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.

中文翻译：

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靶向蛋白质降解：PROTAC设计的要素。

使用靶向蛋白水解的嵌合体（PROTAC）的靶向蛋白降解已成为药物发现中的新型治疗手段。PROTAC通过劫持E3泛素连接酶的POI泛素化活性并随后被26S蛋白酶体降解，从而介导特定目标蛋白（POI）的降解。这种劫持机制已被用于降解各种类型的疾病相关POI。在这篇综述中，我们旨在突出针对性蛋白质降解的最新进展，并描述为了有效开发有效的PROTACs需要解决的挑战。