Novel inhibitors of a Grb2 SH3C domain interaction identified by a virtual screen.
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ABSTRACT:
SUBMITTER: Simister PC
PROVIDER: S-EPMC3594550 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Publications
Novel inhibitors of a Grb2 SH3C domain interaction identified by a virtual screen.
Simister Philip C PC Luccarelli James J Thompson Sam S Appella Daniel H DH Feller Stephan M SM Hamilton Andrew D AD
Bioorganic & medicinal chemistry 20121027 14
The adaptor protein Grb2 links cell-surface receptors, such as Her2, to the multisite docking proteins Gab1 and 2, leading to cell growth and proliferation in breast and other cancers. Gab2 interacts with the C-terminal SH3 domain (SH3C) of Grb2 through atypical RxxK motifs within polyproline II or 310 helices. A virtual screen was conducted for putative binders of the Grb2 SH3C domain. Of the top hits, 34 were validated experimentally by surface plasmon resonance spectroscopy and isothermal tit ...[more]
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