Cagrilintide (AM833): A Research Monograph on Amylin Analogue Pharmacology

Native amylin has a problem: it forms amyloid fibrils so readily that it is essentially unusable as a research reagent at any practical concentration. Cagrilintide (development code AM833, also NNC0174-0833) is Novo Nordisk's engineered answer to that constraint - a lipidated, disulfide-cyclised analogue studied at the calcitonin receptor and all three amylin receptor subtypes, with a published structural and trial record that is now genuinely substantial. Kovalabs supplies it strictly as a research reagent; everything below describes what published studies have investigated, not any human use.

Key facts

What exactly is cagrilintide, and is the vial real?

PubChem Compound resolves the name cagrilintide to exactly one record, CID 171397054, with molecular formula C194H312N54O59S2, an average molecular weight of approximately 4409 g/mol, and InChIKey LDERDVMBIYGIOI-IZVMHKDJSA-N. Cross-checking against the IUPHAR/BPS Guide to Pharmacology (ligand 13768) returns the identical formula and InChIKey, the same PubChem CID, and both programme codes AM-833 and NNC0174-0833 alongside CAS number 1415456-99-3. When the name, the code, the structure, the CID and the CAS all triangulate across two independent databases, the identity is reasonably secure.

Two procurement caveats are worth noting. First, the roughly 4409 g/mol figure is the average mass of the free peptide; material sold as the acetate salt under the same name can quote a slightly different mass, so confirm which form a given lot is before matching it against a theoretical mass. Second, the alternate Novo Nordisk programme code NN9838 also appears in the literature for this molecule; AM833 and NNC0174-0833 are the codes carried by the structural and trial records cited below, and a procurement query using NN9838 alone may miss some of the relevant literature.

How is cagrilintide thought to work?

The IUPHAR/BPS Guide to Pharmacology classifies cagrilintide as a non-selective agonist of the calcitonin-family receptors - the calcitonin receptor (CTR) itself and the three amylin receptor subtypes. The receptor biology here is worth explaining because the subtypes are not simple variants: each amylin receptor is a heterodimer in which CTR, a class B G-protein-coupled receptor, pairs with a receptor activity-modifying protein. CTR with RAMP1 forms AMY1R, CTR with RAMP2 forms AMY2R, and CTR with RAMP3 forms AMY3R. The identity of the RAMP partner is what defines the subtype, and that subtype identity turns out to matter for cagrilintide specifically.

The most detailed structural picture comes from Cao and colleagues (Nature Communications, 2025; PMID 40204768), who used cryo-electron microscopy to resolve cagrilintide bound to CTR and to all three amylin receptor subtypes as active, Gs-coupled complexes at map resolutions of 2.2 to 3.0 angstrom. They report that cagrilintide adopts an amylin-like binding mode but induces receptor conformational dynamics distinct from rat amylin and salmon calcitonin, including stabilisation of a bypass motif spanning residues S19 to P25 and an intramolecular ionic interaction between E14 and R17. The C-terminal residue interacts differently with RAMP1, RAMP2 and RAMP3, which the authors link to receptor-subtype-specific behaviour. The functional paired assays used a cAMP-response-element reporter measuring cAMP signalling in cells expressing CTR with or without RAMP1 or RAMP3, and a NanoBRET-based Gs proximity assay reporting Gs coupling. These are molecular signal-transduction endpoints; no value or living-subject outcome is reported here.

Which subtypes cagrilintide actually engages has also been dissected genetically. Carvas and colleagues (eBioMedicine, 2025; PMID 40609154) used a RAMP knockout mouse panel - RAMP1 knockout, RAMP3 knockout and RAMP1/3 double knockout on a 129S2/SvEv background against wild-type littermates - and identified AMY1R and AMY3R as the receptor subtypes engaged. This is reported as animal study design and receptor-subtype identity only; no effect on any living-subject endpoint is asserted.

The medicinal-chemistry rationale sits in Kruse and colleagues (Journal of Medicinal Chemistry, 2021; PMID 34288673), who describe the design programme that produced cagrilintide. Native amylin's high amyloid-fibril propensity was the constraint the engineering addressed; the lipidation and sequence modifications were chosen to produce a stable, long-acting analogue. That is reported as design rationale only.

What has the research actually looked at?

