Hepatitis C virus NS3/4a protease inhibitors
Hepatitis C virus NS3/4a protease inhibitors
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DOI：
10.1016/j.coph.2016.07.015
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发表时间：
2016-10-01
影响因子：
4
通讯作者：
Rudd, Michael T.
中科院分区：
文献类型：
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作者：
McCauley, John A.;Rudd, Michael T.
丙型肝炎病毒（HCV）感染是全球性的重大健康问题，HCV NS 3/4a蛋白酶抑制剂是近20年来研究的热点。从第一次鉴定底物衍生肽抑制剂到目前可用的复杂大环化合物，包括帕利匹韦和格拉佐匹韦，该领域已经使用基于结构的设计来面对效力，耐药性和药代动力学的问题。来自众多公司的众多突破性结构已经导致化合物成为现在联合治疗的关键成分，治愈率> 90%。在本文中，我们详细介绍了已经进入临床试验的化合物，包括它们的设计及其对NS 3/4a蛋白酶领域的影响。
Hepatitis C virus (HCV) infection is a major health issue around the world and HCV NS3/4a protease inhibitors have been the focus of intensive research for the past 20 years. From the first identification of substrate-derived peptide inhibitors to the complex, macrocyclic compounds, including paritaprevir and grazoprevir, that are currently available, the field has used structure-based design to confront the issues of potency, resistance and pharmacokinetics. Numerous breakthrough structures from a multitude of companies have led to compounds that are now key components of combination therapies with cure rates of >90%. Herein, we detail the compounds that have advanced to clinical trials including their design and their impact on the NS3/4a protease field.