pharmacology; D016391:Genes, src; D026121:Indole Alkaloids; D007546:Isoquinolines / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020032:Tyrphostins
D000470:Alkaloids; D016227:Benzoquinones; D002227:Carbazoles; D002396:Catechols; D026121:Indole Alkaloids; D007546:Isoquinolines; D047029:Lactams, Macrocyclic; D009570:Nitriles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011809:Quinones; D013449:Sulfonamides; D020032:Tyrphostins; C060152:tyrphostin 47; D017828:Rifabutin; D004533:Egtazic Acid; C063302:KN 62; C020754:herbimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049985:staurosporine aglycone; D000242:Cyclic AMP; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate