Cyclin-Dependent Kinase Modulators Studied at the NCI: Pre-Clinical and Clinical Studies

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 17, 14 Issues, 2017


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
ICCF-CNRS UMR 6296
Université Clermont Auvergne
Clermont-Ferrand
France


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Cyclin-Dependent Kinase Modulators Studied at the NCI: Pre-Clinical and Clinical Studies



Anti-Cancer Agents in Medicinal Chemistry, 3(1): 47-56.

Author(s): Edward A Sausville.

Affiliation: Developmental Therapeutics Program, National Cancer Institute, 6130 Executive Blvd., Rm. 8018, Rockville MD 20852, USA.

Abstract

The cyclin dependent kinases (CDKs) are key regulators of cell cycle progression. Lead compounds (from empirical anti-proliferative screening approaches) have been defined which modulate CDK function and have evidence of anti-proliferative activity in tissue culture systems and in some cases anti-tumor activity in vivo in conventional xenogaft models. Two of these, flavopiridol and UCN-01, have entered initial clinical testing. Flavopiridol is a “pan-CDK” inhibitor, with essentially equal potency in inhibiting all CDKs tested. The recent elucidation that in addition to cell cycle regulatory functions, CDK family members have been defined which regulate transcription, neuronal, and secretory function has increased the need for definition of CDK antagonists with greater selectivity. Novel purine, pyrimidine, and benzazepinone derivatives have been characterized in part

Keywords:

Cyclin-Dependent, Kinase Modulators, xenogaft, flavopiridol, glycoprotein.



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Article Details

Volume: 3
Issue Number: 1
First Page: 47
Last Page: 56
Page Count: 10
DOI: 10.2174/1568011033353560
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