Drugging cell cycle kinases in cancer therapy.

  • Blagden S
  • de Bono J
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Abstract

Cell cycle kinases are comprised of cyclin-dependent kinases (Cdks), non-Cdk kinases such as Plk-1 and Aurora and checkpoint proteins such as Chk1 and Chk2. Though ubiquitous to dividing cells, many cell cycle kinases are amplified or over-expressed in malignancy and are potential targets for anti-cancer therapies. Cdk inhibiting drugs (such as flavopiridol, UCN-01, E7070, R-Roscovitine and BMS-387032) have shown preclinical and clinical anticancer activity. However, many of these agents are promiscuous and undiscerning, targeting other non-cell cycle kinases and affecting normal cells, thereby causing significant toxicity. To overcome this, a new generation of Cdk inhibitors are in development with greater target specificity, as well as others that inhibit non-Cdk cell cycle kinases, both directly and indirectly. The outcome of early clinical trials involving these agents is awaited, but these certainly represent a promising new area of anticancer drug development.

Author-supplied keywords

  • Adenosine Triphosphate
  • Adenosine Triphosphate: metabolism
  • Animals
  • Antineoplastic Agents
  • Antineoplastic Agents: therapeutic use
  • Binding Sites
  • Cyclin-Dependent Kinases
  • Cyclin-Dependent Kinases: antagonists & inhibitors
  • Cyclin-Dependent Kinases: physiology
  • Flavonoids
  • Flavonoids: therapeutic use
  • Humans
  • Neoplasms
  • Neoplasms: drug therapy
  • Oxazoles
  • Oxazoles: therapeutic use
  • Piperidines
  • Piperidines: therapeutic use
  • Protein Kinase Inhibitors
  • Protein Kinase Inhibitors: therapeutic use
  • Purines
  • Purines: therapeutic use
  • Staurosporine
  • Staurosporine: analogs & derivatives
  • Staurosporine: therapeutic use
  • Sulfonamides
  • Sulfonamides: therapeutic use
  • Thiazoles
  • Thiazoles: therapeutic use

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Authors

  • S Blagden

  • J de Bono

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