Development of 'DFG-out' inhibitors of gatekeeper mutant kinases

  • Bioorg Med Chem Lett. 2012 Aug 15;22(16):5297-302. doi: 10.1016/j.bmcl.2012.06.036.
Hwan Geun Choi  1 ,  Jianming Zhang ,  Ellen Weisberg ,  James D Griffin ,  Taebo Sim ,  Nathanael S Gray
Affiliations
  • 1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
PMID: 22819762 DOI: 10.1016/j.bmcl.2012.06.036
Abstract

HG-7-85-01(22) and HG-7-86-01(26) are thiazolo[5,4-b]pyridine containing type II tyrosine kinase inhibitors with potent cellular activity against both wild-type and 'gatekeeper' mutant T315I- Bcr-Abl. Here we report on the 'hybrid design' concept and subsequent structure activity guided optimization efforts that resulted in the development of these inhibitors.

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