Small-molecule drug design strategies for regulating protein phosphorylation modification
- VernacularTitle:调控蛋白磷酸化修饰的小分子设计策略
- Author:
Wen-yan YANG
1
,
2
,
3
;
Jia-yi WANG
1
,
2
,
3
;
Feng-jiao LIN
1
,
2
,
3
;
Ke-ran WANG
1
,
2
,
3
;
Yu-zhuo WU
1
,
2
,
3
;
Zhao-cheng WANG
1
,
2
,
3
;
Qi-dong YOU
1
,
2
,
3
;
Lei WANG
1
,
2
,
3
;
Qiu-yue ZHANG
1
,
2
,
3
Author Information
- Publication Type:Research Article
- Keywords: phosphorylation regulation; small molecule design; inase; phosphatase; bifunctional molecule
- From: Acta Pharmaceutica Sinica 2024;59(11):2912-2925
- CountryChina
- Language:Chinese
- Abstract: Protein phosphorylation modification is an important mechanism of physiological regulation that is closely related to protein biological functions. In particular, protein kinases are responsible for catalyzing the phosphorylation process of proteins, and phosphatases are responsible for catalyzing the dephosphorylation process of phosphorylation-modified proteins, which together mediate the achievement of dynamic and reversible phosphorylation modifications of proteins. Abnormal phosphorylation levels of proteins contribute to the development of many diseases, such as cancer, neurodegenerative diseases, and chronic diseases. Therefore, rational design of small molecules to regulate protein phosphorylation is an important approach for disease treatment. Based on the mechanism of protein phosphorylation regulation, small molecule drug design strategies can be classified into three types, protein kinase modulators, phosphatase modulators, and bifunctional molecules with proximity-mediated mechanism. This review emphasizes the above three small molecule design strategies for targeting protein phosphorylation regulation, including molecular design ideas, research progress and current challenges, and provides an outlook on small molecule modulators targeting protein phosphorylation modification.