Four registered trials name cagrilintide, ranging from a Phase 1 safety and pharmacokinetics study to a Phase 2 comparison across multiple disease contexts. Each entry below names the study design and the registered primary endpoint only, with no effect, magnitude, direction or benefit asserted. Disease-relevant endpoint names are listed as registered context with no result implied.

• Phase 2 dose-finding (NCT03856047). Lau et al. (The Lancet, 2021; PMID 34798060) reported a multicentre, randomised, double-blind, placebo- and active-controlled, parallel-group study across 57 sites in ten countries with a 26-week treatment period, with the intervention named NNC0174-0833. Its registered primary outcome measure was named as change in body weight (percent) from week 0 to week 26 (registered endpoint name only; no effect is asserted).
• Phase 1b co-administration (NCT03600480). Enebo et al. (The Lancet, 2021; PMID 33894838) described a single-centre, randomised, double-blind, placebo-controlled multiple-ascending-dose study evaluating cagrilintide co-administered with semaglutide over a 20-week schedule. Its registered primary outcome was the number of treatment-emergent adverse events, with named secondary pharmacokinetic endpoints AUC(0-168h) and Cmax.
• Phase 2, type 2 diabetes (NCT04982575). Frias et al. (The Lancet, 2023; PMID 37364590) reported a multicentre, randomised, double-blind, active-controlled, parallel-group, 32-week study comparing co-administered cagrilintide plus semaglutide against each agent alone. Its registered primary outcome was named as change in glycated haemoglobin (HbA1c) from week 0 to week 32 (registered endpoint name only; no effect is asserted).
• Phase 1 thorough-QT study (NCT05804162). Gabe et al. (Diabetes, Obesity and Metabolism, 2024; PMID 39279639) described a randomised, double-blind, placebo-controlled study in healthy participants with a nested oral moxifloxacin positive control. Its registered primary outcome was named as change from baseline in the Fridericia-corrected QT interval (QTcF) (registered endpoint name only; no effect is asserted).

Secondary literature provides background framing. A systematic review and meta-analysis (Dutta et al., 2024; PMID 39676787) pooled randomised trials of cagrilintide and the cagrilintide-plus-semaglutide combination, with named outcomes only. A narrative review (D'Ascanio et al., Cardiology in Review, 2024; PMID 36883831) summarises cagrilintide as a long-acting amylin analogue within its mechanism class. These records are listed here as research context, not as findings a reader should expect. For related receptor-pharmacology context, the retatrutide research post covers a triple-incretin compound on a different receptor axis, and the retatrutide listing and the metabolic research category sit alongside the cagrilintide listing in the catalogue.

How is cagrilintide handled in the laboratory?

Cagrilintide is supplied as a lyophilised powder. The dry lyophilised state is the most stable storage form: unopened vials are commonly kept frozen at around -20 C, protected from light and moisture, and reconstituted only when bench work begins. For reconstitution as a sample-preparation step, an appropriate laboratory solvent is added slowly down the inner vial wall rather than directly onto the powder, and the solid is allowed to dissolve with gentle swirling only - not vortexing or vigorous shaking - to limit foaming, shear and aggregation. Reconstituted solutions are kept refrigerated at about 2 to 8 C for short-term bench use and aliquoted to avoid repeated freeze-thaw. None of this constitutes a preparation method for any use in humans or animals. The general reconstitution guide covers the technique in more depth.

For a lipidated peptide of this size and complexity, purity and identity are the analytically meaningful quality attributes. A certificate of analysis should report purity by reversed-phase HPLC (area-percent) and identity by mass spectrometry matched against the theoretical average mass near 4409 Da and formula C194H312N54O59S2, with the disulfide-cyclised motif and the lipid side chain reflected in that mass check. A vial that quotes the right compound name is not the same as a vial that contains the right compound. Every Kovalabs batch ships with a certificate of analysis so identity and purity can be confirmed for each lot rather than assumed.

How strong is the evidence, really?

Tier one is solid: the molecular identity triangulates across PubChem (CID 171397054) and the IUPHAR/BPS Guide to Pharmacology, with the same formula C194H312N54O59S2, mass near 4409 g/mol and InChIKey, and the structure has been resolved by cryo-electron microscopy at 2.2 to 3.0 angstrom against CTR and all three amylin receptor subtypes. Tier two is the middle ground: the mechanism work is cell-based and animal-based - CRE-reporter and NanoBRET assays, a RAMP knockout mouse panel - and a cell in a dish is not a person. Tier three is the weakest part: the registered trials are cited here for design and endpoint names only, so no human outcome is established in this post. It is not a licensed medicine, and it has not been shown to produce defined outcomes in humans. Curiosity is warranted; certainty is not.

