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Characterization of novel inhibitors of cyclin-dependent kinases.

Abstract：

:In epithelial cells progression through the G1 phase of the cell cycle and preparing the cell for the S phase is regulated by cyclin D1-cdk4. Cells that express the retinoblastoma protein (pRb) are dependent on cyclin D1-cdk4 activity for their proliferation while cells that do not express pRb are not. Overexpression of cyclin D1 and/or cdk4, and loss of expression of p16 (the natural inhibitor of cyclin D1-cdk4 activity), have been implicated in several cancers. These data suggest that the aberrant activity of cyclin D1-cdk4 correlates with the tumor phenotype. Hence, blocking cyclin D1-cdk4 activity may prove to be an effective anticancer therapy for pRb(+) tumors. In this paper, we report the identification of four novel compounds that selectively inhibit cyclin D1-cdk4 activity to various degrees. We further demonstrate that two of these compounds also selectively inhibit the target, pRb(+) tumor cells. The implications of these discoveries and their utility as anticancer agents are discussed.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kent LL,Hull-Campbell NE,Lau T,Wu JC,Thompson SA,Nori M

doi

10.1006/bbrc.1999.0891

subject

Has Abstract

pub_date

1999-07-14 00:00:00

pages

768-74

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(99)90891-4

journal_volume

260

pub_type

杂志文章

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