Abstract：
Proteolysis-targeting chimeras (PROTACs), bifunctional molecules consisting of a ligand of protein of interest (POI), an E3 ligase ligand and a linker, have been developed to hijack the ubiquitin-proteasome system (UPS) to induce different POIs degradation. Currently, the first oral PROTACs (ARV-110 and ARV-471) have shown encouraging efficacy in clinical trials of prostate and breast cancer treatment, which turns a new avenue for the development of PROTAC research. In this review, we focus on a detailed summary of the latest progress of PROTACs and elucidate the advantages of PROTACs technology. In addition, potential challenges and perspectives of PRTOACs are discussed.
摘要：
蛋白水解靶向嵌合体（PROTACs），由感兴趣的蛋白质（POI）的配体组成的双功能分子，E3连接酶配体和接头，已开发用于劫持泛素-蛋白酶体系统（UPS）以诱导不同的POIs降解。目前,第一个口服PROTACs（ARV-110和ARV-471）在前列腺癌和乳腺癌治疗的临床试验中显示出令人鼓舞的疗效，这为PROTAC研究的发展开辟了一条新途径。在这次审查中,重点对PROTACs的最新进展进行了详细的总结,阐明了PROTACs技术的优势。此外,讨论了PRTOAC的潜在挑战和前景。
