What Is AOD-9604? The hGH 177-191 Fragment Analogue

AOD-9604 is a synthetic 16-amino-acid peptide: residues 177–191 of human growth hormone (hGH) with an additional tyrosine at the N-terminus. Researchers at Monash University developed it to isolate the lipolytic (fat-mobilising) activity attributed to the C-terminal region of hGH, without the hormone’s effects on glucose metabolism. Most published work comes from rodent and adipose-tissue studies in the late 1990s and early 2000s.

For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.

Key points

Sequence: Tyr + hGH(177-191), with a disulfide bond between its two cysteines.
C₇₈H₁₂₃N₂₃O₂₃S₂, 1815.1 g/mol (PubChem).
Rodent studies: increased lipolysis and reduced lipogenesis in adipose tissue.
Did not impair insulin sensitivity in obese rats, unlike intact hGH.
Listed as prohibited in sport; validated detection methods exist.

Quick facts

Property	Value
Sequence	Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe
Disulfide	Cys7–Cys14 (corresponding to the hGH C-terminal loop)
Formula / weight	C₇₈H₁₂₃N₂₃O₂₃S₂, 1815.1 g/mol
Parent	Human growth hormone (191 aa), C-terminal region
Earlier code	AOD-9401 (related analogue in 2000 publication)
Status	Research compound; clinical development for obesity not pursued to approval

Our AOD-9604 research peptide is supplied in 5 mg and 10 mg vials with HPLC and MS data per lot.

Origins: the hGH C-terminal fragment

Growth hormone has metabolic effects on fat tissue as well as growth-promoting effects. In the early 1990s, a synthetic peptide matching hGH residues 177–191 was shown to have antilipogenic activity (Wu et al., 1993). AOD analogues were developed from this region. A 2000 study reported that the related analogue AOD-9401, given orally to obese (ob/ob) mice for 30 days, slowed body weight gain without changing food intake. In ex vivo adipose tissue from obese rodents and humans it reduced lipogenesis and increased lipolysis (Heffernan et al., 2000).

Mechanistic studies

Model	Finding	Study
Obese mice, 14-day intraperitoneal treatment	hGH and AOD-9604 both reduced body weight and body fat and raised beta-3 adrenergic receptor RNA in fat	Heffernan et al., 2001
Beta-3 receptor knockout mice	Chronic effects absent, but acute increases in energy expenditure and fat oxidation persisted; lipolysis not mediated directly via beta-3 receptors	Heffernan et al., 2001
Obese Zucker rats, 19 days oral	Body-weight gain about halved vs control; increased adipose lipolytic activity; no impairment of insulin sensitivity (euglycaemic clamp)	Ng et al., 2000

The insulin-sensitivity result is the main reason AOD-9604 attracted interest: intact growth hormone is diabetogenic with chronic exposure, and the fragment appeared to separate the lipolytic effect from that problem in rodents. Whether this separation holds in other species has not been established in the peer-reviewed literature we reviewed.

Detection and metabolism

An anti-doping laboratory validated a solid-phase extraction method for AOD-9604 in urine with a detection limit of 50 pg/mL. It identified six potential metabolites after incubation in serum and urine, including a stable fragment (CRSVEGSCG) that may extend the detection window (Cox et al., 2015). The paper notes that AOD-9604 is banned by the World Anti-Doping Agency and had been found in confiscated vials.

Handling in the lab

Store lyophilized powder at −20 °C, sealed and dark.
The intramolecular disulfide bond should be preserved: avoid reducing agents (DTT, TCEP) unless intended, and avoid strongly basic solutions.
Water-soluble; reconstitute with bacteriostatic or sterile water and swirl gently. See how to reconstitute AOD-9604.
Confirm identity by MS: the oxidised (disulfide) form is 2 Da lighter than the reduced form.
Calculate concentrations with the peptide reconstitution calculator.

Open questions

Do the rodent findings on lipolysis and insulin sensitivity translate to other species? Peer-reviewed human trial reports are scarce.
What is the receptor or binding partner responsible for the fragment’s activity? It is not the growth hormone receptor in the classical sense, and beta-3 receptor involvement appears indirect.

Related research

Frequently asked questions

What is AOD-9604?

AOD-9604 is a synthetic peptide consisting of amino acids 177–191 of human growth hormone with an extra tyrosine at the N-terminus, 16 residues in total. It was developed to study the lipolytic activity attributed to this region of growth hormone.

What is the difference between AOD-9604 and HGH Fragment 176-191?

Both derive from the C-terminal region of human growth hormone. AOD-9604 is described as hGH 177–191 with an added N-terminal tyrosine; ‘HGH Fragment 176-191’ is named for residues 176–191. In practice the two sequences are very similar, and suppliers sometimes use the names loosely.

How does AOD-9604 work in research models?

In obese mice, AOD-9604 increased lipolytic activity and expression of beta-3 adrenergic receptor RNA in adipose tissue. Its lipolytic effect persisted in beta-3 receptor knockout mice in acute experiments, so it is not mediated directly through that receptor.

Does AOD-9604 affect insulin sensitivity like growth hormone?

In obese Zucker rats, chronic AOD-9604 treatment did not impair insulin sensitivity in euglycaemic clamp studies, in contrast to intact growth hormone.

Is AOD-9604 on the WADA prohibited list?

An anti-doping analytical paper states that AOD-9604 is banned by the World Anti-Doping Agency, and validated urine detection methods exist.

References

Heffernan MA, et al. Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. Am J Physiol Endocrinol Metab. 2000. PMID: 10950816 https://pubmed.ncbi.nlm.nih.gov/10950816/
Heffernan M, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001. PMID: 11713213 https://pubmed.ncbi.nlm.nih.gov/11713213/
Ng FM, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000. PMID: 11146367 https://pubmed.ncbi.nlm.nih.gov/11146367/
Wu Z, et al. Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Biochem Mol Biol Int. 1993. PMID: 8358331 https://pubmed.ncbi.nlm.nih.gov/8358331/
Cox HD, et al. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015. PMID: 25208511 https://pubmed.ncbi.nlm.nih.gov/25208511/
PubChem Compound Summary for CID 71300630, AOD-9604. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/71300630