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

Hwan Geun Choi, Jianming Zhang, Ellen Weisberg, James D. Griffin, Taebo Sim, Nathanael S. Gray

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5297-5302
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number16
DOIs
Publication statusPublished - 2012 Aug 15

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Keywords

  • Gatekeeper mutant
  • Kinase inhibitor
  • T315I Bcr-Abl
  • Thiazolo[5,4-b]pyridine
  • Type II inhibitor

ASJC Scopus subject areas

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

Cite this

Choi, H. G., Zhang, J., Weisberg, E., Griffin, J. D., Sim, T., & Gray, N. S. (2012). Development of 'DFG-out' inhibitors of gatekeeper mutant kinases. Bioorganic and Medicinal Chemistry Letters, 22(16), 5297-5302. https://doi.org/10.1016/j.bmcl.2012.06.036