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, cPKC alpha, beta and gamma, nPKC delta, epsilon and eta, and a PKC zeta. Of the PKC isozymes examined, cPKC alpha was inhibited by UCN-01 most effectively (Ki = 0.44 nM), suggesting cPKC alpha is the prime candidate for the physiological target of UCN-01. The Ki values of UCN-01 estimated from Dixon plots for cPKC isozymes are approximately 1 nM, whereas the Ki values for nPKC isozymes are about 20 nM. Moreover, the Ki value for aPKC zeta is 3.8 microM. Thus, UCN-01 discriminates between PKC subfamilies. In addition, the inhibitory effects of staurosporine, H7, and calphostin C on aPKC zeta were examined and compared with those for cPKC alpha.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Mizuno K,Noda K,Ueda Y,Hanaki H,Saido TC,Ikuta T,Kuroki T,Tamaoki T,Hirai S,Osada S

doi

10.1016/0014-5793(95)00042-8

subject

Has Abstract,Author List Incomplete

pub_date

1995-02-13 00:00:00

pages

259-61

issue

2-3

eissn

0014-5793

issn

1873-3468

journal_volume

359

pub_type

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