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CAGRINILTIDE 10MG research vial, 3rd Rock Compounds

Front label

Metabolic | >99.80% purity

CAGRINILTIDE 10MG

Cagriniltide (also known as AM833 or NN1213 ) is a novel, investigational, long-acting acylated analogue of human amylin (islet amyloid polypeptide, IAPP) developed by Novo Nordisk.

$110

Lot

CG26C010

Purity (HPLC-UV/VIS)

>99.80%

Lab

Vanguard Laboratory

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Issued by Vanguard Laboratory, A2LA #6377.01.01. Testing was commissioned by our fulfilment partner on the material we ship; the certificate names that party, not 3rd Rock Compounds.

Quantity

CAGRINILTIDE 10MG

1 vial · $110

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Identifiers

CAS number
1415456-99-3
Molecular formula
C₁₉₄H₃₁₂N₅₄O₅₉S₂
Molecular weight
4409.01 Da
PubChem CID
171397054
Sequence
K(Eicosanedioic acid-γ-Glu)-CNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH₂

Mechanism of Action

Cagriniltide functions as a non-selective dual agonist of both calcitonin receptors (CTR) and amylin receptors (AMY1R, AMY2R, AMY3R) — heterodimers of CTR with RAMPs 1, 2, or 3.[3][12]

Receptor Targets & Binding

TargetInteractionEvidence
Calcitonin Receptor (CTR)Non-selective agonist; class B1 GPCR; EC50 62 pMKruse et al. (2021); Cao et al. (2025) cryo-EM[3][9]
AMY1R (CTR+RAMP1)Potent agonist; "bypass" conformation bindingRAMP1/3 KO abolishes weight-loss effects[8]
AMY3R (CTR+RAMP3)Potent agonist; EC50 49 pM (hAMY3R)Carvas et al. (2025): essential for efficacy[8][13]
CGRPR / AM1R / AM2RNo or very low activity — selective for amylin/calcitonin axisFletcher et al. (2021)[12]

Downstream Signaling

PathwayEffectConsequence
Gs / Adenylyl Cyclase / cAMPGs-protein activation → adenylyl cyclase → intracellular cAMP accumulationPrimary signaling cascade for satiety[9]
Neuronal cFos (AP/NTS/LPBN)Induces cFos expression in area postrema, nucleus of solitary tract, lateral parabrachial nucleusSatiety signaling; 57% fewer AP neurons in RAMP1/3 KO[8]
Gastric EmptyingDelays gastric emptying → prolonged postprandial fullnessReduced caloric intake; may affect oral drug absorption
Glucagon SuppressionSuppresses postprandial glucagon from pancreatic α-cellsImproved glycemic control without hypoglycemia risk[6]

Unique Binding Characteristics

PropertyCagriniltideSalmon Calcitonin
Receptor Conformation"Bypass" (stabilized by ionic lock N14E–V17R)"CT-like" conformation
Residence Time3–6 minutes (rapid dissociation)45–60 minutes (slow dissociation)
DesensitizationPrevents receptor downregulation → sustained weight lossCauses receptor downregulation → weight regain

RAMP Dependence: Carvas et al. (2025) demonstrated that the weight-lowering and anorectic effects of cagriniltide are strictly dependent on AMY1R and AMY3R — knockout of RAMP1 and RAMP3 completely abolished drug efficacy, with 57% fewer neurons activated in the area postrema.[8]

Cryo-EM Structural Insights

Cao et al. (2025) and Gu et al. (2026) resolved the cagriniltide-bound calcitonin-receptor and amylin-receptor cryo-EM structures, revealing the distinct "bypass" binding conformation stabilized by the engineered N14E-V17R ionic lock. Unlike salmon calcitonin (which adopts a deep "CT-like" pose with prolonged residence time and progressive receptor desensitization), cagriniltide engages the receptor extracellular domain in a more shallow, dynamic geometry that produces full Gαs-coupled cAMP signaling but allows rapid dissociation. This kinetic difference appears to be the molecular basis for the durable weight-loss response observed across the REDEFINE program — the receptor remains responsive to repeat dosing rather than progressively downregulating.[9][10]

