Progress in the evaluation of CDK inhibitors as anti-tumor agents.
The increase in understanding of the events of cell growth and division has enabled the development of pharmacological agents inhibiting key regulatory proteins, with the cyclin dependent kinases (CDKs) representing a major area of interest. Owing to multiple CDK variants having cell cycle and transcriptional regulatory roles and difficulties in generating selective inhibitors, the prospects for drug discovery and development are complex. Numerous CDK inhibitors with differing mechanistic profiles are currently being preclinically and clinically evaluated but have not as of yet resulted in a drug approval. The major issues of CDK inhibition related to current understanding from genetic studies and also from observed anti-tumor efficacy of representative compounds are discussed in this review.
McInnes
Campbell
C
Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA. mcinnes@sccp.sc.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases