Cathepsin K as a target for the treatment of osteoporosis

Cathepsin K is a recently discovered member of the papain superfamily of cy steine proteinases. This enzyme is highly expressed in human osteoclast cel ls where it plays an important role in the resorption processes in normal b one remodelling. The importance of cathepsin K in osteoclast-mediated resor ption 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 b one remodelling such as osteoporosis. Successful application of modem metho ds of drug discovery, including genomics and structure-based methods of dru g design, has resulted in the identification of this previously unknown the rapeutic target and the rapid elucidation of novel, potent and selective in hibitors of human osteoclast cathepsin K. Several classes of inhibitors of cathepsin K that have been reported in the published literature and in rece nt patent filings are described in this review.