The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
复制标题
DOI：
10.1016/j.bmcl.2007.12.047
复制
发表时间：
2008-02-01
影响因子：
2.7
通讯作者：
Black, W. Cameron
中科院分区：
文献类型：
--
作者：
Gauthier, Jacques Yves;Chauret, Nathalie;Black, W. Cameron
Odanacatib是一种强效、选择性和中性组织蛋白酶K抑制剂，开发用于解决Cat K抑制剂L-873724的代谢问题。取代P1和修饰P2侧链导致在临床前物种中具有长半衰期的代谢稳健的抑制剂。Odanacatib在全细胞试验中的选择性高于已发表的Cat K抑制剂balicatib和relacatib。真皮成纤维细胞培养物中的评价显示，相对于选择性较低的Cat K抑制剂，细胞内胶原蛋白蓄积最少。(C)2008爱思唯尔有限公司保留所有权利。
Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.