Inhibitors of protein kinase C. 2. Substituted bisindolylmaleimides with improved potency and selectivity

PD Davis, LH Elliott, W Harris, CH Hill…

Index: Davis, Peter D.; Elliot, Lucy H.; Harris, William; Hill, Christopher H.; Hurst, Steven A.; et al. Journal of Medicinal Chemistry, 1992 , vol. 35, # 6 p. 994 - 1001

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Citation Number: 243

Abstract

A hypothetical mode of inhibition of protein kinase C (PKC) by the natural product staurosporine has been used as a basis for the design of substituted bisindolylmaleimides with improved potency over the parent compound. Structure-activity relationships were consistent with the interaction of a cationic group in the inhibitor with a carboxylate group in the enzyme, and the most potent compound had a Ki of 3 nM. The inhibitors were ...