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ACS Med Chem Lett. 2012 Apr 11;3(7):530-4. doi: 10.1021/ml3000534. eCollection 2012 Jul 12.

Design and synthesis of potent, selective inhibitors of matriptase.

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Department of Pharmacology and Department of Biochemistry, Faculty of Medicine and Health Sciences, Université de Sherbrooke , 3001 12e Avenue Nord, Sherbrooke PQ, J1H5N4, Canada.


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.


matriptase; slow tight-binding inhibitor; type II transmembrane serine protease

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