CDK inhibitors in clinical development for the treatment of cancer

Expert Opin Investig Drugs. 2003 Jun;12(6):955-70. doi: 10.1517/13543784.12.6.955.

Abstract

Cyclin-dependent protein kinases (CDKs) are key regulators of the cell division cycle, whose various checkpoints proliferating cells must traverse. Since CDK deregulation, either through direct or indirect means, is found in most cancer cells, pharmacological CDK inhibition has become an attractive strategy towards mechanism-based and non-genotoxic therapies in oncology. Over the last decade, discovery and lead optimisation efforts have provided a wealth of potential drug candidate molecules capable of inhibiting CDKs, blocking cell-cycle progression, modulating transcription and inducing apoptosis selectively in cancer cells. However, only few such agents have as yet reached clinical evaluation. Here, the preclinical and clinical results obtained so far with flavopiridol (L868275, HMR1275; Aventis), 7-hydroxystaurosporine (UCN-01, KW-2401; Kyowa Hakko Kogyo) and roscovitine (R-roscovitine, CYC202; Cyclacel) are summarised. Furthermore, the potential for monotherapy and applications in combination with existing drugs are discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic / methods
  • Clinical Trials as Topic / statistics & numerical data*
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology

Substances

  • Enzyme Inhibitors
  • Cyclin-Dependent Kinases