STAT3 as novel drug target for multiple age-related disorders: docking and simulation analysis

Signal transducer and activator of transcription 3 (STAT3) considerably contributes to various age-related disorders (ARDs) for instance cancer, autoimmune disorders, bowel-associated disorders, Alzheimer's disease, Parkinson's disease and age-related macular degeneration. Previous studies have substantiated that obstructing STAT3 activity may cure an amount of ARDs. Studies on STAT3 have proved it as a novel and promising drug target. In this study, a docking-based virtual screening combined with molecular dynamics simulation was executed to ascertain STAT3 dimerization inhibitors. It was indicated that ligand 01 (ZINC20601870) and ligand 02 (ZINC01216760) exhibited remarkably higher binding affinities (binding affinity with ligand 01 = -8,01 Kcal/mol, binding affinity with ligand 02 = -6,91 Kcal/mol) compared to other ligands. These two ligands reached equilibrium with STAT3 in molecular dynamics simulation. Hence, in this work, we suggest ligand 01 and 02 as a promising lead for further optimization and may serve as drug molecules in therapeutics of multiple ARDs.