Design and Evaluation of Novel Small Molecule Activators for AMPK: An In-silico Approach

AMP-activated protein kinase (AMPK) plays an important role in regulating energy homeostasis in eukaryotic cells. AMPK is an attractive therapeutic target for managing metabolic diseases such as type 2 diabetes and cancers[1-3]. Nowadays, In Silico study and evaluations are applied through virtual screening tools, such as molecular docking simulations and predictions of ADMET-related properties to investigate new potent activators for target proteins. The molecular docking simulation is performed to achieve the best binding affinity and docking scores. This is done by comparison between the standard recently reported activator and high-scoring selected ligands. Using data servers’ libraries as PubChem, some similar compounds selected and simulation molecular docking has occurred. Active site was studied and newly selected ligands were applied to molecular docking simulation in active site and other active cavities in target protein. The results were evaluated and high quantities in binding affinities were selected as candidate ligands. Then prediction of ADMET related properties occurred using ADMETLab 2.0 and prediction results were compared with molecular docking results. Finally, 5-[[6-chloro-5-(3-methyl-1H-indol-5-yl)- 1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid and 6-[2-(3-carboxy-4-methylphenoxy)-6- chloro-1H-benzimidazol-5-yl]-3-methylindole-1-carboxylic acid have best results and must be considerate as potent activator for AMP-activated protein kinase