Advances in nucleoside analogues as methyltransferase inhibitors
10.16438/j.0513-4870.2023-1406
- VernacularTitle:核苷类甲基转移酶抑制剂的研究进展
- Author:
Jun-jie ZHANG
1
;
Tong-chao LIU
2
;
Bing XIONG
1
Author Information
1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
epigenetics;
italic>S-adenosyl-L-methionine;
methyltransferase;
nucleoside analogue
- From:
Acta Pharmaceutica Sinica
2024;59(5):1126-1150
- CountryChina
- Language:Chinese
-
Abstract:
As the second largest cofactor after ATP in body, S-adenosyl-L-methionine (SAM) is responsible for methyl donor in SAM-dependent methyltransferases (MTases). The methylation of essential ingredients (e.g., DNA, RNA, protein) plays a critical role in epigenetic regulation, cellular signal transduction and metabolic cycles, which is closely related to different kinds of diseases. Therefore, SAM-dependent methyltransferases are considered as promising drug targets. Currently, a growing number of nucleoside analogues have been developed as SAM-competitive inhibitors, blocking the downstream signaling pathways to cure diseases. In the review, we outline the design strategy and optimization process of methyltransferase inhibitors, analyze the shortcomings and solutions of developing nucleoside derivatives as MTase inhibitors, to provide guidance and broad direction to the development of nucleoside MTase inhibitors.
