Balicatib is a potent and selective inhibitor of cathepsin K ,with 10-100 fold more potent in cell-based enzyme occupancy assays than against cathepsin B, L, and S.
Cathepsin K is a member of the papain family of cysteine proteases which is associated with osteopetrosis, impaired resorption of bone matrix, impaired processing of thyroglobulin and reduced release of thyroid hormone. Balicatib is a very potent and selective inhibitor of human cathepsin K, with a Ki value of 0.7 nM. 140 postmenopausal women administered of AAE-581 once a day orally (10-50 mg per day) showed successful reduced bone resorption and improved bone formation[3]. Balicatib treatment for 18 months in female cynomolgus monkeys (orally twice daily by nasogastric intubation, 10/30/50 mg/kg/day) partially prevented ovariectomy-induced changes in bone mass and inhibited cancellous bone turnover[4].
作用机制
Balicatib targets to lysosomes by conjugating with poly(ethylene glycol) polymers.
搜索
