Chemical inhibitors of cyclin-dependent kinases

The eukaryotic cell division cycle is regulated by a family of protein kinases, the cyclin-dependent kinases (cdk's), constituted of at least two subunits, a catalytic subunit (cdk1-7) associated with a regulatory subunit (cyclin A-H). Transient activation of cdk's is responsible for transition through the different phases of the cell cycle. Major abnormalities of cdk's expression and regulation have been described in human tumours. Enzymatic screening is starting to uncover chemical inhibitors of cdk's with anti-mitotic activities. This review summarizes our knowledge of these first inhibitors, their mechanism of action, their effects on the cell cycle, and discusses the potential of such type of inhibitors as anti-tumour agents.