泛素连接酶
蛋白质降解
蛋白质水解
三元络合物
泛素
计算生物学
细胞生物学
化学
蛋白酶体
生物
生物化学
酶
基因
作者
Zhifeng Hu,Craig M. Crews
出处
期刊:ChemBioChem
[Wiley]
日期:2021-09-23
卷期号:23 (2)
被引量:107
标识
DOI:10.1002/cbic.202100270
摘要
Proteolysis-targeting chimeras (PROTACs), an emerging paradigm-shifting technology, hijacks the ubiquitin-proteasome system for targeted protein degradation. PROTACs induce ternary complexes between an E3 ligase and POI, and this induced proximity leads to polyUb chain formation on substrates and eventual proteasomal-mediated POI degradation. PROTACs have shown great therapeutic potential by degrading many disease-causing proteins, such as the androgen receptor and BRD4. The PROTAC technology has advanced significantly in the last two decades, with the repertoire of PROTAC targets increased tremendously. Herein, we describe recent developments of PROTAC technology, focusing on mechanistic and kinetic studies, pharmacokinetic study, spatiotemporal control of PROTACs, covalent PROTACs, resistance to PROTACs, and new E3 ligands.
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