Document Report Card

ID: ALA2086329

Journal: ACS Med Chem Lett

Title: Design and synthesis of potent, selective inhibitors of matriptase.

Authors: Colombo E, Désilets A, Duchêne D, Chagnon F, Najmanovich R, Leduc R, Marsault E.

Abstract: Matriptase is a member of the type II transmembrane serine protease family. Several studies have reported deregulated matriptase expression in several types of epithelial cancers, suggesting that matriptase constitutes a potential target for cancer therapy. We report herein a new series of slow, tight-binding inhibitors of matriptase, which mimic the P1-P4 substrate recognition sequence of the enzyme. Preliminary structure-activity relationships indicate that this benzothiazole-containing RQAR-peptidomimetic is a very potent inhibitor and possesses a good selectivity for matriptase versus other serine proteases. A molecular model was generated to elucidate the key contacts between inhibitor 1 and matriptase.

CiteXplore: 24900505

DOI: 10.1021/ml3000534