Orforglipron (revision 2)
Old revision·10:24, 22 Nov 2024·SemaglutideSasha
This is an old revision of this page, as it stood at 10:24, 22 Nov 2024, saved by SemaglutideSasha with the summary British spelling per PP:MOS. It may differ substantially from the current revision, and any error it contains may since have been corrected.
| Orforglipron | |
|---|---|
| Development code | LY3502970 |
| Class | Small-molecule GLP-1 receptor agonist |
| Route | Oral, once daily |
| Status | Phase 3; not approved |
| Compound infobox · conventions | |
Orforglipron (development code LY3502970) is an investigational orally administered non-peptide agonist of the GLP-1 receptor. It is not a peptide and is not subject to proteolysis, so it requires neither an absorption enhancer nor the strict fasting conditions that govern oral semaglutide.[1]
Small-molecule agonism at a class B G-protein-coupled receptor was long considered difficult, because the natural ligand engages a large surface across two receptor domains.[2] Orforglipron binds a pocket near the extracellular face of the transmembrane bundle and stabilises an active conformation without reproducing the peptide's binding mode.[1]
References
- ^ a b Kawai T, Sun B, Yoshino H, et al. "Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist." Proceedings of the National Academy of Sciences 117(47):29959–29967 (2020). DOI:10.1073/pnas.2014879117. PMID 33177239.
- ^ de Graaf C, Donnelly D, Wootten D, et al. "Glucagon-like peptide-1 and its class B G protein-coupled receptors." Pharmacological Reviews 68(4):954–1013 (2016). PMID 27630114.