Characterization of a highly selective inhibitor of the Aurora kinases

Fleur M. Ferguson, Zainab M. Doctor, Apirat Chaikuad, Taebo Sim, Nam Doo Kim, Stefan Knapp, Nathanael S. Gray

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aurora kinases play an essential role in mitosis and cell cycle regulation. In recent years Aurora kinases have proved popular cancer targets and many inhibitors have been developed. The majority of these clinical candidates are multi-targeted, rendering them inappropriate as tools for studying Aurora kinase mediated signaling. Here we report discovery of a highly selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4). The X-ray co-crystal structure of Aurora A in complex with compound 2 is reported, and provides insights into the structural determinants of ligand binding and selectivity.

Original languageEnglish
Pages (from-to)4405-4408
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number18
DOIs
Publication statusPublished - 2017 Sep 15

Keywords

  • Aurora kinase
  • Cancer
  • Mitosis
  • Pan-Aurora inhibitor
  • Selective kinase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Ferguson, F. M., Doctor, Z. M., Chaikuad, A., Sim, T., Kim, N. D., Knapp, S., & Gray, N. S. (2017). Characterization of a highly selective inhibitor of the Aurora kinases. Bioorganic and Medicinal Chemistry Letters, 27(18), 4405-4408. https://doi.org/10.1016/j.bmcl.2017.08.016