Potent selective inhibition of 7-O-methyl UCN-01 against protein kinase C

Autor:	I, Takahashi, E, Kobayashi, H, Nakano, C, Murakata, H, Saitoh, K, Suzuki, T, Tamaoki
Rok vydání:	1990
Předmět:	Cell Survival Antineoplastic Agents Staurosporine Enzyme Activation Kinetics Mice Alkaloids Tumor Cells Cultured Animals Tetradecanoylphorbol Acetate Leukemia Erythroblastic Acute Protein Kinase Inhibitors Cells Cultured Protein Kinase C
Zdroj:	The Journal of pharmacology and experimental therapeutics. 255(3)
ISSN:	0022-3565
Popis:	UCN-01 is a staurosporine-related compound that was isolated from the culture broth of Streptomyces sp. and shows potent and selective inhibitory activity against protein kinase C. Cellular inhibitory activity of UCN-01 against protein kinase C and cytotoxicity of UCN-01 were compared with those of staurosporine. When the mechanism of inhibitory activity was investigated in vitro, UCN-01 as well as staurosporine inhibited the activity of the catalytic domain of protein kinase C. In spite of direct inhibition against the catalytic domain of protein kinase C, cytotoxicity of UCN-01 was much lower than that of staurosporine. In addition, UCN-01 showed more selective inhibitory activity against protein kinase C than did staurosporine because of the sole structural difference at C-7. Therefore, a series of 7-O-alkyl derivatives of UCN-01 was synthesized and investigated. Interestingly, one of the compounds, the beta-methoxy derivative, showed 3-fold greater potency and 17-fold more selective inhibitory activity against protein kinase C than did UCN-01.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::4cc9747919db5fa06c44c3274efb4028 https://pubmed.ncbi.nlm.nih.gov/2262903 Zobrazit plný text záznamu