National Pharmaceutical Teaching Laboratory Center, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Eur J Med Chem. 2022 May 5;235:114290. doi: 10.1016/j.ejmech.2022.114290. Epub 2022 Mar 15.
Protein degradation technology has progressed dramatically since 2001 when proteolysis targeting chimera (PROTAC) was first reported. Various of distinctive degradation technologies based on PROTAC have been developed for the degradation of kinases, nuclear receptors, epigenetic proteins, misfolded proteins, and also RNAs, etc. These technologies greatly broaden the spectrum of targets and the scope of clinical applications for the treatment of cancer, neurodegenerative diseases and virus diseases, etc. More than 15 targeted degraders have been in the clinic to date. Here in this review, we summarized the constituents and examples of different degradation strategies, as well as their advantages and limitations.
自 2001 年首次报道蛋白水解靶向嵌合体（PROTAC）以来，蛋白质降解技术取得了显著进展。基于 PROTAC，已经开发了各种独特的降解技术，可用于降解激酶、核受体、表观遗传蛋白、错误折叠蛋白以及 RNA 等。这些技术极大地拓宽了治疗癌症、神经退行性疾病和病毒疾病等的靶标范围和临床应用范围。迄今为止，已有超过 15 种靶向降解剂进入临床研究。在本文综述中，我们总结了不同降解策略的组成部分和实例，以及它们的优缺点。
