Triple agonist: difference between revisions
Diff·revision 1 → 2·14:08, 26 Sep 2024
Difference between revision 1 and revision 2 of Triple agonist. 6 lines changed; the page grew by 872 bytes.
| Revision 1 — 07:20, 23 Sep 2024 MazdutideMads (talk) start article on the compound 1,171 bytes +1,171 | Revision 2 — 14:08, 26 Sep 2024 ReceptorRhoda (talk) move a stray full stop inside the reference 2,043 bytes +872 | ||
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| 10 | The design extends the logic of the [[Dual incretin agonist|dual agonists]] by one receptor, and multiplies the constraints accordingly: the sequence must retain activity at three targets in a ratio fixed by chemistry, and that ratio must remain appropriate across the whole dose range.{{r|coskun2022}} | 10 | The design extends the logic of the [[Dual incretin agonist|dual agonists]] by one receptor, and multiplies the constraints accordingly: the sequence must retain activity at three targets in a ratio fixed by chemistry, and that ratio must remain appropriate across the whole dose range.{{r|coskun2022}} |
| 11 | 11 | ||
| + | 12 | == Why three receptors == | |
| + | 13 | Each added receptor is intended to contribute a mechanism the others do not. GLP-1 agonism supplies appetite suppression and glucose-dependent insulin secretion; GIP agonism appears to improve tolerability and contributes adipose-tissue effects; glucagon agonism raises energy expenditure and mobilises hepatic fat.{{r|coskun2022}} | |
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| + | 15 | Because the receptors share a common architecture and their ligands a common precursor family, a peptide can be engineered to engage all three — see [[Proglucagon]] — but the sequence space in which all three activities coexist at usable ratios is narrow.{{r|jastreboff2023}} | |
| + | 16 | ||
| 12 | == References == | 17 | == References == |
| 13 | {{reflist}} | 18 | {{reflist}} |
| 14 | <ref name="coskun2022">Coskun T, Urva S, Roell WC, et al. "LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist." ''Cell Metabolism'' 34(9):1234–1247 (2022). PMID 35985340.</ref> | 19 | <ref name="coskun2022">Coskun T, Urva S, Roell WC, et al. "LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist." ''Cell Metabolism'' 34(9):1234–1247 (2022). PMID 35985340.</ref> |
| + | 20 | <ref name="jastreboff2023">Jastreboff AM, Kaplan LM, Frías JP, et al. "Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial." ''New England Journal of Medicine'' 389(6):514–526 (2023). PMID 37366315.</ref> | |
| 15 | 21 | ||
| 16 | {{DEFAULTSORT:Triple agonist}} | 22 | {{DEFAULTSORT:Triple agonist}} |