Thor S Thorsen, Kenneth L Madsen, Nelson Rebola, Mette Rathje, Victor Anggono, Anders Bach, Irina S Moreira, Nicolai Stuhr-Hansen, Tino Dyhring, Dan Peters, Thijs Beuming, Richard Huganir, Harel Weinstein, Christophe Mulle, Kristian Strømgaard, Lars Christian B Rønn, Ulrik Gether
Proteins containing PSD-95/Discs-large/ZO-1 homology (PDZ) domains play key roles in the assembly and regulation of cellular signaling pathways and represent putative targets for new pharmacotherapeutics. Here we describe the first small-molecule inhibitor (FSC231) of the PDZ domain in protein interacting with C kinase 1 (PICK1) identified by a screening of approximately 44,000 compounds in a fluorescent polarization assay. The inhibitor bound the PICK1 PDZ domain with an affinity similar to that observed for endogenous peptide ligands (K(i) approximately 10...
January 5, 2010: Proceedings of the National Academy of Sciences of the United States of America