Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential

Kerem Buran; Şaban Kalay

doi:10.12991/jrespharm.1822102

Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential

Abstract

Drug repositioning has recently become a crucial tool for discovering new biological effects of clinically used drugs. This study investigated the GLP-1 receptor agonist activity of antihyperlipidemic drugs, which are widely used by diabetic patients and those with cardiovascular diseases.The study was conducted using CB-Dock, an internet-based m olecular docking program. The binding energies (kcal/mol) of the selected antihyperlipidemic drugs to the GLP-1 receptor were calculated, and Danuglipron was used as a reference compound. A comparison of the binding energies revealed that both the binding energy and localization of Ezetimibe were quite like those of Danuglipron. Following this analysis, the physicochemical and toxicological properties of Ezetimibe, the most potent compound, and Danuglipron were compared computationally.

Keywords

Ethical Statement

This study does not involve human participants, animals, or any live cell lines. Therefore, ethical approval was not required.

References

[1] Z. Zheng, Y. Zong, Y. Ma, Y. Tian, Y. Pang, C. Zhang, J. Gao, Glucagon-like peptide-1 receptor: mechanisms and advances in therapy, Signal Transduct Target Ther 9 (2024). https://doi.org/10.1038/s41392-024-01931-z.
[2] S.S. Ibrahim, R.S. Ibrahim, B. Arabi, A. Brockmueller, M. Shakibaei, D. Büsselberg, The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer, Cancer and Metastasis Reviews 43 (2024) 1297–1314. https://doi.org/10.1007/s10555-024-10192-9.
[3] P.E. MacDonald, W. El-kholy, M.J. Riedel, A.M.F. Salapatek, P.E. Light, M.B. Wheeler, The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion, Diabetes 51 (2002). https://doi.org/10.2337/diabetes.51.2007.s434.
[4] T. Bu, Z. Sun, Y. Pan, X. Deng, G. Yuan, Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism, Diabetes Metab J 48 (2024) 354–372. https://doi.org/10.4093/dmj.2023.0277.
[5] J. Chen, A. Mei, Y. Wei, C. Li, H. Qian, X. Min, H. Yang, L. Dong, X. Rao, J. Zhong, GLP-1 receptor agonist as a modulator of innate immunity, Front Immunol 13 (2022) 1–9. https://doi.org/10.3389/fimmu.2022.997578.
[6] C.R. Andreasen, A. Andersen, F.K. Knop, T. Vilsbøll, How glucagon-like peptide 1 receptor agonists work, Endocr Connect 10 (2021) R200–R212. https://doi.org/10.1530/EC-21-0130.
[7] K. Heinla, E. Vasar, I. Reppo, T. Sedman, V. Volke, GLP-1 Receptor Agonists Induce Growth Hormone Secretion in Healthy Volunteers, Diabetes Therapy 14 (2023) 777–786. https://doi.org/10.1007/s13300-023-01381-w.
[8] D.A. Griffith, D.J. Edmonds, J.P. Fortin, A.S. Kalgutkar, J.B. Kuzmiski, P.M. Loria, A.R. Saxena, S.W. Bagley, C. Buckeridge, J.M. Curto, D.R. Derksen, J.M. Dias, M.C. Griffor, S. Han, V.M. Jackson, M.S. Landis, D. Lettiere, C. Limberakis, Y. Liu, A.M. Mathiowetz, J.C. Patel, D.W. Piotrowski, D.A. Price, R.B. Ruggeri, D.A. Tess, A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor, J Med Chem 65 (2022) 8208–8226. https://doi.org/10.1021/acs.jmedchem.1c01856 .

