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Peptidomimetic Inhibitors of Cathepsin K

[ Vol. 10 , Issue. 7 ]


W. Cameron Black   Pages 745 - 751 ( 7 )


Cathepsin K (Cat K) is the primary enzyme involved in Type I collagen degradation in bone resorption. The development of a Cat K inhibitor should provide an effective treatment for osteoporosis. Key components of a clinically viable inhibitor are oral bioavailability, high selectivity over related cathepsins, and a covalent, reversible warhead to bind to the active site cysteine of the enzyme. This article reviews recent advances in the design of inhibitors derived from peptidic leads that contain either a ketone or nitrile electrophile. Three of these compounds have progressed into clinical trials and one, odanacatib (5), is currently in Phase III studies for the treatment of post-menopausal osteoporosis.


Osteoporosis, cathepsin K, cysteine protease, lysosomotropism, selective inhibitor, peptidomimetic, bone resorption


Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, Que., Canada H9R 4P8.

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