title: Kinesin spindle protein inhibitors in cancer: a patent review (2008 - present).
abstract: BACKGROUND
  Inhibition of kinesin spindle protein (KSP) has emerged as a novel and validated therapeutic strategy against cancers. A lot of new KSP inhibitors have been identified in recent years and some of them have entered clinical trials. This may provide more selections in future cancer therapy.
  
  
  METHODS
  In the present review, the authors will describe the most recent classes of KSP inhibitors by reviewing about 96 literatures in which 24 patent applications were included from 2008 to now.
  
  
  CONCLUSIONS
  Many new KSP inhibitors have been discovered that act either by binding in an allosteric site of KSP or by ATP competitive inhibition. There are several ATP non-competitive KSP inhibitors entering clinical investigation. Although they were both well tolerated and showed acceptable pharmacokinetic profiles, limited clinical response was always the problem. Mutation of the binding pocket was also a hindrance in the development of these allosteric inhibitors. The appearance of ATP competitive KSP inhibitors was considered to be able to overcome mutation-mediated resistance to the allosteric inhibitors, which could be a new approach for the development of novel KSP inhibitors.
authors: China Pharmaceutical University, Department of Medicinal Chemistry and Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization , Nanjing 210009 , China.
authors: Cheng
authors: C
authors: Jiang
authors: Qidong
authors: Q
authors: You
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000495:Allosteric Site; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001667:Binding, Competitive; D002986:Clinical Trials as Topic; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010330:Patents as Topic
chemical_list: D000970:Antineoplastic Agents; C470243:KIF11 protein, human; D000255:Adenosine Triphosphate; D016547:Kinesins