Abstract / Summary
Abstract Receptor for Advanced Glycation End Products refers to RAGE belongs to a superfamily of immunoglobulin (Ig) cell surface receptors that is currently considered to be central to the pathogenesis of diabetes and its complications. Various ligands to the pattern recognition receptor RAGE, which identifies endogenous stress signals, include High Mobility Group Box 1, Advanced Glycation End products, S100 proteins, amyloid-beta, some nucleic acids, phospholipids, and glycosaminoglycans. In this study, we used an in silico virtual screening approach, performing molecular docking with 6,000 bioactive molecules, and the top 5 were selected for ADMET and Molecular Dynamics Simulation (MDS) profiling based on the best docking scores. CID-72426 and CID-71618826 were found to exhibit strong binding affinities that were -7.1 and -6.9 kcal/mol, respectively, which is far better than the control drug Azeliragon (CID-11180124), which showed a binding affinity of −3.1 kcal/mol. Both substances exhibited favorable ADME properties and minimal toxicity and further evaluation was done by performing MDS simulations over 100 ns. These novel findings indicate CID-72426 and CID-71618826 as ideal candidates for inhibiting RAGE protein expression. Furthermore, in vivo and in vitro experiment need be conducted in the following series to confirm our computational identification as a potential therapeutic.