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AOD-9604 vs GLP-3/RT

AOD-9604 and GLP-3/RT 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 single-chain triple receptor agonist (GIP / GLP-1 / glucagon)
Molecular weight1815.1 g/mol4759.5 g/mol
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 4–6 weeks at 2–8 °C.
Lead degradation routeDisulfide exchange (scrambling) and formation of disulfide-linked dimers, accelerated above about pH 8.Interfacial aggregation from agitation, foaming, or freeze–thaw — the primary practical failure mode for this molecule class.
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 lipidated peptides the freeze–thaw risk is aggregation at the ice–liquid interface rather than chemical breakdown, and aggregation is not reversible 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 GLP-3/RT is lipidated single-chain triple receptor agonist (gip / glp-1 / glucagon) — 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, interfacial aggregation from agitation, foaming, or freeze–thaw for GLP-3/RT), 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.

GLP-3/RT — origin

GLP-3/RT is a rationally engineered single peptide chain designed to activate three receptors at once — GIP, GLP-1, and glucagon. It represents the third generation of incretin design: mono-agonists first, dual agonists such as GLP-2/Tirz second, and triagonists third. Adding glucagon-receptor activity is the conceptual leap, since glucagon signalling contributes energy expenditure rather than only appetite and glycaemic effects.

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.

GLP-3/RT research themes

Triple receptor engagement

The defining feature: simultaneous GIP, GLP-1, and glucagon receptor activity from one chain.

Energy expenditure

Glucagon-receptor activity is studied for its contribution to energy expenditure, distinguishing triagonists from dual agonists.

Glucose regulation

Investigated in metabolic research models for effects on glucose homeostasis.

Body composition in research models

A major focus of the preclinical literature on this compound class.

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.

GLP-3/RT handling

  • Never shake. Foam on a lipidated peptide solution is denatured material at the air–liquid interface, not a cosmetic issue.
  • Introduce diluent slowly down the vial wall and allow the cake to dissolve without agitation, which may take several minutes.
  • Do not freeze reconstituted solution — aggregation from freeze–thaw is irreversible.
  • Faint opalescence at high concentration is expected; visible particulate is not.

Both third-party tested

Every Popular Peptides batch of AOD-9604 and GLP-3/RT 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

GLP-3/RT reference

Related comparisons

AOD-9604 and GLP-3/RT 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.