2. Academic Validation
  3. Identification of novel, potent and selective inhibitors of Polo-like kinase 1

Identification of novel, potent and selective inhibitors of Polo-like kinase 1

  • Bioorg Med Chem Lett. 2012 Jan 15;22(2):1247-50. doi: 10.1016/j.bmcl.2011.11.052.
Shaoqing Chen 1,  David Bartkovitz,  Jianping Cai,  Yi Chen,  Zhi Chen,  Xin-Jie Chu,  Kang Le,  Nam T Le,  Kin-Chun Luk,  Steve Mischke,  Goli Naderi-Oboodi,  John F Boylan,  Tom Nevins,  Weiguo Qing,  Yingsi Chen,  Peter M Wovkulich
Affiliations

Affiliation

  • 1 Discovery Chemistry, Hoffmann-La Roche Inc., Pharma Research & Early Development, Small Molecule Research, 340 Kingsland Street, Nutley, NJ 07110, United States. [email protected]
PMID: 22172702 DOI: 10.1016/j.bmcl.2011.11.052
Abstract

A series of pyrimidodiazepines was identified as potent Polo-like kinase 1 (PLK1) inhibitors. The synthesis and SAR are discussed. The lead compound 7 (RO3280) has potent inhibitory activity against PLK1, good selectivity against other kinases, and excellent in vitro cellular potency. It showed strong antitumor activity in xenograft mouse models.

Figures
Products