Department of Pharmacology, Wayne State University School of Medicine, 540 E. Canfield, Rm 6304, Detroit, MI 48201, USA.
Future Med Chem. 2009 Apr;1(1):21-34. doi: 10.4155/fmc.09.4.
Until fairly recently, cathepsin K was recognized solely as a bone-resorbing enzyme expressed selectively in the osteoclast. Evidence of its requirement for normal bone remodeling has resulted in this protease receiving considerable attention from the pharmaceutical industry. In the last decade, intense research efforts were aimed at development of cathepsin K inhibitors for treatment of osteoporosis and other skeletal disorders associated with pathological bone loss. Emerging new evidence suggests that in addition to bone resorption, cathepsin K is involved in the turnover of extracellular matrix proteins in organs, such as the lung, thyroid and skin, and plays important roles in cardiovascular disease, inflammation and obesity.
This review highlights the physiological and pathophysiological implications of this potent protease, with a focus on recent developments in the design and use of cathepsin K inhibitors to target skeletal pathologies. Therapeutic implications of anticathepsin K drugs in the context of common links between bone disease and atherosclerosis are also discussed.
The association of cathepsin K with skeletal and cardiovascular disorders offers intriguing future applications for inhibitors of this potent protease.
直到最近，组织蛋白酶 K 才被公认为一种骨吸收酶，仅在破骨细胞中选择性表达。其对正常骨重塑的重要性，使该蛋白酶受到制药行业的广泛关注。在过去十年中，研究人员集中精力开发组织蛋白酶 K 抑制剂，以治疗骨质疏松症和其他与病理性骨丢失相关的骨骼疾病。新出现的证据表明，除了骨吸收，组织蛋白酶 K 还参与肺、甲状腺和皮肤等器官的细胞外基质蛋白的周转，并在心血管疾病、炎症和肥胖中发挥重要作用。
本综述强调了这种强效蛋白酶的生理和病理生理学意义，重点介绍了设计和使用组织蛋白酶 K 抑制剂来靶向骨骼疾病的最新进展。还讨论了抗组织蛋白酶 K 药物在骨骼疾病和动脉粥样硬化之间常见联系方面的治疗意义。
组织蛋白酶 K 与骨骼和心血管疾病的关联为这种强效蛋白酶抑制剂提供了有趣的未来应用。
