PT  - JOURNAL ARTICLE
AU  - I Takahashi
AU  - E Kobayashi
AU  - H Nakano
AU  - C Murakata
AU  - H Saitoh
AU  - K Suzuki
AU  - T Tamaoki
TI  - Potent selective inhibition of 7-O-methyl UCN-01 against protein kinase C.
DP  - 1990 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1218--1221
VI  - 255
IP  - 3
4099  - http://jpet.aspetjournals.org/content/255/3/1218.short
4100  - http://jpet.aspetjournals.org/content/255/3/1218.full
SO  - J Pharmacol Exp Ther1990 Dec 01; 255
AB  - 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.