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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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Brandvold KR,Steffey ME,Fox CC,Soellner MB

doi

10.1021/cb300172e

subject

Has Abstract

pub_date

2012-08-17 00:00:00

pages

1393-8

issue

8

eissn

1554-8929

issn

1554-8937

journal_volume

7

pub_type

杂志文章

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