蛋白质水解
泛素连接酶
泛素
蛋白质降解
蛋白酶体
计算生物学
跨膜蛋白
药物开发
小分子
靶蛋白
药物发现
化学
细胞生物学
药品
生物
生物化学
药理学
酶
受体
基因
出处
期刊:PubMed
日期:2023-09-25
卷期号:39 (9): 3615-3627
标识
DOI:10.13345/j.cjb.221040
摘要
Proteolysis targeting chimera (PROTAC) refers to heterobifunctional small molecules that can simultaneously bind an E3 ubiquitin ligase and a target protein, enabling specific degradation of the target protein with the aid of the ubiquitin proteasome system. At present, most PROTAC drugs are in the clinical trial stage, and the ligands are mainly non-covalent compounds. PROTAC drugs have the advantage of overcoming drug resistance and degrading "undruggable" target proteins, but non-covalent ligands could lead to the hook effect that undermines drug efficacy. With its own advantages, covalent ligands can avoid the occurrence of this phenomenon, which is of great help to the development of PROTAC. This review summarizes the progress in preclinical and clinical research and application of PROTAC molecules targeting three different classes of protein targets, including intranuclear, transmembrane, and cytosolic proteins. We also offer perspective discussions to provide research ideas and references for the future development of PROTAC.
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