Recent progress in the identification and clinical evaluation of inhibitors of the mitotic kinesin KSP.
Kinesin spindle protein (KSP), a mitotic kinesin responsible for bipolar spindle establishment and maintenance, is currently the target of intense research for the development of novel anticancer therapeutics. Several inhibitors of KSP have progressed into clinical trials and many others are in preclinical development. A majority of these inhibitors are ATP-uncompetitive and bind in an allosteric loop L5 binding pocket, but recently, inhibitors with an alternative mechanism of action (ATP-competitive) have also been identified and characterized. In this review, an update of the clinical trial results with ATP-uncompetitive KSP inhibitors is provided and recent progress in the identification of additional KSP inhibitors is discussed.
Knight
Steven D
SD
Department of Medicinal Chemistry, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA. steven.d.knight@gsk.com
Parrish
Cynthia A
CA
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D016547:Kinesins