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AOD-9604 vs Tesamorelin

Both sit on the growth-hormone axis and both turn up in fat-metabolism research — but one works upstream at the pituitary and the other is a piece of the hormone itself.

Shared research areas:Metabolic
Class16-residue hGH C-terminal fragment analogue with one intramolecular disulfideFull-length 44-residue GHRH analogue with trans-3-hexenoic acid modification
Molecular weight1815.1 g/mol5135.0 g/mol
CAS number221231-10-3Not assigned / not specified
Purity spec≥99%≥99%
Research areasMetabolicHormonal & Endocrine, Metabolic
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 2–3 weeks at 2–8 °C.
Lead degradation routeDisulfide exchange (scrambling) and formation of disulfide-linked dimers, accelerated above about pH 8.Aggregation at air–liquid interfaces from agitation — the practical failure mode for longer chains.
Freeze–thawAliquot on first reconstitution and freeze aliquots once; repeated cycles concentrate peptide at the ice interface and favour intermolecular disulfide pairing.Do not freeze reconstituted material. At this chain length, interfacial aggregation during freezing is a real risk.
Light sensitivityNo specific light requirement beyond normal practice.No specific light requirement beyond normal practice.

How they actually differ

Tesamorelin is a full 44-residue GHRH analogue: it acts at the GHRH receptor and prompts the pituitary to release growth hormone, so the whole GH–IGF-1 cascade follows. AOD-9604 skips the pituitary entirely. It is a 16-residue copy of the C-terminal end of hGH itself (Tyr plus residues 177-191), and in the published human safety data it did not change serum IGF-1. The regulatory paths also diverged: tesamorelin became an approved medicine in the United States, while the AOD-9604 obesity programme was discontinued in 2007 without approval. At the bench, tesamorelin is a long chain that foams and aggregates if shaken; AOD-9604 is short, and the thing to protect is its single disulfide — keep reducing agents and alkaline buffers away from it.

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.

Tesamorelin — origin

Tesamorelin is the complete 44-amino-acid sequence of human growth hormone-releasing hormone with a trans-3-hexenoic acid group attached at the N-terminus. That modification exists for one reason: native GHRH is cleaved almost immediately by dipeptidyl peptidase-4 at the N-terminal end, and the hexenoyl group blocks that cleavage.

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.

Tesamorelin research themes

GHRH receptor agonism

Full-length GHRH activity with DPP-4 resistance conferred by the N-terminal modification.

Visceral adipose tissue

The most distinctive endpoint in its research literature.

GH pulsatility

Studied for effects on endogenous GH secretion patterns rather than direct GH substitution.

Metabolic parameters

Investigated alongside body-composition endpoints in metabolic research.

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.

Tesamorelin handling

  • Allow several minutes for dissolution; do not accelerate with agitation or heat.
  • Swirl gently — long chains aggregate at interfaces.
  • Do not freeze reconstituted solution.

Both third-party tested

Every Popular Peptides batch of AOD-9604 and Tesamorelin 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

Tesamorelin reference

Related comparisons

AOD-9604 and Tesamorelin 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.