Cathepsin K inhibitors: emerging treatment options for osteoporosis

Excerpt

Cathepsin K belongs to the group of cysteine proteases; most members of this family are widely expressed throughout many tissues and are involved in protein degradation and extracellular matrix remodelling. Cathepsin K has a relatively restricted expression pattern; it is highly expressed in the cells responsible for bone resorption—the osteoclasts—and has a crucial role in the degradation of bone matrix, in particular type I collagen. In mice, the deficiency of cathepsin K leads to a high bone mass phenotype (“osteopetrosis”) that resembles pycnodysostosis in humans. The relevance of cathepsin K for bone is also underscored by the observation that overexpression of the enzyme results in a low bone mass/“osteoporotic” phenotype. The fundamental role of cathepsin K in bone resorption has led to the development of cathepsin K inhibitors for the treatment of diseases characterized by excessive bone degradation. Currently, several cathepsin K inhibitors are under preclinical or clinical investigation for indications such as bone metastases, rheumatoid arthritis or osteoporosis [1]. …