[Protein kinase inhibitors--screening of new molecular target therapeutics].
Protein kinases are critical enzymes in regulating cellular growth and differentiation. Protein tyrosine kinases are potential targets for new anti-cancer therapeutics because they are encoded by many oncogenes. We first identified herbimycin A as an inhibitor of Src tyrosine kinase by screening agents that cause morphological reversion of v-src oncogene transformed cells. We next developed a method for evaluating inhibitors of oncogenic signal transduction pathways based on different growth abilities between normal and transformed cells in a defined serum free medium and isolated new tyrosine kinase inhibitors angelmicins. Recently, we developed 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 on a single gel. This system should be useful for evaluating specificities and screening of protein kinase inhibitors.
Uehara
Y
Y
Dept. of Bioactive Molecules, National Institute of Health.
D016475:3T3 Cells / Q000166:cytology; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology; D016227:Benzoquinones; D002455:Cell Division; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047029:Lactams, Macrocyclic; D051379:Mice; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000880:Anthraquinones; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D011809:Quinones; C083655:angelmicin B; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases