Glucokinase (GK), also known as hexokinase IV or D, is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. While, Glucokinase occurs in cells in the liver, pancreas, gut, and brain of humans and most other vertebrates. In addition, compared with other hexokinases, glucokinase has a lower affinity for glucose. Glucokinase plays a critical role in the control of whole-body glucose homeostasis. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia. Moreover, glucokinase functions as a key ‘glucose sensor’ and plays a central role in glucose homeostasis by maintaining blood glucose levels within a narrow range of 4-6 mM. Thus pharmacological activation of glucokinase may provide a unique mechanism of action to address the underlying cause of type 2 diabetes.
Dorzagliatin (also known as HMS5552) is an orally active and fourth-generation dual-acting glucokinase (GK) activator.
This campound has a structurally novel amino-acid-based chemical scaffold. Dorzagliatin has the potential for type 2 diabetes research. In addition, Dorzagliatin shows significant improvement in β-cell function and glycaemic control. In a recent study, Dorzagliatin has the improvements of glucokinase activity and insulin resistance in a rat model of type 2 diabetes mellitus induced by a high-fat diet and Streptozotocin (STZ). Compared with diabetic rats, Dorzagliatin significantly decreases the fasting plasma insulin (FINS) level. Furthermore, Dorzagliatin exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance.
To sum up, Dorzagliatin is an orally active and fourth-generation dual-acting glucokinase activator, has the potential for type 2 diabetes research.
 Xiao-Xue Zhu, et al. Diabetes Obes Metab. 2018 Sep;20(9):2113-2120.