A small-molecule inhibitor, 5'-O-tritylthymidine, targets FAK and Mdm-2 interaction, and blocks breast and colon tumorigenesis in vivo.

ABSTRACT: Focal Adhesion Kinase (FAK) is overexpressed in many types of tumors and plays an important role in survival. We developed a novel approach, targeting FAK-protein interactions by computer modeling and screening of NCI small molecule drug database. In this report we targeted FAK and Mdm-2 protein interaction to decrease tumor growth. By macromolecular modeling we found a model of FAK and Mdm-2 interaction and performed screening of > 200,000 small molecule compounds from NCI database with drug-like characteristics, targeting the FAK-Mdm-2 interaction. We identified 5';-O-Tritylthymidine, called M13 compound that significantly decreased viability in different cancer cells. M13 was docked into the pocket of FAK and Mdm-2 interaction and was directly bound to the FAK-N terminal domain by Forte

SUBMITTER: Golubovskaya VM 

PROVIDER: S-EPMC3625481 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature