靶向蛋白降解：PROTAC 设计要素。
Targeted protein degradation: elements of PROTAC design.
机构信息
Molecular, Cellular, and Developmental Biology Department, Yale University, 219 Prospect Street, KBT 400, New Haven, CT, 06511, United States.
Molecular, Cellular, and Developmental Biology Department, Yale University, 219 Prospect Street, KBT 400, New Haven, CT, 06511, United States.
出版信息
Curr Opin Chem Biol. 2019 Jun;50:111-119. doi: 10.1016/j.cbpa.2019.02.022. Epub 2019 Apr 17.
Abstract
Targeted protein degradation using Proteolysis Targeting Chimeras (PROTACs) has emerged as a novel therapeutic modality in drug discovery. PROTACs mediate the degradation of select proteins of interest (POIs) by hijacking the activity of E3 ubiquitin ligases for POI ubiquitination and subsequent degradation by the 26S proteasome. This hijacking mechanism has been used to degrade various types of disease-relevant POIs. In this review, we aim to highlight the recent advances in targeted protein degradation and describe the challenges that need to be addressed in order to efficiently develop potent PROTACs.
摘要
利用蛋白水解靶向嵌合体（PROTACs）进行靶向蛋白降解已成为药物发现中的一种新的治疗模式。PROTACs 通过劫持 E3 泛素连接酶对靶蛋白（POI）的泛素化和随后的 26S 蛋白酶体降解，介导对特定感兴趣的蛋白质（POI）的降解。这种劫持机制已被用于降解各种类型的与疾病相关的 POI。在这篇综述中，我们旨在强调靶向蛋白降解的最新进展，并描述为了有效地开发有效的 PROTACs 而需要解决的挑战。
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