UCN‐01, an anti‐tumor drug, is a selective inhibitor of the conventional PKC subfamily

Abstract

A selective PKC inhibitor, UCN‐01, was shown to exhibit anti‐tumor activity in vitro and in vivo. We investigated UCN‐01 with respect to isozyme‐specific PKC inhibition using purified recombinant or rabbit brain PKC isozymes, cPKCα, β and γ, nPKCδ, ϵ and ν, and aPKCζ. Of the PKC isozymes examined, cPKCα was inhibited by UCN‐01 most effectively (K _i = 0.44 nM), suggesting cPKCα is the prime candidate for the physiological target of UCN‐01. The K _i values of UCN‐01 estimated from Dixon plots for cPKC isozymes are approximately 1 nM, whereas the K _i values for nPKC isozymes are about 20 nM. Moreover, the K _i value for aPKCζ is 3.8 μM. Thus, UCN‐01 discriminates between PKC subfamilies. In addition, the inhibitory effects of staurosporine, H7, and calphostin C on aPKCζ were examined and compared with those for cPKCα.