Structural conservation in band 4.1, ezrin, radixin, moesin (FERM) domains as a guide to identify inhibitors of the proline-rich tyrosine kinase 2.

ABSTRACT: The nonreceptor focal adhesion kinases FAK and Pyk2 play a central role in the regulation of glioma cell proliferation and migration, making them attractive targets to improve clinical outcome. Noncatalytic targeting represents a novel approach to regulate the activity of these tyrosine kinases. A combination of site directed mutagenesis and molecular modeling was used to identify compounds that target the F3 module of the Pyk2 FERM domain. A protein pharmacophore model for the Pyk2 FERM/F3 module, generated utilizing the structural conservation of ligand-bound FERM domains with known 3D structures, was used to search the LeadQuest compound library. Compounds compliant with the model were tested for their ability to inhibit the binding of a monoclonal antibody that maps to a functional sit

SUBMITTER: Meurice N 

PROVIDER: S-EPMC3178892 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature