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Development of a highly selective c-Src kinase inhibitor.

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.

SUBMITTER: Brandvold KR

PROVIDER: S-EPMC3423592 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Development of a highly selective c-Src kinase inhibitor.

Brandvold Kristoffer R KR Steffey Michael E ME Fox Christel C CC Soellner Matthew B MB

ACS chemical biology 20120604 8

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 select ...[more]

PMID: 22594480

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