Amylin receptor agonist: difference between revisions
Diff·revision 3 → 4·13:00, 25 Oct 2024
Difference between revision 3 and revision 4 of Amylin receptor agonist. 5 lines changed; the page grew by 627 bytes.
| Revision 3 — 17:27, 17 Oct 2024 PrimarySrcPatia (talk) convert the substitution list to a table so the analogues line up 1,601 bytes ±0 | Revision 4 — 13:00, 25 Oct 2024 RedirectRini (talk) expand §Analytical notes 2,228 bytes +627 | ||
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| 10 | Two generations exist. Pramlintide, approved in 2005 as an adjunct to insulin, substitutes three prolines into the human sequence to disrupt β-sheet formation; its short half-life requires injection at each meal, which limited uptake. [[Cagrilintide|Cagrilintide]] is a long-acting analogue employing [[Albumin binding half-life extension|acylation]] for weekly dosing and is under development principally in combination with [[Semaglutide|semaglutide]] as [[CagriSema|CagriSema]].{{r|lau2021}} | 10 | Two generations exist. Pramlintide, approved in 2005 as an adjunct to insulin, substitutes three prolines into the human sequence to disrupt β-sheet formation; its short half-life requires injection at each meal, which limited uptake. [[Cagrilintide|Cagrilintide]] is a long-acting analogue employing [[Albumin binding half-life extension|acylation]] for weekly dosing and is under development principally in combination with [[Semaglutide|semaglutide]] as [[CagriSema|CagriSema]].{{r|lau2021}} |
| 11 | 11 | ||
| + | 12 | == Design == | |
| + | 13 | The problem to be solved is amyloidogenicity. Human amylin forms cross-β fibrils at concentrations well below those needed for a pharmaceutical formulation, and a peptide that aggregates in the vial is not a medicine.{{r|hay2015}} | |
| + | 14 | ||
| + | 15 | Pramlintide takes the rodent solution: rat amylin does not aggregate because prolines at three positions in the central region prevent β-sheet stacking, and pramlintide introduces those substitutions into the human sequence. The result is soluble and stable but retains a short half-life of about 48 minutes, and its acidic formulation cannot be mixed in a syringe with insulin. | |
| + | 16 | ||
| 12 | == References == | 17 | == References == |
| 13 | {{reflist}} | 18 | {{reflist}} |