Cagrilintide (AM833)

Long-Acting Amylin Analogue | Non-Selective AMY Agonist

The 4Balance Codex: The Hindbrain-Targeted Satiety Architect and Metabolic Modulator.

Product Overview

Cagrilintide (AM833) is a novel, investigational long-acting acylated analog of human amylin (islet amyloid polypeptide), a hormone co-secreted with insulin by pancreatic beta-cells. It functions as a potent, non-selective agonist across amylin receptor subtypes (AMY1, AMY2, AMY3) and the calcitonin receptor (CTR). Through strategic fatty-acid acylation, this peptide overcomes the rapid degradation typical of endogenous amylin. It is the premier research tool for investigating sustained, central nervous system-mediated satiety signaling pathways that are distinct from, yet complementary to, GLP-1 receptor agonism.

Format: Lyophilized Powder Options: 5mg Vial / 10mg Vial Classification: Acylated Amylin Receptor Agonist

Mechanism of Action: Central Signaling & Protraction

Cagrilintide’s efficacy in metabolic research stems from its specific neural targeting and engineered pharmacokinetics.

1. Hindbrain Receptor Targeting: Unlike GLP-1 analogs that act primarily on the hypothalamus and brainstem, Cagrilintide targets specific neurons in the hindbrain—specifically the area postrema (AP) and the nucleus of the solitary tract (NTS). It binds to heterodimeric amylin receptors (complexes of the Calcitonin Receptor and Receptor Activity-Modifying Proteins, or RAMPs).

2. Induction of Satiety: Activation of these central pathways enhances satiety signals, reduces hunger, and curtails food-seeking behavior independent of the incretin system.

3. Gastric & Glucagon Modulation: Peripherally, Cagrilintide slows gastric emptying, which blunts postprandial glucose spikes, and acts on pancreatic alpha-cells to suppress postprandial glucagon secretion, further improving glycemic control.

4. Albumin Bioconjugation (Protraction): The peptide is modified with a C20 fatty diacid chain via a hydrophilic linker. This modification allows for reversible, high-affinity binding to serum albumin, shielding the peptide from enzymatic degradation and renal clearance, thereby extending its elimination half-life significantly in research models.

Research Applications

In the 4Balance Research Array, Cagrilintide is utilized to explore metabolic pathways beyond standard GLP-1 therapies.

• Synergistic Obesity Models (The "CagriSema" Pathway): The primary research application involves combining Cagrilintide with GLP-1 receptor agonists (such as Semaglutide) to investigate additive or synergistic weight loss effects. This "dual-pathway" approach targets both hindbrain (amylin) and hypothalamic/hindbrain (GLP-1) satiety centers simultaneously for profound body weight regulation.

• Non-Incretin Metabolic Regulation: Investigating glucose homeostasis in models where GLP-1 receptors are desensitized or ineffective, focusing on Cagrilintide's ability to lower blood glucose via glucagon suppression and delayed gastric emptying.

• Neuroendocrine Mapping: Used as a selective probe to map specific neuronal populations in the brainstem responsible for anorexigenic (appetite-suppressing) signaling.

Technical Specifications

• Mass: Available in 5mg or 10mg vials

• Sequence Modification: Human amylin analogue acylated with a C20 fatty diacid

• Solubility: Water Soluble (Requires Bacteriostatic Water for reconstitution)

• Storage: Store lyophilized at -20°C.

References

1. Kruse, T., et al. (2021). The long-acting amylin analogue cagrilintide, developed for treatment of obesity and type 2 diabetes, results in significant weight loss and improvement in glycemic control in obese and diabetic rats. Journal of Medicinal Chemistry.

2. Enebo, L. B., et al. (2021). Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide in subjects with overweight or obesity: a randomised, controlled, phase 1b trial. The Lancet.

3. Hay, D. L., et al. (2015). Amylin receptors: molecular composition and pharmacology. Biochemical Society Transactions.

4. Frias, J. P., et al. (2023). Efficacy and safety of co-administered cagrilintide and semaglutide (CagriSema) in people with type 2 diabetes: a randomised, double-blind, controlled phase 2 trial. The Lancet Diabetes & Endocrinology.

5. Boyle, C. N., et al. (2018). Amylin's primary action in the brain is neuroendocrine, not anorexigenic. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.

DISCLAIMER: FOR RESEARCH USE ONLY. This product is a laboratory reagent intended strictly for in-vitro research and development. It is not for human consumption, veterinary use, or therapeutic application. Bodily introduction of any kind is strictly prohibited by law.