Manako Junichiro
Clinical Development Planning I-II, Ono Pharmaceutical Company Limited.
Clin Calcium. 2011 Jan;21(1):64-9.
ONO-5334, an orally-administered low-molecular compound, is a selective synthetic inhibitor of cathepsin K which is specifically expressed in osteoclasts and has a critical role in bone-collagen degradation. ONO-5334 is being developed by Ono Pharmaceutical Co., Ltd. as a possible therapeutic agent for osteoporosis. ONO-5334 has been shown to prevent the decrease in bone mineral density (BMD) in the ovariectomized cynomolgus monkey osteoporosis model. In a 12-month clinical study with postmenopausal osteopenia or osteoporosis, ONO-5334 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. There were no clinically relevant safety concerns identified in this study. Whether this mechanism of action may result in more potent anti-fracture efficacy accompanied by better bone quality in long term use of ONO-5334 is of significant interest.
ONO - 5334是一种口服的低分子化合物，是组织蛋白酶K的选择性合成抑制剂，组织蛋白酶K在破骨细胞中特异性表达，在骨胶原降解中起关键作用。小野制药株式会社正在将ONO - 5334开发为一种可能用于治疗骨质疏松症的药物。在去卵巢食蟹猴骨质疏松模型中，ONO - 5334已被证明可预防骨矿物质密度（BMD）的降低。在一项针对绝经后骨质减少或骨质疏松症的为期12个月的临床研究中，与安慰剂相比，ONO - 5334使BMD显著增加，并且与目前广为人知的抗吸收药物双膦酸盐相比，对骨吸收的抑制程度相似，但对骨形成几乎没有抑制作用。在该研究中未发现临床相关的安全问题。长期使用ONO - 5334时，这种作用机制是否可能导致更有效的抗骨折疗效以及更好的骨质，这一点备受关注。
