Balicatib

Balicatib is an inhibitor of cathepsin K with IC50 value of 1.4nM.Balicatib is highly selective against cathepsin K over cathepsin B, L and S in the in vitro enzyme assay. However, the selectivity is not so high in cell-based enzyme assay. The lysosomotropic character of balicatib results in its accumulation in lysosomes and the subsequent nonselective off-target effects. The off-target effects also cause the skin adverse events of balicatib. As a cathepsin K inhibitor, balicatib is developed for osteoporosis. It has been reported to reduce the biochemical markers of bone resorption and increase bone mineral density in ovariectomized monkeys. (In Vitro) :Balicatib (0-10 μM) shows less than 1.5-fold accumulation of Type I collagen at concentrations up to 10 μM in human dermal fibroblasts. (In Vivo) :Balicatib (0, 3, 10, 50 mg/kg; Oral gavage; twice daily for 18 months) partially prevented ovariectomyinduced changes in bone mass, inhibited bone turnover at most sites, and had an stimulatory effect on periosteal bone formation in cynomolgus monkeys.