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新型自噬降解剂在加速药物研究中的应用。

Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

J Med Chem. 2023 Feb 9;66(3):1700-1711. doi: 10.1021/acs.jmedchem.2c01712. Epub 2023 Jan 30.

Abstract

Targeted protein degradation (TPD) technology is based on a unique pharmacological mechanism that has profoundly revolutionized medicinal research by overcoming limitations associated with traditional small-molecule drugs. Autophagy, a mechanism for intracellular waste disposal and recovery, is an important biological process in medicinal research. Recently, studies have demonstrated that several emerging autophagic degraders can treat human diseases. Herein we summarize the progress in medicinal research on autophagic degraders, including autophagosome-tethering compounds (ATTEC), autophagy-targeting chimeras (AUTAC), and AUTOphagy-TArgeting chimeras (AUTOTAC), for treating human diseases. These autophagic degraders exhibit excellent potential for treating neurodegenerative diseases. Our research on autophagic degraders provides a new avenue for medicinal research on TPD via autophagy.

摘要

靶向蛋白降解(TPD)技术基于一种独特的药理学机制,通过克服与传统小分子药物相关的局限性,彻底改变了医学研究。自噬是一种用于细胞内废物处理和回收的机制,是医学研究中的一个重要生物学过程。最近的研究表明,几种新兴的自噬降解剂可用于治疗人类疾病。本文总结了自噬降解剂在治疗人类疾病方面的医学研究进展,包括自噬体连接化合物(ATTEC)、自噬靶向嵌合体(AUTAC)和自噬靶向嵌合体(AUTOTAC)。这些自噬降解剂在治疗神经退行性疾病方面表现出巨大的潜力。我们对自噬降解剂的研究为通过自噬进行 TPD 的医学研究提供了新的途径。

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