组织蛋白酶K抑制剂Odanacatib的研究进展

New approach for osteoporosis treatment:cathepsin K inhibitor,Odanacatib

组织蛋白酶K是一种在破骨细胞高表达的溶酶体蛋白酶,在骨胶原的降解过程中发挥关键作用。临床前研究证实,组织蛋白酶K抑制剂可以逆转去卵巢动物的骨量流失,恢复其骨强度。Odanacatib是一种高度选择性的组织蛋白酶K抑制剂,几乎不产生硬斑病样皮肤病变。一项为期3年、对绝经后骨量减少或骨质疏松症的临床研究发现,较之安慰剂组,Odanacatib治疗组的骨密度明显升高,治疗效果与目前广泛应用的双膦酸盐等抗吸收药物相当,除此之外还具有不抑制骨形成的优点。

Cathepsin K is a lysosomal protease that is specifically expressed in osteoclasts and plays an important role in the degradation of bone collagen. Cathepsin K inhibitors have been shown in preclinical studies to reverse ovar- iectomy induced bone loss and to restore bone strength. Odanacatib is a highlly selective cathepsin K inhibitor, structurally distinct from other inhibitors that occasionally induced ＂morphea-like＂ skin changes. In a 36-month clinical study with postmenopausal osteopenia or osteoporosis, odanacatib showed a significant increase in BMD compared with placebo and a similar magnitude of suppression on bone resorption compared with the current well known anti-resorptive agents, bisphosphonates, but with little or no suppression on bone formation.