A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS

Selma Sezen; Feyza Burul

doi:10.62425/rtpharma.1828403

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 kcal/mol). According to ADMET analysis, empagliflozin can cross the blood–brain barrier, has a low risk of hepatotoxicity, and shows potential interactions with androgen receptor and aromatase. Conclusion: In this study, conducted to repurpose empagliflozin via ALS-related mechanisms, which has been reported to have cardioprotective, hepatoprotective, and renoprotective effects in clinical studies, the findings obtained using computational models suggest that empagliflozin may have neuroprotective effects in ALS.

Keywords

Supporting Institution

The authors declared that this study has received no financial support.

Ethical Statement

This study does not require ethics committee approval.

References

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Details

Primary Language

English

Subjects

Clinical Pharmacology and Therapeutics

Journal Section

Research Article

Authors

Selma Sezen
0000-0001-6575-6149
Türkiye

Feyza Burul ^*
0009-0002-2193-1106
Türkiye

Publication Date

January 15, 2026

Submission Date

November 22, 2025

Acceptance Date

December 23, 2025

Published in Issue

Year 2025 Volume: 3 Number: 3

DOI

https://doi.org/10.62425/rtpharma.1828403

IZ

https://izlik.org/JA98YL73ST

Cite

RIS / Bibtex

APA

Sezen, S., & Burul, F. (2026). A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS. Recent Trends in Pharmacology, 3(3), 87-97. https://doi.org/10.62425/rtpharma.1828403

AMA

1.Sezen S, Burul F. A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS. Recent Trends in Pharmacology. 2026;3(3):87-97. doi:10.62425/rtpharma.1828403

Chicago

Sezen, Selma, and Feyza Burul. 2026. “A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS”. Recent Trends in Pharmacology 3 (3): 87-97. https://doi.org/10.62425/rtpharma.1828403.

EndNote

Sezen S, Burul F (January 1, 2026) A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS. Recent Trends in Pharmacology 3 3 87–97.

IEEE

[1]S. Sezen and F. Burul, “A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS”, Recent Trends in Pharmacology, vol. 3, no. 3, pp. 87–97, Jan. 2026, doi: 10.62425/rtpharma.1828403.

ISNAD

Sezen, Selma - Burul, Feyza. “A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS”. Recent Trends in Pharmacology 3/3 (January 1, 2026): 87-97. https://doi.org/10.62425/rtpharma.1828403.

JAMA

1.Sezen S, Burul F. A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS. Recent Trends in Pharmacology. 2026;3:87–97.

MLA

Sezen, Selma, and Feyza Burul. “A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS”. Recent Trends in Pharmacology, vol. 3, no. 3, Jan. 2026, pp. 87-97, doi:10.62425/rtpharma.1828403.

Vancouver

1.Selma Sezen, Feyza Burul. A Drug Repositioning Approach: Antidiabetic Empagliflozin May Be a Potential Drug for the Treatment of ALS. Recent Trends in Pharmacology. 2026 Jan. 1;3(3):87-9. doi:10.62425/rtpharma.1828403