Cathepsin K as a target for the treatment of osteoporosis

Cathepsin K is a recently discovered member of the papain superfamily of cysteine proteinases. This enzyme is highly expressed in human osteoclast cells where it plays an important role in the resorption processes in normal bone remodelling. The importance of cathepsin K in osteoclast-mediated resorption of the bone matrix provides a rationale for the design of inhibitors of cathepsin K as potential drugs for the treatment of diseases of excess bone remodelling such as osteoporosis. Successful application of modem methods of drug discovery, including genomics and structure-based methods of drug design, has resulted in the identification of this previously unknown therapeutic target and the rapid elucidation of novel, potent and selective inhibitors of human osteoclast cathepsin K. Several classes of inhibitors of cathepsin K that have been reported in the published literature and in recent patent filings are described in this review.