Glucokinase as an emerging anti-diabetes target and recent progress in the development of its agonists

被引：49

作者：

Ren, Yixin ^{[1
]}

Li, Li ^{[1
]}

Wan, Li ^{[1
]}

Huang, Yan ^{[1
]}

Cao, Shuang ^{[1
]}

机构：

[1] Wuhan Inst Technol, Sch Chem Engn & Pharm, Key Lab Green Chem Engn Proc, Minist Educ, Wuhan 430205, Peoples R China

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2022年 / 37卷 / 01期

关键词：

Type; 2; diabetes; glucokinase; glucokinase agonist; research progress; drug target; REGULATORY PROTEIN; POSTPRANDIAL GLUCOSE; CRYSTAL-STRUCTURE; TRANSGENIC MICE; ACTIVATOR; GENE; LIVER; MELLITUS; HYPOGLYCEMIA; PF-04937319;

D O I：

10.1080/14756366.2021.2025362

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Type 2 diabetes mellitus is a metabolic disorder with complicated pathogenesis, and mono-target therapy often fails to effectively manage the levels of blood glucose. In recent years, the anti-diabetes target glucokinase (GK) has attracted the attention of researchers. It acts as a glucose sensor, triggering counter regulatory responses following a change in glucose levels to aid restoration of normoglycemia. Activation of GK induces glucose metabolism and reduces glucose levels for the treatment of type 2 diabetes. GK agonists (GKA) are a new class of antidiabetic drugs. Among these agents, dorzagliatin is currently being investigated in phase III clinical trials, while PB-201 and AZD-1656 have reached phase II clinical trials. This article describes the mechanism of action of GK in diabetes and of action of GKA at the protein level, and provides a review of the research, trends, and prospects regarding the use of GKA in this setting.

引用

页码：606 / 615

页数：10

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