In-silico analysis for the confirmation of insulin receptor as a target for reported GLUT4 anti-diabetic natural compounds

Purpose of Research: There are 425 million people with diabetes in the World. There will be 629 million people with diabetes in the World in 2045. The insulin receptor controls glucose homeostasis, a physiological mechanism that can lead to diabetes and cancer if disrupted. Scope of The Experiments: This study aimed to confirm the Insulin Receptor target for reported GLUT4 anti-diabetic natural compounds based on their pharmacokinetic properties, toxicity prediction, molecular docking, target analysis, similar FDA approved drugs prediction, and molecular dynamic simulation. We selected 24 compounds on the basis of their mode of action from the anti-diabetic natural compounds database (ADNCD). Initially, we performed ADME analysis for the selected 24 compounds. Results: Among these 24 compounds, it has been found that 18 compounds followed the Lipinski Rule of Five. Further, we did a toxicity analysis of those 18 compounds, and it was found that 15 compounds were toxic in nature. We performed molecular docking against the Insulin Receptor (PDB ID: 1IR3) of the rest of the 3 compounds after ADME and toxicity analysis. To understand the dynamic motions of the ligand-protein complex, we perform a root mean square fluctuation analysis. We also checked the similarity of Apigenin from the FDA-approved drugs, but no similar molecule was found. Findings and Conclusions: It has been found that Apigenin was selected as the best compound as it showed the lowest binding energy and satisfied all our study parameters. Our promising findings based on preliminary and in-silico analysis need to be validated further by in-vitro and in-vivo studies.