Hormonal
Non-peptide small molecule agonists targeting the GLP-1 receptor orthosteric site can achieve binding affinities and stability comparable to or exceeding existing peptide-based GLP-1RAs, suggesting a viable mechanism for oral administration.
This paper does not offer a current treatment but identifies potential oral drug candidates. It suggests that future oral GLP-1 medications may exist that are as effective as current injectables, addressing the common desire to avoid injections.
Among the studied compounds—especially hits 1, 5, and 9—possessed strong and stable interactions with critical amino acid residues such as TRP-203, PHE-381, and GLN-221 at the active site of the 6X1A-substrate along with favorable pharmacokinetic profiles... Specifically, hit 9 possessed the best docking score with a ∆G_bind value of −102.78 kcal/mol, surpassing even the control compound in binding affinity.
Why this rating
The study is purely in silico (virtual screening and molecular dynamics); no wet-lab or clinical data is presented.
Source
Structure-Based Discovery of Orthosteric Non-Peptide GLP-1R Agonists via Integrated Virtual Screening and Molecular Dynamics
Mansour S. Alturki et al. · International Journal of Molecular Sciences · 2025
DOI 10.3390/ijms26136131
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