On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications.
On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications.
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DOI：
10.1515/bmc.2011.034
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发表时间：
2011-10-01
影响因子：
--
通讯作者：
Day R
中科院分区：
文献类型：
--
作者：
Couture F;D'Anjou F;Day R
越来越多的人对靶向治疗重要疾病的蛋白水解酶感兴趣。此外，新的基于蛋白质的治疗策略有可能扩大针对这些病理的可用治疗方法。在过去的十年里，越来越多的证据证实，被称为原蛋白转换酶(PC)的蛋白酶家族是病毒感染、骨关节炎、癌症和心血管疾病等的潜在靶点。然而，考虑到观察到的一些PC基因敲除小鼠的胚胎致死性，对于靶向PC在治疗背景下的相关性，特别是关于预期的治疗副作用，仍然有许多悬而未决的问题。在这篇综述中，将讨论PC作为药理靶点的益处，重点是概念和策略，以及现有和未来抑制剂的进展状况。
There is increasing interest in the therapeutic targeting of proteases for the treatment of important diseases. Additionally new protein-based therapeutic strategies have the potential to widen the available treatments against these pathologies. In the last decade, accumulated evidence has confirmed that the family of proteases known as proprotein convertases (PCs) are potential targets for viral infections, osteoarthritis, cancer and cardiovascular disease, among others. Nevertheless, there are still many unanswered questions about the relevance of targeting PCs in a therapeutic context, especially regarding the anticipated secondary effects of treatment, considering the observed embryonic lethality of some PC knockout mice. In this review, the benefits of PCs as pharmacological targets will be discussed, with focus on concepts and strategies, as well as on the state of advancement of actual and future inhibitors.