连接器
药物发现
计算生物学
靶蛋白
蛋白质水解
支架蛋白
脚手架
生物
化学
小分子
生物化学
计算机科学
酶
信号转导
数据库
基因
操作系统
作者
Liwen Xia,Meng-Yu Ba,Wei Liu,Weyland Cheng,Chao-Ping Hu,Qingjie Zhao,Yongfang Yao,Moran Sun,Yongtao Duan
出处
期刊:Future Medicinal Chemistry
[Newlands Press Ltd]
日期:2019-11-01
卷期号:11 (22): 2919-2973
被引量:31
标识
DOI:10.4155/fmc-2019-0159
摘要
Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC. Some PROTACs with a triazole linker have displayed promising anticancer activity. This review provides an overview of PROTACs with a triazole scaffold and discusses its structure–activity relationship. Important milestones in the development of PROTACs are addressed and a critical analysis of this drug discovery strategy is also presented.Graphical abstract is adapted with permission from Kymera Therapeutics; Figure 1 in Jarvis LM. Targeted protein degraders are redefining how small molecules look and act. C– 96(8) (2018) https://cen.acs.org/articles/96/i8/targeted-protein-degraders-are-redefining-how-small-molecules-look-and-act.html.
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