Aurora kinase targeted therapeutics in oncology: Past, present and future

Daruka Mahadevan, Sunni Beeck

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Aurora A, B and C are a family of serine-threonine protein kinases that regulate distinct functions of the mitotic phase of the cell cycle. All three Auroras are overexpressed in human cancers with an associated polyploid phenotype. Crystal structures of Aurora A or B with bound small molecular inhibitors have provided detailed insight of the active site, mode of binding and hotspots for developing resistance through point mutations. Structural studies have aided fragment-based rational drug discovery of Aurora inhibitors, including compounds specific for Aurora A or B. Aurora inhibitors have excellent antitumor activity in rodent models of cancer. At present, Aurora inhibitors are being evaluated in Phase I trials. The future holds promise for rational combinations in both solid and hematological malignancies.

Original languageEnglish (US)
Pages (from-to)1011-1026
Number of pages16
JournalExpert Opinion on Drug Discovery
Volume2
Issue number7
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Keywords

  • Aneuploidy
  • Aurora kinase
  • Cancer
  • Cell cycle
  • Mitotic phase
  • Small molecular inhibitor

ASJC Scopus subject areas

  • Drug Discovery

Fingerprint Dive into the research topics of 'Aurora kinase targeted therapeutics in oncology: Past, present and future'. Together they form a unique fingerprint.

Cite this