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Background: Deficiency of insulin signaling in type 2 diabetes results from insulin resistance or defective insulin secretion and induce hyperglycemia. Diabetes is a global threat that continues to increase day by day at a very high rate in both developing and developed countries. Glucokinase activators (GKA) can be a novel target used for better management of type 2 diabetes. Recently novel GKA Dorzagliatin received market approval by Japan FDA for treatment of type 2 diabetes. Objective: The purpose of designing glucokinase activators was to develop novel therapeutic molecules with minimum side effects. Methods: A docking study was conducted using AutoDock Vina 1.5.6, and the structures were created using ChemBiodraw Ultra. The Swiss ADME algorithm was used for online log p prediction. Results: Among all the molecules designed, AM35 had the highest binding affinity to GK receptors. For good absorption and elimination, Log P values range from 2-3.08, indicating good lipophilic properties. Conclusion: The new lead molecules were designed as glucokinase activators, which had a better pharmacokinetic profile and higher binding affinity.
Mehra et al. (Tue,) studied this question.