Research use only

Cagrilintide is supplied and described by Kovalabs exclusively as a research chemical for laboratory and in-vitro research. It is not a medicine, not a supplement, and not for human or veterinary use, administration or consumption. Nothing here constitutes medical, therapeutic or dosing guidance, and no clinical benefit of any kind is stated or implied. The published studies referenced are cited only for their design and endpoint names so that researchers can locate the primary literature themselves. Full terms are set out in the research disclaimer.

Frequently asked questions

What is cagrilintide?

Cagrilintide (development code AM833, also NNC0174-0833) is a synthetic, lipidated, long-acting analogue of the peptide amylin. It is studied as a non-selective agonist at the calcitonin receptor and the amylin receptor subtypes. Kovalabs supplies it strictly as a research reagent, not for human or veterinary use.

What molecular identifiers does cagrilintide carry?

It resolves to PubChem CID 171397054, CAS number 1415456-99-3 (free peptide), molecular formula C194H312N54O59S2, an average molecular weight of approximately 4409 g/mol, and InChIKey LDERDVMBIYGIOI-IZVMHKDJSA-N. These identifiers are cross-checked between PubChem and the IUPHAR/BPS Guide to Pharmacology, which list the same formula and InChIKey for the same compound.

What receptors has cagrilintide been studied at?

It has been characterised at the calcitonin receptor (CTR) and at all three amylin receptor subtypes. Each amylin receptor is a heterodimer of CTR with a receptor activity-modifying protein: CTR plus RAMP1 is AMY1R, CTR plus RAMP2 is AMY2R, and CTR plus RAMP3 is AMY3R. Cryo-EM work has resolved cagrilintide bound to all of these as active, Gs-coupled complexes.

Why is cagrilintide a lipidated analogue rather than native amylin?

The medicinal-chemistry literature (Kruse et al., 2021) describes native amylin as having a high propensity to form amyloid fibrils. Cagrilintide was engineered as a stable, lipidated, long-acting analogue addressing that physical-stability constraint. This is reported as design rationale only.

How should cagrilintide be stored and reconstituted in the laboratory?

As general bench handling of a research reagent only. The lyophilised powder is the most stable form and is commonly kept frozen at around -20 C, protected from light and moisture. For reconstitution, an appropriate laboratory solvent is added slowly down the vial wall with gentle swirling, not vortexing, and reconstituted solutions are usually kept refrigerated at about 2 to 8 C and aliquoted to avoid freeze-thaw cycles. These are generic figures; validate exact storage against the supplier certificate of analysis for the specific lot.

Is cagrilintide approved for any use?

No. Kovalabs supplies cagrilintide solely as a research chemical for in-vitro and laboratory research. It is not a medicine and is not for human or veterinary use. The trials cited above are referenced only for their study designs and registered endpoint names, with no outcome stated or implied.

Sources

1. PubChem Compound: cagrilintide, CID 171397054 (NCBI)
2. IUPHAR/BPS Guide to Pharmacology: cagrilintide, ligand 13768
3. Cao J et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nature Communications, 2025. PMID 40204768; DOI 10.1038/s41467-025-58680-y
4. Carvas AO et al. Brain amylin receptor subtypes engaged by cagrilintide (RAMP knockout mouse panel). eBioMedicine, 2025. PMID 40609154; DOI 10.1016/j.ebiom.2025.105836
5. Kruse T et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of Medicinal Chemistry, 2021; 64(15):11183-11194. PMID 34288673; DOI 10.1021/acs.jmedchem.1c00565
6. ClinicalTrials.gov NCT03856047 (Phase 2 dose-finding; Lau et al., The Lancet 2021, PMID 34798060)
7. ClinicalTrials.gov NCT03600480 (Phase 1b co-administration; Enebo et al., The Lancet 2021, PMID 33894838)
8. ClinicalTrials.gov NCT04982575 (Phase 2, type 2 diabetes; Frias et al., The Lancet 2023, PMID 37364590)
9. ClinicalTrials.gov NCT05804162 (Phase 1 thorough-QT; Gabe et al., Diabetes Obesity and Metabolism 2024, PMID 39279639)