A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS
Abstract
Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which multiple mechanisms play a role in its pathogenesis. However, no radical treatment is currently available for the disease. The potential for repositioning of the antidiabetic drug empagliflozin, which has been reported to have neuroprotective effects in recent studies, in ALS was investigated using computational models. Methods: In this study, to identify ALS-related target proteins, protein–protein interaction networks and disease–gene enrichment analysis were constructed using the STRING database. For molecular docking analyses, the 3D structures of these ALS-associated receptors SOD1 (2C9V), hnRNP A1 (1HA1), TDP-43 (4BS2), SQSTM1/p62 (5YP7) were obtained from the RCSB Protein Data Bank. Empagliflozin and the receptors were prepared using UCSF Chimera v1.19 and AutoDockTools 1.5.7, and binding scores were recorded with AutoDock Vina. The ADMET properties of empagliflozin were determined using ADMETlab 2.0 and LogBB_Pred. Results: In the protein networks generated by STRING, ALS-related proteins with high confidence scores and physical interactions were identified, and among them, four target proteins showing significant interactions and with available PDB codes were selected. Molecular docking analyses revealed that empagliflozin exhibited moderate-to-high binding interactions with SOD1 (-8.5 kcal/mol), TDP-43 (-7.7 kcal/mol), hnRNP A1 (-7.3 kcal/mol), and SQSTM1/p62 (-7.1…
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