Progress in the Development of Selective Inhibitors of Aurora Kinases

Authors: Mortlock, Andrew¹; Keen, Nicholas J.¹; Jung, Frederic H.¹; Heron, Nicola M.¹; Foote, Kevin M.¹; Wilkinson, Robert¹; Green, Stephen¹

Source: Current Topics in Medicinal Chemistry, Volume 5, Number 2, April 2005 , pp. 199-213(15)

Publisher: Bentham Science Publishers

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Abstract:

Errors in the mitotic process are thought to be one of the principal sources of the genetic instability that hallmarks cancer. Unsurprisingly, many of the proteins that regulate mitosis are aberrantly expressed in tumour cells when compared to their normal counterparts. These may represent a good source of targets for the development of novel anticancer agents. The Aurora kinases represent one such family of mitotic regulators.

In recent years there has been intense interest in both understanding the role of the Aurora kinases in cell cycle regulation and also in developing small molecule inhibitors as potential novel anti-cancer drugs. With several companies now starting to take Aurora kinase inhibitors into clinical development, the time is right to review the medicinal chemistry contribution to developing the field, in particular to review the increasingly broad range of small molecule inhibitors with activity against this kinase family.

Keywords: aurora a; aurora b; cell cycle; mitosis; polyploidy; centrosome; kinase inhibition; histone h3; cytokinesis

Document Type: Review article

DOI: 10.2174/1568026053507651

Affiliations: 1: AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, UK, SK10 4TG.

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