Advances in the discovery of cathepsin K inhibitors on bone resorption.
Advances in the discovery of cathepsin K inhibitors on bone resorption.
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DOI：
10.1080/14756366.2018.1465417
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发表时间：
2018-12
影响因子：
5.6
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Lu J;Wang M;Wang Z;Fu Z;Lu A;Zhang G
组织蛋白酶 K (Cat K) 在破骨细胞中高表达，是组织蛋白酶溶酶体蛋白酶家族的半胱氨酸蛋白酶成员，由于其在骨基质降解中的作用，作为药物化学研究的目标越来越受到人们的关注。 Cat K 酶的抑制可减少骨吸收，因此使该酶成为抗吸收性骨质疏松症治疗的有吸引力的靶标。在过去的几十年里，人们在设计和开发高效、选择性极佳和口服适用的 Cat K 抑制剂方面付出了巨大的努力。这些抑制剂来源于合成化合物或天然产物，其中一些已经通过了临床前研究，目前正处于不同进展阶段的临床试验中。本文简要总结了Cat K抑制剂的历史发展，并讨论了抑制剂结构与Cat K活性位点之间的关系，以指导未来抑制剂的发展。
Cathepsin K (Cat K), highly expressed in osteoclasts, is a cysteine protease member of the cathepsin lysosomal protease family and has been of increasing interest as a target of medicinal chemistry efforts for its role in bone matrix degradation. Inhibition of the Cat K enzyme reduces bone resorption and thus, has rendered the enzyme as an attractive target for anti-resorptive osteoporosis therapy. Over the past decades, considerable efforts have been made to design and develop highly potent, excellently selective and orally applicable Cat K inhibitors. These inhibitors are derived from synthetic compounds or natural products, some of which have passed preclinical studies and are presently in clinical trials at different stages of advancement. In this review, we briefly summarised the historic development of Cat K inhibitors and discussed the relationship between structures of inhibitors and active sites in Cat K for the purpose of guiding future development of inhibitors.
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