Compound monograph
Pramlintide
Pramlintide is an engineered analog of human amylin carrying three proline substitutions, designed to address the aggregation behaviour of the native human sequence.
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Identity & nomenclature
Pramlintide is an engineered analog of human amylin carrying three proline substitutions, designed to address the aggregation behaviour of the native human sequence.
Pramlintide is not another name for human amylin and not identical to rat amylin. It differs from human amylin at exactly three positions: A25P, S28P, S29P. The CAS recorded here is the peptide; a pramlintide acetate record describes a salt and must not replace this identity.
Declared aliases and development codes: AC137.
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Molecular properties
| Molecular formula | C171H267N51O53S2 |
|---|---|
| Molecular mass | 3949.4 Da |
| CAS Registry Number | 151126-32-8 |
| PubChem CID | 70691388 |
| UNII | D3FM8FA78T |
| One-letter sequence | KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY |
Thirty-seven residues, Cys2-Cys7 disulfide, C-terminal Tyr37 amide — identical to human amylin except at three positions, where alanine 25 and serines 28 and 29 are each replaced by proline. It is not lipidated.
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Structural characteristics
Why this molecule exists belongs at the front of any description of it: human amylin aggregates, and the three prolines were introduced to reduce that propensity. The substitutions place it structurally between human amylin and cagrilintide — cagrilintide retains all three prolines and adds N14E, V17R, a Pro37 amide and N-terminal lipidation. The corpus records that chain as a structural relationship only; it is not a claim that the three molecules have interchangeable receptor profiles or physical behaviour. The receptor-comparison study PMID 33727283 tests pramlintide itself alongside selective and nonselective calcitonin-family receptor agonists. Its native amylin comparator is rat amylin, whose sequence differs from human amylin; those comparator data are not evidence for the human-amylin sequence.
- Cys2-Cys7 disulfide
- A25P
- S28P
- S29P
Terminal features: C-terminal amide at Tyr37.
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Molecular targets & mechanisms
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Analytical considerations
THE AGGREGATION CLAIM NEEDS CARE, and this is the entry where the library should be most explicit. Pramlintide is widely described as non-aggregating. Exact-compound work reports it assembling into multimers and forming amyloid fibrils in vitro in a pH-dependent process, characterised by thioflavin T binding, loss of soluble peptide, transmission electron microscopy, atomic force microscopy and X-ray diffraction. Separate biophysical work reports stability at pH 4 across roughly 1.8 to 8.8 mg per mL and a tendency to aggregate at pH 6 to 7.5. Reduced propensity relative to human amylin is real; categorical immunity is not established. Neither the three prolines nor a chromatographic purity figure establishes the absence of higher-order assemblies in a given sample. Identity confirmation should also target positions 25, 28 and 29 specifically rather than relying on regions shared with human amylin.
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Verified bibliography
- A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams.current
Nonoyama A, Laurence JS, Garriques L, Qi H, Le T, Middaugh CR
Journal of pharmaceutical sciences · 2008-07 · Journal Article
- Amyloidogenesis of the amylin analogue pramlintide.current
da Silva DC, Fontes GN, Erthal LC, Lima LM
Biophysical chemistry · 2016-09-20 · Journal Article
- Effects of sequential proline substitutions on amyloid formation by human amylin20-29.current
Moriarty DF, Raleigh DP
Biochemistry · 1999-02-09 · Journal Article
- Development of Cagrilintide, a Long-Acting Amylin Analogue.current
Kruse T, Hansen JL, Dahl K, Schäffer L, Sensfuss U, Poulsen C, Schlein M, Hansen AMK, Jeppesen CB, Dornonville de la Cour C, Clausen TR, Johansson E, Fulle S, Skyggebjerg RB, Raun K
Journal of medicinal chemistry · 2021-07-21 · Journal Article
- Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors.current
Cao J, Belousoff MJ, Johnson RM, Keov P, Mariam Z, Deganutti G, Christopoulos G, Hick CA, Reedtz-Runge S, Glendorf T, Ballarín-González B, Raun K, Bayly-Jones C, Wootten D, Sexton PM
Nature communications · 2025-04-10 · Journal Article
- AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists.current
Fletcher MM, Keov P, Truong TT, Mennen G, Hick CA, Zhao P, Furness SGB, Kruse T, Clausen TR, Wootten D, Sexton PM
The Journal of pharmacology and experimental therapeutics · 2021-03-16 · Journal Article
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Methodology & citation verification
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