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Abstract：
Proteolysis targeting chimera (PROTAC), hijacking protein of interest (POI) and recruiting E3 ligase for target degradation via the ubiquitin-proteasome pathway, is a novel drug discovery paradigm which has been widely used as biological tools and medicinal molecules with the potential of clinical application value. Currently, ARV-110, an orally small molecule PROTAC was designed to specifically target Androgen receptor (AR), firstly enters clinical phase I trials for the treatment of metastatic castration-resistant prostate cancer, which turns a new avenue for the development of PROTAC. We herein provide a detail summary on the latest one year progress of PROTAC target various proteins and elucidate the advantages of PROTAC technology. Finally, the potential challenges of this vibrant field are also discussed.
摘要：
蛋白水解靶向嵌合体(PROTAC),劫持目标蛋白（POI）并通过泛素-蛋白酶体途径招募E3连接酶进行靶标降解，作为具有潜在临床应用价值的生物工具和药用分子,是一种新型的药物发现范式。目前,ARV-110是一种口服小分子PROTAC，旨在特异性靶向雄激素受体（AR），首先进入治疗转移性去势耐药前列腺癌的临床I期试验，这为PROTAC的发展开辟了一条新途径。我们在此提供对PROTAC靶向各种蛋白质的最新一年进展的详细总结，并阐明PROTAC技术的优势。最后,还讨论了这个充满活力的领域的潜在挑战。
