Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Institute of Materia Medica, Hangzhou Medical College, Hangzhou, 310013, PR China; School of Pharmacy, Hangzhou Medical College, Hangzhou, 310013, PR China.
Center for Molecular Medicine, Hangzhou Medical College, Hangzhou, 310013, PR China.
Eur J Med Chem. 2021 Jan 15;210:112981. doi: 10.1016/j.ejmech.2020.112981. Epub 2020 Oct 31.
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.
蛋白水解靶向嵌合体（PROTAC）通过泛素-蛋白酶体途径，劫持靶蛋白（POI）并招募 E3 连接酶进行目标降解，是一种新的药物发现范式，已被广泛用作具有临床应用价值的生物工具和药物分子。目前，设计用于专门靶向雄激素受体（AR）的口服小分子 PROTAC ARV-110 首先进入转移性去势抵抗性前列腺癌的临床 I 期试验，为 PROTAC 的发展开辟了新途径。本文详细总结了 PROTAC 靶向各种蛋白质的最新一年进展，并阐明了 PROTAC 技术的优势。最后，还讨论了该充满活力的领域的潜在挑战。
