An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor

Clin Exp Pharmacol Physiol. 2016 Jun;43(6):585-601. doi: 10.1111/1440-1681.12571.


Human Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation. AURKA has been found to be overexpressed in various solid and haematological cancers and has been linked with poor prognosis. Its important role in cancer initiation, growth, and metastasis has brought the focus to search for potent and selective AURKA inhibitors for cancer treatment. MLN8237, also known as alisertib, is one selective AURKA inhibitor that has shown remarkable anticancer effects in preclinical studies. Alisertib exhibits favourable pharmacokinetic properties. Alisertib has generally showed good partial response rates of 4-52% and good safety profiles in Phase I and II trials when it is solely administered as well as combined with cytotoxic chemotherapeutic drugs. Recently, the multicentre, randomized Phase III study of alisertib in patients with relapsed or refractory peripheral T-cell lymphoma has been discontinued due to unsatisfactory efficacy. The low risk of side effects, accessibility, and effectiveness of alisertib makes it a new promising anticancer therapy and further mechanistic and clinical studies are warranted.

Keywords: Aurora kinase A; Aurora kinase inhibitor; alisertib; apoptosis; autophagy; cancer therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Aurora Kinase A / antagonists & inhibitors*
  • Aurora Kinase A / chemistry
  • Aurora Kinase A / metabolism*
  • Binding Sites / physiology
  • Clinical Trials as Topic / methods
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Structure, Secondary


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Aurora Kinase A