Hindbrain Satiety Circuitry

The principal central site of action is the area postrema (AP), a circumventricular organ outside the blood-brain barrier where AMY1R/AMY3R-expressing neurons project to the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (LPBN). cFos mapping studies show robust neuronal activation across this AP→NTS→LPBN→hypothalamic axis after subcutaneous cagriniltide; RAMP1/3 knockout eliminates 57% of AP cFos induction and abolishes the anorectic response — establishing AMY1R/AMY3R (rather than the calcitonin receptor in isolation) as the primary therapeutic target.[8] Downstream effects include delayed gastric emptying (prolonged postprandial fullness), suppression of postprandial glucagon from pancreatic α-cells (improved glycemic control without hypoglycemia risk), and reduced caloric intake (-51% over 24 h in mouse food-intake studies at 30 nmol/kg).[6][13]

Synergy with GLP-1 Agonism

Cagriniltide's hindbrain AMYR/CTR target is non-overlapping with the GLP-1-receptor-driven satiety pathway engaged by semaglutide (NTS, ARC, PVN). Co-administration produces additive weight-loss effects exceeding either monotherapy — the molecular substrate for the +6.7-percentage-point CagriSema benefit (22.7% vs 15-16% semaglutide alone) observed in REDEFINE 1. This non-redundant satiety-pathway combination model is now driving exploration of cagriniltide pairings with next-generation incretin agonists.[5][14]

Preclinical Research Findings

Cagriniltide is currently evaluated in late-stage clinical trials across 4+ research domains:

  1. Obesity & Weight Management — CagriSema (cagriniltide + semaglutide) achieved 20.4–22.7% weight loss in Phase 3 REDEFINE 1 trial (n=3,417), significantly outperforming semaglutide monotherapy (15–16%) and cagriniltide monotherapy (11.8%). Targets the "weight loss plateau" seen with single-agent GLP-1 therapy.[5]
  2. Type 2 Diabetes — REIMAGINE 2 trial (n=2,728) demonstrated HbA1c reduction of 1.91% with CagriSema vs 1.76% with semaglutide alone (superiority); 73.5% achieved HbA1c <6.5%. Phase 2 data showed HbA1c reduction of -2.2%.[6][4]
  3. Cardiovascular Risk Reduction — REDEFINE 1 post-hoc analysis showed systolic blood pressure decreased -10.9 mmHg with CagriSema vs -2.1 mmHg placebo. Significant reduction in hsCRP inflammatory markers. Dedicated REDEFINE 3 MACE outcomes trial is ongoing.[7]
  4. Combination Therapy for Resistant Phenotypes — Research explores utility for subjects failing GLP-1 monotherapy or requiring bariatric-surgery-level weight management. Theoretical combinations with next-generation incretin agonists under investigation.[14]
  5. Receptor Pharmacology — Cryo-EM structural biology of dual AMYR/CTR agonism; RAMP-dependent signaling; "bypass" vs "CT-like" receptor conformations; rapid-dissociation kinetics preventing desensitization.[9][10]
  6. Glycemic Control Without Hypoglycemia — Suppresses postprandial glucagon from pancreatic α-cells; delays gastric emptying; complements insulin-sparing effect of GLP-1 agonism in T2D protocols; 73.5% of REDEFINE 2 participants achieved HbA1c <6.5% vs 15.9% on placebo.[6]
  7. Mechanism of Anti-Desensitization — Rapid 3-6 min receptor residence time prevents AMYR/CTR downregulation that historically limits salmon-calcitonin chronic dosing; supports durable weight-loss response across 68-week REDEFINE protocols.[9]

