Advances in the allostery of angiotensin II type 1 receptor.
Xi ZhangSuli ZhangMeili WangHao ChenHuirong LiuPublished in: Cell & bioscience (2023)
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.
Keyphrases
- small molecule
- angiotensin ii
- clinical trial
- vascular smooth muscle cells
- angiotensin converting enzyme
- cardiovascular disease
- randomized controlled trial
- type diabetes
- emergency department
- working memory
- metabolic syndrome
- open label
- molecular dynamics
- electronic health record
- drug induced
- drug delivery
- cancer therapy
- current status
- binding protein
- phase ii