Repurposing antihyperlipidemic drugs beyond lipid lowering: In silico approach into its GLP-1 receptor modulator potential
Journal of Research in Pharmacy, cilt.30, sa.2, ss.381-387, 2026 (ESCI, Scopus, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 30 Sayı: 2
- Basım Tarihi: 2026
- Doi Numarası: 10.12991/jrespharm.1822102
- Dergi Adı: Journal of Research in Pharmacy
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, TR DİZİN (ULAKBİM)
- Sayfa Sayıları: ss.381-387
- Anahtar Kelimeler: Drug repurposing, ezetimibe, antihyperlipidemic, GLP-1 receptor, docking
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Drug repositioning has recently become a crucial tool for discovering new biological effects of clinically used drugs. This study investigated the GLP-1 receptor modulator 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 molecular 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 highly comparable those of Danuglipron. Following this analysis, the physicochemical and toxicological properties of Ezetimibe, the most potent compound, and Danuglipron were compared computationally. Docking analyses suggest that while Danuglipron engages the GLP-1 receptor through a canonical orthosteric binding mode, Ezetimibe preferentially occupies a more superficial cavity consistent with a potential allosteric modulatory interaction. This distinction highlights mechanistic differences between peptide-mimetic agonists and repurposed small-molecule candidates.