Comparative Research Context

Cagriniltide sits at the intersection of two adjacent neuropeptide-pharmacology research programs: the amylin/calcitonin axis (historically dominated by pramlintide, requiring multiple-daily-dose injections, and salmon calcitonin, limited by receptor desensitization) and the modern incretin program (semaglutide, tirzepatide, and next-generation poly-agonists). The unifying mechanistic story is non-overlapping satiety-pathway combination — AMYR/CTR engagement in the area postrema layered on top of GLP-1R, GIP-R, and glucagon-receptor engagement in the broader hypothalamic-brainstem satiety network. Researchers comparing cagriniltide with related metabolic and incretin compounds commonly cross-reference our Semaglutide and Tirzepatide pages for parallel pharmacology in matched obesity and T2D models. The Carvas 2025 RAMP1/3 knockout, Cao 2025 cryo-EM, and the Kruse 2021 SAR work together establish cagriniltide as the canonical research tool for dissecting AMY1R/AMY3R signaling separately from generic calcitonin-receptor activation.

Safety Profile

Findings summarised above derive from in-vitro and animal studies. No safety profile for human use is established or implied, and none is offered here.

Handle as a laboratory reagent: avoid inhalation and contact, reconstitute under aseptic conditions, and observe the storage conditions below.

For research use only. Not for human consumption.

Shipping and Storage

  • Supplied as lyophilised powder in a sealed vial.
  • Store at 2–8°C (36–46°F). Protect from light.
  • Same-day fulfilment on orders before 2pm; shipping 2–4 business days.
  • For research use only. Not for human consumption.

References

  1. [1]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, 397(10286), 1736-1748, 2021. PubMed →
  2. [2]Lau DCW, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet, 398(10317), 2160-2172, 2021. PubMed →
  3. [3]Kruse T, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of Medicinal Chemistry, 64(15), 11183-11194, 2021.
  4. [4]Frias JP, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet, 402(10403), 720-730, 2023. PubMed →
  5. [5]Garvey WT, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 393(7), 635-647, 2025.
  6. [6]Davies MJ, et al. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. New England Journal of Medicine, 393(7), 648-659, 2025.
  7. [7]Verma S, et al. CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. Hypertension, 83(2), e26055, 2026.
  8. [8]Carvas AO, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine, 118, 105836, 2025.
  9. [9]Cao J, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nature Communications, 16, 3389, 2025.
  10. [10]Gu YM, et al. Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors. Acta Pharmacologica Sinica, 47(1), 162-172, 2026.
  11. [11]Wang Y, Feng Z, Yu L. The next frontier in metabolic health: Cagrilintide-Semaglutide and the evolving landscape of therapies. The Innovation Medicine, 3(3), 100150, 2025.
  12. [12]Fletcher MM, et al. AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists. JPET, 377(3), 417-440, 2021.
  13. [13]Dahl K, et al. NN1213 – A Potent, Long-Acting, and Selective Analog of Human Amylin. Journal of Medicinal Chemistry, 67(14), 11688–11700, 2024.
  14. [14]Becerril S, Frühbeck G. Cagrilintide plus semaglutide for obesity management. Lancet, 397(10286), 1687-1689, 2021. PubMed →
  15. [15]D'Ascanio AM, et al. Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. Cardiology in Review, 32(1), 83-90, 2024.
  16. [16]Mikhail N, Wali S. Cagrilintide Combined with Semaglutide: A New Approach for Treatment of Obesity and Type 2 Diabetes. Clinical Trials and Clinical Research, 2(5), 2023.
  17. [17]Hales CM. Expanding the Treat-to-Target Toolbox for Obesity and Diabetes Care. New England Journal of Medicine, 393(7), 712-714, 2025.
  18. [18]Gadde KM, Allison DB. Long-acting amylin analogue for weight reduction. Lancet, 398(10317), 2132-2134, 2021.
  19. [19]Dehestani B, et al. Amylin as a Future Obesity Treatment. Journal of Obesity & Metabolic Syndrome, 30(4), 320-325, 2021.

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