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Abstract：
Proteolysis targeting chimeras (PROTACs) have been developed to be an effective technology for targeted protein degradation. Each PROTAC contains three key components: a protein-of-interest (POI) ligand, an E3 ligase ligand, and a linker. These bifunctional molecules can hijack the intracellular inherent ubiquitin-proteasome system to degrade different POIs. With several advantages over other therapeutic strategies, PROTACs have set off a new upsurge of drug discovery in recent years. PRTOACs have been extensively explored worldwide and have excelled not only in cancer diseases but also in cardiovascular diseases, fatty liver disease, immune diseases, neurodegenerative diseases, and viral infections. In this review, we aim to summarize the rapid progress from 2010 to 2021 in PROTACs targeting various non-oncoproteins and elucidate the advantages of PROTACs technology. Finally, the potential challenges of this dynamic field are also discussed.
摘要：
蛋白水解靶向嵌合体（PROTACs）已被开发为靶向蛋白质降解的有效技术。每个PROTAC包含三个关键组件：感兴趣的蛋白质（POI）配体，E3连接酶配体，和一个链接。这些双功能分子可以劫持细胞内固有的泛素-蛋白酶体系统以降解不同的POI。与其他治疗策略相比有几个优点，近年来，PROTACs掀起了新的药物发现热潮。PRTOAC在全球范围内得到了广泛的探索，不仅在癌症疾病中而且在心血管疾病中都表现出色。脂肪肝,免疫性疾病，神经退行性疾病，和病毒感染。在这次审查中,我们旨在总结从2010年到2021年针对各种非癌蛋白的PROTACs的快速进展，并阐明PROTACs技术的优势。最后,还讨论了这一动态领域的潜在挑战。
