Cathepsin K-lnhibitoren: praklinische und klinische Daten

摘要

Cathepsin K, a cysteine protease, is an essential en2yme in degradation of collagen type I. Since cathepsin K is relatively specific to osteoclasts, it represents a promising candidate for drug development. In the past decades, efforts have been made in developing highly potent, selective and orally applicable cathepsin K inhibitors. In contrast to balicatib and relacatib, whose drug development programmes were stopped due to cutaneous side-effects related to limited drug specificity, the more specific cathepsin K inhibitors odana-catib (ODN) and ONO-5334 have entered clinical trials. Odanacatib progressively increases bone mineral density (BMD) and decreases bone resorption markers in post-menopausal women with low BMD. Its clinical efficacy and safety was confirmed by several clinical studies but indicates that odanacatib is characterized by a resolution-of-effect with increases in bone resorption and rapid decreases in BMD following treatment discontinuation. A phase III fracture prevention study in postmenopausal women with osteoporosis is currently in the final phase.