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AOD-9604 vs Cagrilintide

AOD-9604 and Cagrilintide are studied in overlapping research areas, which is why they are frequently compared. This is a neutral side-by-side reference drawn from published preclinical literature and laboratory handling data.

Shared research areas:Metabolic
Class16-residue hGH C-terminal fragment analogue with one intramolecular disulfideLipidated 37-residue amylin analogue, Cys2–Cys7 disulfide, C-terminal prolinamide
Molecular weight1815.1 g/molNot specified
CAS number221231-10-3Not assigned / not specified
Purity spec≥99%≥99%
Research areasMetabolicMetabolic
Primary diluentBacteriostatic water (0.9% benzyl alcohol)Bacteriostatic water (0.9% benzyl alcohol)
Working windowCommonly worked with for 2-3 weeks at 2-8 °C in bacteriostatic water.Commonly worked with for 3–4 weeks at 2–8 °C.
Lead degradation routeDisulfide exchange (scrambling) and formation of disulfide-linked dimers, accelerated above about pH 8.Fibrillation — the failure mode specific to this molecular class, and the one its whole design addresses.
Freeze–thawAliquot on first reconstitution and freeze aliquots once; repeated cycles concentrate peptide at the ice interface and favour intermolecular disulfide pairing.Avoid freezing reconstituted material. For an amylin analogue the freeze–thaw concern is not only interfacial aggregation but nucleation of the fibril pathway the molecule was engineered to resist — and fibril formation, once seeded, does not reverse on rewarming.
Light sensitivityNo specific light requirement beyond normal practice.No specific light requirement beyond normal practice.

How they actually differ

Comparing the two: AOD-9604 is 16-residue hgh c-terminal fragment analogue with one intramolecular disulfide, while Cagrilintide is lipidated 37-residue amylin analogue, cys2–cys7 disulfide, c-terminal prolinamide — different molecular classes with different handling consequences; their leading degradation routes differ (disulfide exchange (scrambling) and formation of disulfide-linked dimers, accelerated above about ph 8. for AOD-9604, fibrillation for Cagrilintide), so the storage precautions that matter are not the same; their practical working windows differ once reconstituted. The sections below set out each in full.

AOD-9604 — origin

AOD-9604 is residues 177-191 of human growth hormone with an extra tyrosine added at the N-terminus (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe), closed by a disulfide between the two cysteines. It came out of Frank Ng's group at Monash University in Australia and was developed by Metabolic Pharmaceuticals in Melbourne as an obesity candidate. That programme was discontinued in 2007 after a 24-week phase 2b trial did not show a clinically meaningful outcome, and the compound never reached approval as a medicine.

Cagrilintide — origin

Cagrilintide is an engineered analogue of human amylin (IAPP), the 37-residue hormone co-secreted with insulin from pancreatic beta cells. Its design problem was unusually specific: native amylin is strongly amyloidogenic, readily collapsing from helix into the beta-sheet conformation that seeds fibrils, which is what made a long-acting amylin drug difficult for decades. Cagrilintide carries six substitutions relative to human amylin (14E, 17R, 25P, 28P, 29P, 37P) — roughly 84% sequence homology — plus N-terminal acylation with a C20 fatty diacid through a gamma-glutamate linker.

AOD-9604 research themes

Lipid metabolism in obese and β3-AR knockout mice

Heffernan et al. (Endocrinology 2001) compared hGH and AOD9604 over 14 days in obese mice and in β3-adrenergic-receptor knockout mice. Both raised the repressed β3-AR expression in obese mice, but neither changed body weight or lipolysis in the knockout mice over the long-term protocol, leading the authors to conclude the lipolytic actions were not mediated directly through β3-AR.

Insulin sensitivity in obese Zucker rats

Ng et al. (Horm Res 2000) studied oral administration of AOD9604 in obese Zucker rats, reporting reduced body-weight gain and increased adipose lipolytic activity, and — unlike intact hGH — no impairment of insulin sensitivity on euglycaemic clamp.

Human safety and tolerability data

Stier et al. (J Endocrinol Metab 2013) pooled six randomised, double-blind, placebo-controlled trials and reported no change in serum IGF-1, no adverse effect on carbohydrate metabolism, and no anti-AOD9604 antibodies in tested participants. The same development programme did not show a clinically meaningful weight outcome.

Cartilage in a rabbit osteoarthritis model

Kwon and Park (Ann Clin Lab Sci 2015) gave intra-articular AOD9604, with or without hyaluronic acid, in a collagenase-induced knee osteoarthritis model in rabbits and scored cartilage morphology, histology and lameness.

Cagrilintide research themes

Amylin receptor pharmacology

Cagrilintide binds the calcitonin receptor and all three amylin receptors (AMY1, AMY2, AMY3), which is why the literature sometimes classes it as a dual amylin and calcitonin receptor agonist.

Amyloid-resistant peptide design

A worked example of engineering a fibril-prone hormone into a stable long-acting analogue — salt-bridge helix stabilisation plus beta-sheet-breaking prolines.

Protraction by acylation

The C20 diacid extends the half-life from minutes, for the short-acting analogue pramlintide, to roughly a week.

Combination with incretin agonists

The most-studied context: co-administration with semaglutide, investigated in the REDEFINE trial programme.

AOD-9604 handling

  • Let the vial reach room temperature before opening.
  • Add diluent gently down the vial wall and swirl; do not vortex.
  • Keep reducing agents (DTT, TCEP, β-mercaptoethanol) and alkaline buffers away from the stock.
  • Label aliquots with reconstitution date and diluent.

Cagrilintide handling

  • Never shake. Swirl gently and allow the cake to dissolve in its own time.
  • Do not freeze reconstituted solution.
  • Add diluent down the vial wall rather than directly onto the cake.
  • Treat visible particulate or a settling precipitate as a rejected vial — for an amylin analogue this is the observable end of the fibrillation pathway, not a cosmetic issue.

Both third-party tested

Every Popular Peptides batch of AOD-9604 and Cagrilintide is independently tested by HPLC and LC-MS with a published Certificate of Analysis. Enter a lot number to pull the COA for a specific vial.

AOD-9604 reference

Cagrilintide reference

Related comparisons

AOD-9604 and Cagrilintide are supplied strictly as research chemicals for in-vitro laboratory and research use only. They are not intended for human or animal consumption, diagnostic, or therapeutic use. This comparison summarizes published preclinical literature and laboratory handling data; it is not medical advice, not a claim of efficacy, and not usage guidance.