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Cell cycle kinases are comprised of cyclin-dependent kinases (Cdks), non-Cdk kinases such as Plk-1 and Aurora and checkpoint proteins such as Chk1 and Chk2. Though ubiquitous to dividing cells, many cell cycle kinases are amplified or over-expressed in malignancy and are potential targets for anti-cancer therapies. Cdk inhibiting drugs (such as flavopiridol, UCN-01, E7070, R-Roscovitine and BMS-387032) have shown preclinical and clinical anticancer activity. However, many of these agents are promiscuous and undiscerning, targeting other non-cell cycle kinases and affecting normal cells, thereby causing significant toxicity. To overcome this, a new generation of Cdk inhibitors are in development with greater target specificity, as well as others that inhibit non-Cdk cell cycle kinases, both directly and indirectly. The outcome of early clinical trials involving these agents is awaited, but these certainly represent a promising new area of anticancer drug development.

Type

Journal article

Journal

Curr Drug Targets

Publication Date

05/2005

Volume

6

Pages

325 - 335

Keywords

Adenosine Triphosphate, Animals, Antineoplastic Agents, Binding Sites, Cyclin-Dependent Kinases, Flavonoids, Humans, Neoplasms, Oxazoles, Piperidines, Protein Kinase Inhibitors, Purines, Roscovitine, Staurosporine, Sulfonamides, Thiazoles