Cagrilintide
Identification
| Property |
Value |
| Class |
Long-acting amylin analog |
| Molecular Weight |
~4,433 Da |
| Appearance |
White to off-white lyophilized powder |
| Solubility |
Soluble in aqueous buffers at physiological pH |
| Receptor Target |
Amylin receptor (AMY1, AMY3 subtypes); calcitonin receptor (CTR) complex with RAMP1/RAMP3 |
| Half-Life |
~7–10 days (engineered for weekly administration via lipidation and amino acid substitutions) |
Structural & Pharmacological Profile
Cagrilintide is a synthetic amylin analog engineered for extended pharmacokinetics. Native amylin is a 37-amino acid peptide co-secreted with insulin from pancreatic β-cells. Cagrilintide incorporates structural modifications that confer resistance to proteolytic degradation and high-affinity albumin binding, extending its half-life from the native ~13 minutes to approximately 7–10 days.
Key Structural Features
| Feature |
Detail |
| Parent Molecule |
Human amylin (islet amyloid polypeptide, IAPP) |
| Half-Life Extension |
Achieved through lipidation (fatty acid conjugation for albumin binding) and non-proteinogenic amino acid substitutions |
| Amyloidogenicity Reduction |
Amino acid substitutions in the amyloidogenic region (residues 20–29) prevent fibril formation, a known limitation of native amylin |
| Albumin Binding |
Reversible, high-affinity binding to serum albumin reduces renal clearance |
Research Applications
| Research Domain |
Description |
| Satiety & Appetite Regulation |
Amylin receptor activation in the area postrema (hindbrain) induces meal-ending satiety signals; reduces meal size and frequency |
| Gastric Emptying |
Dose-dependent slowing of gastric emptying rate, prolonging postprandial nutrient delivery and enhancing satiety signaling |
| Glucagon Suppression |
Suppresses postprandial glucagon secretion, reducing hepatic glucose output |
| Combination with GLP-1R Agonists |
Investigated in combination with semaglutide (CagriSema); additive or synergistic effects on body weight and glycemic control observed in Phase 2 studies |
| Body Weight Management |
Weight reduction driven primarily by reduced energy intake rather than increased expenditure; distinct mechanism from GLP-1R agonists |
Quality Specifications
| Parameter |
Specification |
Method |
| Purity (HPLC) |
≥99.0% |
RP-HPLC, 214 nm |
| Mass Identity |
MW ±1.0 Da |
ESI-MS |
| Water Content |
≤5.0% |
Karl Fischer titration |
| Peptide Content |
≥80.0% |
Amino acid analysis |
| Counterion |
Acetate (≤1.0% TFA) |
Ion chromatography |
| Endotoxin |
≤1.0 EU/mg |
LAL kinetic chromogenic |
| Residual Solvents |
≤ ICH Q3C limits |
Headspace GC |
| pH (1 mg/mL) |
5.0–7.5 |
Potentiometric |
Available Configurations
| Format |
Size |
Vials per Kit |
| Standard Research Kit |
5 mg × 10 vials |
10 |
| Extended Research Kit |
10 mg × 10 vials |
10 |
| Custom Configuration |
Per project requirements |
Per scope |
Storage & Stability
| Condition |
Requirement |
| Short-term Storage |
2–8°C, lyophilized form |
| Long-term Storage |
−20°C to −80°C, desiccated |
| Reconstituted |
24 h at 2–8°C; aliquot and freeze at −20°C for extended use |
| Shipping |
Cold chain (2–8°C) recommended; ambient ≤7 days |
Documentation
- COA per batch: HPLC purity chromatogram, ESI-MS spectrum, quantitative data
- MSDS per shipment
Special Notes
- FOR LABORATORY RESEARCH USE ONLY.
- Unlike native amylin, cagrilintide is engineered to have minimal fibrillogenic potential. However, researchers should avoid reconstitution in acidic buffers (pH < 4.0) as this may promote aggregation over extended incubation periods.
