The use of CDK inhibitors in oncology: a pharmaceutical perspective.
To date dozens of pharmacophores with CDK-inhibitory properties have been discovered and the first compounds possessing such activity are now under clinical evaluation. Because the real therapeutic utility of these agents should be able to be assessed in the foreseeable future, it is unfortunate that CDK biology remains a moving target. Until recently is has been held that inhibiting CDK2, presumed master of the 10 known CDK isoforms, should be most beneficial in terms of achieving potent and selective antiproliferative effects in transformed cells. Recent findings, however, suggest that CDK2 may not be the key cell cycle player previously assumed, after all. It has also now become clear that CDKs have functions in physiological processes other than coordination of cell cycle progression, particularly regulation of DNA transcription. The implications of these new biological insights for the discovery and development of CDK inhibitors in oncology are discussed.
Fischer
Peter M
PM
Cyclacel Limited, Dundee, Scotland, UK. pfischer@cyclacel.com
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D017891:Pharmacoepidemiology / Q000639:trends*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases