Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C - PubMed (original) (raw)

Comparative Study

. 1993 Sep 1;294 ( Pt 2)(Pt 2):335-7.

doi: 10.1042/bj2940335.

Affiliations

• PMID: 8373348
• PMCID: PMC1134458
• DOI: 10.1042/bj2940335

Comparative Study

Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C

S E Wilkinson et al. Biochem J. 1993.

Abstract

The protein kinase C (PKC) family of isoenzymes is believed to mediate a wide range of signal-transduction pathways in many different cell types. A series of bisindolylmaleimides have been evaluated as inhibitors of members of the conventional PKC family (PKCs-alpha, -beta, -gamma) and of a representative of the new, Ca(2+)-independent, PKC family, PKC-epsilon. In contrast with the indolocarbazole staurosporine, all the bisindolylmaleimides investigated showed slight selectivity for PKC-alpha over the other isoenzymes examined. In addition, bisindolylmaleimides bearing a conformationally restricted side-chain were less active as inhibitors of PKC-epsilon. Most noticeable of these was Ro 32-0432, which showed a 10-fold selectivity for PKC-alpha and a 4-fold selectivity for PKC-beta I over PKC-epsilon.

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