Advances in the allostery of angiotensin II type 1 receptor

Cell & Bioscience

Review

Xi Zhang¹  Meili Wang¹  Hao Chen¹  Suli Zhang¹  Huirong Liu² 

[1] Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 100069, Beijing, People’s Republic of China;Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, Capital Medical University, 100069, Beijing, People’s Republic of China;Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 100069, Beijing, People’s Republic of China;Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, Capital Medical University, 100069, Beijing, People’s Republic of China;Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 10 Xitoutiao, You An Men Street, 100069, Beijing, China;

关键词: Angiotensin II type 1 receptor;    Conformation;    Allostery;    Biased ligands;    Dimers;    Allosteric pocket;   

DOI  :  10.1186/s13578-023-01063-x

 received in 2022-12-30, accepted in 2023-05-31,  发布年份 2023

来源: Springer

【 摘 要 】

Angiotensin II type 1 receptor (AT1R) is a promising therapeutic target for cardiovascular diseases. Compared with orthosteric ligands, allosteric modulators attract considerable attention for drug development due to their unique advantages of high selectivity and safety. However, no allosteric modulators of AT1R have been applied in clinical trials up to now. Except for the classical allosteric modulators of AT1R such as antibody, peptides and amino acids, cholesterol and biased allosteric modulators, there are non-classical allosteric modes including the ligand-independent allosteric mode, and allosteric mode of biased agonists and dimers. In addition, finding the allosteric pockets based on AT1R conformational change and interaction interface of dimers are the future of drug design. In this review, we summarize the different allosteric mode of AT1R, with a view to contribute to the development and utilization of drugs targeting AT1R allostery.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 2