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

• Published in: FEBS letters 1995-02, Vol.359 (2), p.259-261
• Main Authors: Mizuno, Keiko, Noda, Kumi, Ueda, Yoshihiko, Hanaki, Hisao, Saido, Takaomi C., Ikuta, Tohgo, Kuroki, Toshio, Tamaoki, Tatsuya, Hirai, Syu-ichi, Osada, Shin-ichi, Ohno, Shigeo
• Format: Article
• Language: English
• Subjects: Alkaloids - pharmacology; Amino Acid Sequence; Animals; Antineoplastic Agents - pharmacology; aPKC; atypical PKC; Brain - enzymology; conventional PKC; cPKC; Isoenzymes - antagonists & inhibitors; Molecular Sequence Data; novel PKC; nPKC; PKC; PKC inhibitor; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Rabbits; Recombinant Proteins - antagonists & inhibitors; Staurosporine - analogs & derivatives; UCN-01
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00042-8

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.