[9] A.R. Saxena, J.P. Frias, L.S. Brown, D.N. Gorman, S. Vasas, N. Tsamandouras, M.J. Birnbaum, Efficacy and Safety of Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron for Glycemic Control Among Patients With Type 2 Diabetes: A Randomized Clinical Trial., JAMA Netw Open 6 (2023) e2314493. https://doi.org/10.1001/jamanetworkopen.2023.14493.
[10] S. Pushpakom, F. Iorio, P.A. Eyers, K.J. Escott, S. Hopper, A. Wells, A. Doig, T. Guilliams, J. Latimer, C. McNamee, A. Norris, P. Sanseau, D. Cavalla, M. Pirmohamed, Drug repurposing: Progress, challenges and recommendations, Nat Rev Drug Discov 18 (2018) 41–58. https://doi.org/10.1038/nrd.2018.168.
[11] L. Sleire, H.E. Førde, I.A. Netland, L. Leiss, B.S. Skeie, P.Ø. Enger, Drug repurposing in cancer, Pharmacol Res 124 (2017) 74–91. https://doi.org/https://doi.org/10.1016/j.phrs.2017.07.013.
[12] Z. Tanoli, A. Fernández-Torras, U.O. Özcan, A. Kushnir, K.M. Nader, Y. Gadiya, L. Fiorenza, A. Ianevski, M. Vähä-Koskela, M. Miihkinen, U. Seemab, H. Leinonen, B. Seashore-Ludlow, M. Tampere, A. Kalman, F. Ballante, E. Benfenati, G. Saunders, S. Potdar, I. Gómez García, R. García-Serna, C. Talarico, A.R. Beccari, W. Schaal, A. Polo, S. Costantini, E. Cabri, M. Jacobs, J. Saarela, A. Budillon, O. Spjuth, P. Östling, H. Xhaard, J. Quintana, J. Mestres, P. Gribbon, A.E. Ussi, D.C. Lo, M. de Kort, K. Wennerberg, M. Fratelli, J. Carreras-Puigvert, T. Aittokallio, Computational drug repurposing: approaches, evaluation of in silico resources and case studies, Nat Rev Drug Discov 24 (2025) 521–542. https://doi.org/10.1038/s41573-025-01164-x.
[13] Y. Liu, M. Grimm, W. tao Dai, M. chun Hou, Z.X. Xiao, Y. Cao, CB-Dock: a web server for cavity detection-guided protein–ligand blind docking, Acta Pharmacol Sin 41 (2020) 138–144. https://doi.org/10.1038/s41401-019-0228-6.
[14] G. Xiong, Z. Wu, J. Yi, L. Fu, Z. Yang, C. Hsieh, M. Yin, X. Zeng, C. Wu, A. Lu, X. Chen, T. Hou, D. Cao, ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties, Nucleic Acids Res 49 (2021) W5–W14. https://doi.org/10.1093/nar/gkab255

Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Kerem Buran ^*
0000-0002-7783-7533
Türkiye

Şaban Kalay
0000-0002-9363-0073
Türkiye

Publication Date

March 15, 2026

Submission Date

November 12, 2025

Acceptance Date

February 4, 2026

Published in Issue

Year 2026 Volume: 30 Number: 2

DOI

https://doi.org/10.12991/jrespharm.1822102

IZ

https://izlik.org/JA39RZ94BR

Cite

RIS / Bibtex

APA

Buran, K., & Kalay, Ş. (2026). Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential. Journal of Research in Pharmacy, 30(2), 381-387. https://doi.org/10.12991/jrespharm.1822102

AMA

1.Buran K, Kalay Ş. Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential. J. Res. Pharm. 2026;30(2):381-387. doi:10.12991/jrespharm.1822102

Chicago

Buran, Kerem, and Şaban Kalay. 2026. “Repurposing Antihyperlipidemic Drugs Beyond Lipid Lowering: In Silico Approach into Its GLP-1 Receptor Agonist Potential”. Journal of Research in Pharmacy 30 (2): 381-87. https://doi.org/10.12991/jrespharm.1822102.

EndNote

Buran K, Kalay Ş (March 1, 2026) Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential. Journal of Research in Pharmacy 30 2 381–387.

IEEE

[1]K. Buran and Ş. Kalay, “Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential”, J. Res. Pharm., vol. 30, no. 2, pp. 381–387, Mar. 2026, doi: 10.12991/jrespharm.1822102.

ISNAD

Buran, Kerem - Kalay, Şaban. “Repurposing Antihyperlipidemic Drugs Beyond Lipid Lowering: In Silico Approach into Its GLP-1 Receptor Agonist Potential”. Journal of Research in Pharmacy 30/2 (March 1, 2026): 381-387. https://doi.org/10.12991/jrespharm.1822102.

JAMA

1.Buran K, Kalay Ş. Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential. J. Res. Pharm. 2026;30:381–387.

MLA

Buran, Kerem, and Şaban Kalay. “Repurposing Antihyperlipidemic Drugs Beyond Lipid Lowering: In Silico Approach into Its GLP-1 Receptor Agonist Potential”. Journal of Research in Pharmacy, vol. 30, no. 2, Mar. 2026, pp. 381-7, doi:10.12991/jrespharm.1822102.

Vancouver

1.Kerem Buran, Şaban Kalay. Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor agonist potential. J. Res. Pharm. 2026 Mar. 1;30(2):381-7. doi:10.12991/jrespharm.1822102