title: Danusertib, an aurora kinase inhibitor.
abstract: BACKGROUND
  Drugs that interfere with the normal progression of mitosis belong to the most successful cytotoxic agents currently used for anticancer treatment. Aurora kinases are serine/threonine kinases that function as key regulators of mitosis and are frequently overexpressed in human cancers. The use of several small molecule aurora kinase inhibitors as potential anticancer therapeutic is being investigated. Danusertib (formerly PHA-739358) is a small ATP competitive molecule that inhibits aurora A, B and C kinases. Interestingly, danusertib also inhibits several receptor tyrosine kinases such as Abl, Ret, FGFR-1 and TrkA. These tyrosine kinases are involved in the pathogenesis of a variety of malignancies and the observed multi-target inhibition may increase the antitumor activity resulting in extending the indication. Danusertib was one of the first aurora kinase inhibitors to enter the clinic and has been studied in Phase I and II trials.
  
  
  METHODS
  This review provides an updated summary of preclinical and clinical experience with danusertib up to July 2011.
  
  
  CONCLUSIONS
  Future studies with danusertib should focus on the possibility of combining this agent with other targeted anticancer agents, chemotherapy or radiotherapy. As a single agent, danusertib may show more promise in the treatment of leukemias than in solid tumors.
authors.affiliation: Erasmus University Medical Center, Daniel den Hoed Cancer Center, Department of Medical Oncology, Groene Hilledijk 301, Rotterdam, the Netherlands. h.meulenbeld@erasmusmc.nl
authors.forename: Hielke J
authors.initials: HJ
authors.lastname: Meulenbeld
authors.forename: Ron Hj
authors.initials: RH
authors.lastname: Mathijssen
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: Maja Ja
authors.initials: MJ
authors.lastname: de Jonge
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011505:Protein-Tyrosine Kinases; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C523797:danusertib