Triple agonist: difference between revisions
Diff·revision 4 → 5·03:25, 29 Oct 2024
Difference between revision 4 and revision 5 of Triple agonist. 5 lines changed; the page grew by 503 bytes.
| Revision 4 — 21:45, 16 Oct 2024 BetaCellBoyd (talk) split §Pharmacology into receptor binding and downstream signalling 2,043 bytes ±0 | Revision 5 — 03:25, 29 Oct 2024 RedirectRini (talk) add the excipient list from the labelling 2,546 bytes +503 | ||
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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 | Adding glucagon-receptor agonism introduces an effect that opposes the others glycaemically, in exchange for increased energy expenditure and reduced hepatic fat. The balance is the central difficulty. See [[Glucagon]].{{r|jastreboff2023}} | |
| + | 13 | ||
| 12 | == Why three receptors == | 14 | == 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}} | 15 | 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}} |
| ⋮ | ⋮ | ||
| 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}} | 17 | 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 | 18 | ||
| + | 19 | Reported potency ratios are assay-dependent and are not comparable between publications, a caution that applies with more force here because three numbers are being compared rather than two.{{r|coskun2022}} | |
| + | 20 | ||
| 17 | == References == | 21 | == References == |
| 18 | {{reflist}} | 22 | {{reflist}} |
| ⋮ | ⋮ | ||
| 23 | [[Category:Dual and triple agonists]] | 27 | [[Category:Dual and triple agonists]] |
| 24 | [[Category:Receptor pharmacology]] | 28 | [[Category:Receptor pharmacology]] |
| + | 29 | [[Category:Articles describing unapproved compounds]] | |
| 25 | 30 |