Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization.

ABSTRACT:

Background

Overexpression or mutation of the epidermal growth factor receptor (EGFR) potently enhances the growth of many solid tumors. Tumor cells frequently display resistance to mechanistically-distinct EGFR-directed therapeutic agents, making it valuable to develop therapeutics that work by additional mechanisms. Current EGFR-targeting therapeutics include antibodies targeting the extracellular domains, and small molecules inhibiting the intracellular kinase domain. Recent studies have identified a novel prone extracellular tetrameric EGFR configuration, which we identify as a potential target for drug discovery.

Methods

Our focus is on the prone EGFR tetramer, which contains a novel protein-protein interface involving extracellular domain III. This EGFR tetramer is comp

SUBMITTER: Ramirez UD 

PROVIDER: S-EPMC4451962 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature