蛋白水解靶向嵌合体（PROTACs）：精准医学中的一种新兴治疗模式。
PROTACs: An Emerging Therapeutic Modality in Precision Medicine.
机构信息
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Department of Chemistry, Yale University, New Haven, CT 06511, USA; Department of Pharmacology, Yale University, New Haven, CT 06511, USA.
出版信息
Cell Chem Biol. 2020 Aug 20;27(8):998-1014. doi: 10.1016/j.chembiol.2020.07.020. Epub 2020 Aug 13.
Targeted protein degradation (TPD) has emerged as an exciting new era in chemical biology and drug discovery. PROteolysis TArgeting Chimera (PROTAC) technology targets cellular proteins for degradation by co-opting the ubiquitin-proteasome system. Over the last 5 years, numerous studies have expanded our understanding of the unique mode of action and advantages of PROTACs, which has in turn spurred interest in both academia and industry to explore PROTACs as a novel therapeutic strategy. In this review, we first highlight the key advantages of PROTACs and then discuss the spatiotemporal regulation of protein degradation. Next, we explore current chemically tractable E3 ligases focusing on expanding the existing repertoire with novel E3 ligases to uncover the full potential of TPD. Collectively, these studies are guiding the development of the PROTAC technology as it emerges as a new modality in precision medicine.
靶向蛋白降解（TPD）技术已经成为化学生物学和药物发现领域的一个令人兴奋的新时代。PROteolysis TArgeting Chimera（PROTAC）技术通过利用泛素-蛋白酶体系统将细胞内的蛋白质靶向降解。在过去的 5 年中，大量的研究扩展了我们对 PROTACs 独特作用模式和优势的理解，这反过来又激发了学术界和工业界的兴趣，将 PROTACs 作为一种新的治疗策略进行探索。在这篇综述中，我们首先强调了 PROTACs 的关键优势，然后讨论了蛋白质降解的时空调控。接下来，我们探讨了当前可化学修饰的 E3 连接酶，重点是通过新型 E3 连接酶来扩展现有库，以充分发挥 TPD 的潜力。总的来说，这些研究正在指导 PROTAC 技术的发展，因为它作为精准医学的一种新模式出现。
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