- Amylin receptor pharmacology is complex due to CTR/RAMP heterodimerization. In vitro binding assays should consider the specific AMY receptor subtype (AMY1 vs AMY3) under investigation.
- For combination studies (e.g., cagrilintide + semaglutide), reconstitute each peptide separately and prepare fresh mixtures immediately before use to avoid potential peptide-peptide interactions in solution.
Key Research References
| Reference |
PMID |
Key Finding |
| Enebo LB et al. "Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial." Lancet. 2021;397(10286):1736–1748. |
33894838 |
Cagrilintide + semaglutide (CagriSema) combination demonstrated additive weight loss with tolerable safety profile; established dual amylin/GLP-1 approach |
| Frias JP et al. "Efficacy and safety of co-administered cagrilintide 2.4 mg and semaglutide 2.4 mg (CagriSema) once weekly in type 2 diabetes: a multicentre, phase 2, randomised controlled trial." Lancet. 2023;402(10403):720–730. |
37364590 |
Phase 2 T2D trial: CagriSema produced superior HbA1c and body weight reductions vs semaglutide alone, confirming amylin/GLP-1 additive pharmacology |
| Kruse T et al. "NN1213 - A Potent, Long-Acting, and Selective Analog of Human Amylin." J Med Chem. 2024;67(18):16867–16884. |
38960379 |
Structural engineering of cagrilintide (NN1213) including lipidation for albumin binding and amino acid substitutions to eliminate amyloidogenicity of native amylin |
Stability & Storage
| Condition |
Degradation Profile |
| Lyophilized Storage |
Standard lyophilized peptide stability. 24 months at 2–8°C, 36 months at −20°C. Desiccated environment essential |
| Neutral pH (5.0–7.5) |
Stable; recommended for reconstitution and working solutions |
| Acidic pH (<4.0) |
May promote aggregation over extended incubation; avoid reconstitution in acidic buffers. Native amylin is known to aggregate at low pH |
| Alkaline pH (>8.0) |
Risk of deamidation and loss of receptor binding affinity |
| Temperature Stress |
The fatty acid conjugate is hydrophobic; mild aggregation possible with temperature fluctuations. Gentle agitation during reconstitution recommended |
| Reconstituted Solution |
24 h at 2–8°C; aliquot and freeze at −20°C for ≤30 days. Avoid repeated freeze-thaw |
Frequently Asked Questions
Q: What purity specifications apply to cagrilintide?
≥99.0% by HPLC at 214 nm with ESI-MS mass identity confirmation (±1.0 Da). Comprehensive QC includes peptide content (≥80.0%), water content (≤5.0%), counterion analysis (acetate, ≤1.0% TFA), and endotoxin testing (≤1.0 EU/mg). Unlike native amylin, cagrilintide's engineered substitutions reduce fibrillogenic potential — but every batch is monitored for aggregation. Full batch-specific COA included.
Q: How should cagrilintide be stored after reconstitution?
Reconstituted cagrilintide is stable for 24 hours at 2–8°C. For longer storage, aliquot into single-use portions and freeze at −20°C (stable ≤30 days). Avoid reconstitution in acidic buffers (pH < 4.0) which may promote aggregation despite the engineered reduction in amyloidogenicity. For combination studies with semaglutide, prepare fresh mixtures immediately before use. Avoid repeated freeze-thaw cycles.
Source & Purchase
For researchers requiring CAGRILINTIDE with full analytical documentation including HPLC and LC-MS traces, visit the PeptideSourceHub product page for bulk pricing and specifications.
Purchase CAGRILINTIDE with COA →
| Product |
Link |
| Semaglutide (GLP-1 RA) |
semaglutide.md — Selective GLP-1 receptor agonist |
| Tirzepatide (Dual GIP/GLP-1) |
tirzepatide.md — Dual GIPR/GLP-1R agonist |
| Retatrutide (Triple Agonist) |
retatrutide.md — Triple GIPR/GLP-1R/GCGR agonist |
| AOD-9604 (hGH Fragment) |
aod-9604.md — Lipolytic hGH fragment 177-191 |