Progress in the development of selective inhibitors of Aurora kinases.
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 anti-cancer 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.
Mortlock
Andrew
A
Cancer and Infection Research Area, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, UK, SK10 4TG. andrew.mortlock@astrazeneca.com
Keen
Nicholas J
NJ
Jung
Frederic H
FH
Heron
Nicola M
NM
Foote
Kevin M
KM
Wilkinson
Robert
R
Green
Stephen
S
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D064127:Aurora Kinases; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases