Cagrilintide is a 37-amino-acid, long-acting acylated amylin analogue developed to activate amylin receptors (AMYRs) and the calcitonin receptor (CTR). Its molecular design combines an amylin-derived peptide scaffold with an N-terminal C20 fatty diacid modification, a native-like intramolecular disulfide bond, sequence changes that reduce fibrillation tendency, and C-terminal amidation.

Unlike GLP-1 receptor agonists, cagrilintide acts through the calcitonin receptor family, providing a distinct experimental system for studying amylin signaling, satiety pathways, receptor pharmacology, peptide lipidation, and long-acting metabolic peptide design. Structural studies published in 2025 directly visualized cagrilintide bound to AMY₁R, AMY₂R, AMY₃R and CTR.

Product Information

The FDA Global Substance Registration System identifies cagrilintide under CAS 1415456-99-3 and reports a molecular weight of approximately 4409 Da. PubChem independently reports the same approximate molecular weight.

Cagrilintide Sequence and Structural Design

The mature research sequence is:

{diacid-C20-γ-Glu}KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH₂

Cagrilintide was developed from an amylin/pramlintide-related scaffold, but it is not simply lipidated native amylin. The sequence was engineered to improve physical stability while maintaining potent receptor activity.

A major challenge with human amylin is its strong tendency to form amyloid fibrils. During cagrilintide development, sequence engineering introduced structural features intended to reduce β-sheet-driven aggregation while preserving the receptor-active conformation. Proline residues in the C-terminal region and a charge pair within the central region contribute to this design strategy.

Cys2–Cys7 Disulfide Loop

Cagrilintide contains two cysteine residues forming a single intramolecular disulfide bond between:

Cys2–Cys7

This N-terminal disulfide loop is a characteristic structural feature of amylin-family peptides and was retained during development because disruption of this region substantially compromises receptor potency.

For synthetic material, the oxidized disulfide form should therefore be considered part of the intended molecular identity rather than a secondary QC detail.

Why Cagrilintide Is Lipidated

The N-terminal lysine is modified with a C20 fatty diacid through a γ-glutamate linker.

This acylation increases reversible association with circulating albumin and contributes to prolonged exposure compared with short-acting amylin analogues. Importantly, the lipid is positioned at the N-terminal Lys because structural modeling and subsequent cryo-EM studies showed that this region can accommodate lipidation without disrupting the principal receptor-bound peptide conformation.

Recent structural work comparing cagrilintide with a non-lipidated backbone analogue found that lipidation did not substantially alter the receptor-engaged peptide backbone once the ligand was stably bound. This supports the idea that the lipid modification primarily contributes to pharmacokinetic engineering rather than creating an entirely different receptor-binding geometry.

We think this distinction is important when researchers design cagrilintide analogs: the fatty diacid is a pharmacokinetic design element, but its attachment site and linker chemistry still form part of the defined synthetic molecule.

Amylin and Calcitonin Receptor Pharmacology

Cagrilintide is now better described as a dual amylin receptor and calcitonin receptor agonist rather than simply an “amylin mimetic.”

Amylin receptors are heteromeric complexes formed by the calcitonin receptor together with receptor activity-modifying proteins:

Cryo-EM structures published in 2025 showed cagrilintide bound to active Gs-coupled AMY₁R, AMY₂R, AMY₃R and CTR, confirming direct engagement across this receptor family.

The peptide adopts an amylin-like receptor-binding mode but produces receptor conformational dynamics distinct from some classical amylin and calcitonin ligands. A separate 2025 structural study also identified residues including Phe23 and the central Glu14–Arg17 interaction as contributors to receptor engagement and peptide conformation.

Why the C-Terminal Amide Matters

Cagrilintide terminates with:

–P-NH₂

The C-terminal amide is not simply a generic peptide-stability modification.

During the medicinal chemistry program that produced cagrilintide, investigators found the C-terminal amide to be essential for activity. The C-terminal portion of amylin-family peptides interacts with the extracellular domain of the receptor, making terminal chemistry relevant to receptor recognition.

We therefore consider three structural features particularly important when evaluating synthetic cagrilintide:

C20-γ-Glu lipidation, Cys2–Cys7 disulfide formation, and C-terminal amidation.

A high HPLC purity result cannot compensate for an incorrect form of any of these features.

Research Applications

Cagrilintide can be used in studies involving amylin receptor signaling, calcitonin receptor pharmacology, metabolic pathways, ligand–GPCR interactions, long-acting peptide engineering, lipidated peptide design, peptide aggregation, and structure–activity relationships.

