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ACS Chem Biol. 2012 Aug 17;7(8):1393-8. doi: 10.1021/cb300172e. Epub 2012 Jun 4.

Development of a highly selective c-Src kinase inhibitor.

Author information

1
Department of Medicinal Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109, USA.

Abstract

Generating highly selective probes to interrogate protein kinase function in biological studies remains a challenge, and new strategies are required. Herein, we describe the development of the first highly selective and cell-permeable inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves extension of traditional inhibitor design by appending functionality proposed to interact with the phosphate-binding loop of c-Src. Using our selective inhibitor, we demonstrate that selective inhibition is significantly more efficacious than pan-kinase inhibition in slowing the growth of cancer cells. We also show that inhibition of c-Abl kinase, an off-target of most c-Src inhibitors, promotes oncogenic cell growth.

PMID:
22594480
PMCID:
PMC3423592
DOI:
10.1021/cb300172e
[Indexed for MEDLINE]
Free PMC Article

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