Complexities in the development of cyclin-dependent kinase inhibitor drugs.
Abnormalities in the normal regulation of the cell cycle are a hallmark of neoplasia. Drugs directed against the cyclin-dependent kinases (CDKs), which govern the normal orderly progression through the cell cycle, have been proposed to address the pathogenic defect in tumors. Recently, CDK family members that do not regulate the cell cycle directly but instead influence transcription (CDK7, CDK8, and CDK9) and neuronal and secretory cell function (CDK5) have been described. Continued synthetic chemistry efforts have defined important new selective inhibitors of CDKs, and strategies directed at newly described CDK-related targets, such as transcription control, can now be envisaged. CDKs remain important and novel targets whose potential needs to be more fully explored, albeit in light of the newly emerging complexities of their cellular physiology.
Sausville
Edward A
EA
Developmental Therapeutics Program, National Cancer Institute, Executive Plaza North Room 8018, 6130 Executive Boulevard, Rockville, MD 20852, USA. sausville@nih.gov
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D016213:Cyclins; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases