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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Peptidomimetic Inhibitors of Cathepsin K

Author(s): W. Cameron Black

Volume 10, Issue 7, 2010

Page: [745 - 751] Pages: 7

DOI: 10.2174/156802610791113450

Price: $65


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.

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

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