Cagrilintide: Acylated Amylin Analogue Structure, Receptor Logic and Research Use

Cagrilintide is a lipidated, long-acting version of amylin — the hormone that pancreatic beta cells release together with insulin — engineered to be stable and to act broadly across the amylin/calcitonin receptor family. What makes it valuable in metabolic research is that it signals through a route entirely distinct from the incretin receptor family, so it is the standard tool for testing what the amylin system contributes beyond GLP-1 signalling. We supply research-grade cagrilintide freeze-dried in sealed vials, for laboratory use only.

Cagrilintide is still an investigational compound. No regulator anywhere had authorised it for marketing by 2026, and what we sell is a laboratory reference substance, not a medicinal product.

Defining cagrilintide

The natural hormone — human amylin, also called IAPP — is a 37-amino-acid peptide co-released with insulin after meals. As a research tool it is close to useless for two reasons: its half-life in plasma measured in minutes, and its strong propensity to clump into amyloid, the very material that accumulates in pancreatic islets in type 2 diabetes. Any practical analogue must fix both flaws at once. The earlier analogue pramlintide tackled the clumping by copying prolines from the rat sequence (rat amylin never fibrillates), yet it remained short-acting. Cagrilintide (AM833 in early papers) deals with both issues: its sequence resists fibril formation, and a lipid chain attached to it binds albumin, stretching its duration to several days.

Origin and structure

• A backbone based on amylin, carrying substitutions that disrupt the stacked beta-sheets responsible for amyloid formation.
• A disulfide bond within the molecule, joining the two cysteines near the N-terminus. That small ring is required for receptor activity in native amylin and in calcitonin alike, and it is why the formula contains two sulfur atoms.
• An amidated C-terminus, as in native amylin, required for receptor engagement.
• A fatty acid attached to a lysine side chain, giving the reversible albumin binding behind the long circulating presence reported in pharmacokinetic work.
• Activity spread across the family rather than concentrated: reports describe agonism at AMY1, AMY2 and AMY3, and at the calcitonin receptor as well.

Catalogue identifiers: CAS 1415456-99-3, formula C194H309N55O59S2, molecular weight 4409.07 Da.

The proposed mechanism

Unlike a typical GPCR, an amylin receptor is built from two proteins. The calcitonin receptor (CTR) pairs with a receptor activity-modifying protein — RAMP1 gives AMY1, RAMP2 gives AMY2, RAMP3 gives AMY3. The accessory RAMP alters the ligand pocket so that CTR switches its preference from calcitonin to amylin. For assay design this has a direct consequence — a cell line transfected with CTR alone lacks any true amylin receptor, and the pharmacology you measure depends on which RAMP is present.

Signalling is described as Gs-mediated cAMP production. The key receptor populations sit in the area postrema and the nucleus of the solitary tract, hindbrain regions not fully shielded by the blood–brain barrier. In preclinical work, amylin receptor agonists reduce feeding and slow stomach emptying, and these effects are generally attributed to those hindbrain sites. Because this circuit is anatomically and pharmacologically separate from the GLP-1 receptor populations in the hypothalamus and vagus, animal studies report that amylin and GLP-1 agonists add to one another rather than duplicating each other — the rationale for studies pairing cagrilintide with semaglutide.

Receptor selectivity in this family is still an unsolved design question. A ligand that activates AMY1, AMY2, AMY3 and CTR equally produces a blended response, and CTR activation carries its own effects, in bone among other tissues. More selective analogues of amylin are being developed specifically to separate these contributions. A lab choosing cagrilintide should therefore be clear that it reports on broad amylin-family agonism, not on AMY3 alone. To attribute an effect to one subtype, use defined-RAMP cell lines expressing recombinant receptors together with subtype-selective comparator compounds.

What has been studied

• Receptor pharmacology. Binding and cAMP readouts in cells expressing CTR plus RAMP1, 2 or 3, which establish the non-selective profile that distinguishes cagrilintide from subtype-selective amylin analogues.
• Biophysics and aggregation. Thioflavin T fibril assays, circular dichroism and stability studies — core methods for any amylin analogue, because a tendency to aggregate is the family's characteristic weakness.
• Animal work. Feeding, gastric emptying and body-composition measurements in diet-induced obese rodents, plus combination studies testing whether effects add up with GLP-1 receptor agonists.
• Clinical trials. Results from phase 1 and 2 studies are in print, covering cagrilintide alone and co-formulated with semaglutide, and phase 3 programmes have also reported. These concern an investigational medicine given under clinical supervision and have no bearing on research-grade material. For the logic of the combination, see the article explaining why the two are so often studied together.

One practical warning applies to all amylin research. At the low-nanomolar concentrations typical of receptor assays, a lot of peptide sticks to glass and polypropylene — and on a dose–response curve, material lost to the walls is indistinguishable from weak potency. The usual remedies are a carrier protein in the buffer, low-retention plastics and dilutions prepared immediately before use. Skipping them is a common reason why potency values reported for amylin analogues vary by ten-fold or more between laboratories, even when the compound and receptor construct are nominally identical.

Presentations available

The cagrilintide product page lists current sizes and prices. We file it in the GLP-1 and incretin peptides collection, since most buyers use it in incretin comparison studies.

Reconstitution and storage at the bench

The concentration maths is standard: 2 mL of bacteriostatic water added to a 5 mg vial gives 2.5 mg/mL (2,500 mcg/mL), so 0.1 mL contains 250 mcg. Handling, however, needs more care than a typical lipidated peptide. Even after engineering, amylin-family sequences retain some urge to aggregate, and shaking, very dilute solutions in untreated plastic, and a pH near the isoelectric point all encourage that. Add the diluent slowly down the vial wall, swirl rather than shake, and inspect for cloudiness or fibres before use. In an amylin analogue, haze means the preparation has failed — it is not a cosmetic issue.

Unopened freeze-dried vials are stable at −20 °C if kept dry and dark. Hold reconstituted solution at 2–8 °C and use it within the study window. Since aggregation progresses with both time and temperature, keeping the interval between reconstitution and use short is more important here than for incretin peptides. See our reconstitution guide, storage guide.

Purity, the COA and how to read it

For cagrilintide, the certificate needs an HPLC trace with its main-peak area percentage, mass-spec confirmation against the calculated 4409.07 Da, net peptide content, the lot number and the analysis date. There is one molecule-specific check as well. The disulfide bond has to be correctly closed, yet a reduced or wrongly bridged version is just two mass units away from the right structure — a gap a low-resolution instrument can easily miss. If disulfide integrity is critical for your experiment, ask exactly what the analysis was able to resolve. Everything else is explained in our guide to interpreting a certificate of analysis.

A final word on how prepared working solutions are kept. Of all peptide classes, amylin analogues are the one where the delay between making a solution and using it most dependably shows up in the results: aggregation is too slow to see when the solution is made but far enough along to matter a few hours later. Labs that record the preparation time alongside the experiment time, and that remake any solution older than its validated window instead of reusing it, remove a source of drift that is easily misread as biological variation. The same habit explains a good share of the inconsistency between amylin studies from different groups.

Regulatory position

As of 2026, cagrilintide is an investigational substance without marketing authorisation anywhere. The published clinical results describe a trial medicine and do not create any pathway to human use for laboratory material.

Related peptides and comparisons

Most often it is studied together with a GLP-1 receptor agonist — see cagrilintide vs semaglutide. If you are comparing amylin analogues, pramlintide, the short-acting earlier compound, belongs in the set too. For molecules covering several incretin receptors at once, look at retatrutide.

Matching catalogue section: GLP-1 & Incretin Peptides