It is also an informative research scaffold for comparing amylin-based biology with GLP-1-based biology, because the two peptide classes act through different receptor systems despite overlapping interest in metabolic research.

Researchers developing modified amylin analogues, alternative fatty-acid linkers, altered lipidation sites, disulfide variants, or related long-acting peptides can explore our Custom Peptide Synthesis capabilities.

Current Clinical Research Context

Cagrilintide remains an investigational molecule, but its clinical development has advanced substantially.

In the original Phase 2 monotherapy study, 706 participants with overweight or obesity were treated for 26 weeks. Cagrilintide produced dose-dependent mean body-weight reductions of approximately 6.0% to 10.8%, compared with 3.0% with placebo. At the 4.5 mg dose, mean weight reduction reached 10.8%, versus 9.0% with once-daily liraglutide 3.0 mg.

More recently, cagrilintide has been extensively studied together with semaglutide as CagriSema.

In the Phase 3 REDEFINE 1 trial, the cagrilintide 2.4 mg + semaglutide 2.4 mg combination produced substantial weight reduction over 68 weeks. The peer-reviewed study was published in the New England Journal of Medicine in 2025.

CagriSema was submitted to the U.S. FDA in December 2025, and Novo Nordisk currently anticipates an FDA decision by late 2026.

Cagrilintide is also being advanced independently. Novo Nordisk reported that cagrilintide 2.4 mg monotherapy produced approximately 11.8% mean body-weight reduction at 68 weeks in a REDEFINE 1 analysis, and the molecule has entered the RENEW Phase 3 program.

These clinical results provide biological context for research applications but should not be interpreted as specifications or performance claims for synthetic research-grade material.

Synthetic and Quality Control Considerations

Cagrilintide is considerably more demanding to manufacture than a conventional unmodified 37-residue linear peptide.

The final molecular form requires correct synthesis of the peptide backbone, site-specific C20-γ-Glu lipidation, intramolecular Cys2–Cys7 oxidation, and C-terminal amidation.

Lipidation also increases hydrophobic character and can change both chromatographic retention and purification behavior. Meanwhile, amylin-derived sequences have historically presented aggregation and physical-stability challenges.

We think final QC should therefore evaluate identity and molecular form together with chromatographic purity, rather than relying on HPLC percentage alone.

Our Peptide Quality Control capabilities include analytical HPLC and mass spectrometry with batch-specific documentation according to the selected product specification.

Purity and Experimental Planning

The appropriate purity depends on the downstream workflow.

For exploratory analytical studies, the required specification may differ from quantitative receptor assays or sensitive cell-based experiments. Counterion content, residual TFA, and endotoxin requirements may also become relevant depending on how the peptide will be used.

Researchers can refer to our Recommended Peptide Purity guidance when planning the required specification.

For a molecule such as cagrilintide, We recommend confirming the lipidated form, oxidation state, terminal amide, molecular mass, and purity specification before the experiment is scheduled.

Frequently Asked Questions

What is cagrilintide?

Cagrilintide is a long-acting acylated amylin analogue designed to activate amylin receptors and the calcitonin receptor. It is being investigated both as a standalone molecule and in combination with semaglutide.

How many amino acids are in cagrilintide?

Cagrilintide contains 37 amino-acid residues. Its peptide sequence is modified with an N-terminal C20 fatty diacid–γ-Glu group and a C-terminal amide.

What is the disulfide bond in cagrilintide?

The native cagrilintide peptide contains one intramolecular disulfide bond between Cys2 and Cys7 when residues are numbered from the N-terminal Lys of the peptide backbone.

Is cagrilintide a GLP-1 receptor agonist?

No. Cagrilintide acts primarily through amylin receptors and the calcitonin receptor, not through GLP-1R. In CagriSema, cagrilintide supplies the amylin-receptor component while semaglutide provides GLP-1 receptor agonism.

Why is cagrilintide combined with semaglutide?

The combination is designed to engage two complementary signaling systems: amylin/CTR-family signaling through cagrilintide and GLP-1R signaling through semaglutide. This differs mechanistically from a single peptide acting at both receptors.

Is cagrilintide FDA approved?

Cagrilintide itself remains investigational as of August 2026. The fixed-dose cagrilintide/semaglutide combination CagriSema was submitted to the U.S. FDA in December 2025, with a regulatory decision anticipated in late 2026.

Research Use Only

Cagrilintide is supplied for research use only. It is not intended for therapeutic, or human use.