2. Academic Validation
  3. Discovery of selective aminothiazole aurora kinase inhibitors

Discovery of selective aminothiazole aurora kinase inhibitors

  • ACS Chem Biol. 2008 Mar 20;3(3):180-92. doi: 10.1021/cb700200w.
Carsten B Andersen 1,  Yongqin Wan,  Jae W Chang,  Blake Riggs,  Christian Lee,  Yi Liu,  Fabio Sessa,  Fabrizio Villa,  Nicholas Kwiatkowski,  Melissa Suzuki,  Laxman Nallan,  Rebecca Heald,  Andrea Musacchio,  Nathanael S Gray
Affiliations

Affiliation

  • 1 Department of Biological Chemistry, Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA.
PMID: 18307303 DOI: 10.1021/cb700200w
Abstract

Aurora family kinases regulate important events during Mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 A cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora Kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.

Figures
Products