AOD-9604
AOD-9604 is a synthetic peptide based on the C-terminal region of human growth hormone, with an added N-terminal tyrosine. It was studied as an anti-obesity agent, but clinical development was discontinued.
Overview
AOD-9604 is a modified fragment of human growth hormone. Research in the 1990s at Monash University in Australia investigated whether the C-terminal region of growth hormone carried its fat-metabolizing effects separately from its growth-promoting and glucose-raising effects. A fragment covering residues 177–191, with an extra tyrosine at the N-terminus, was developed as AOD-9604, with "AOD" standing for anti-obesity drug. The aim was to separate a potential metabolic effect from the broader actions of the full hormone.
AOD-9604 showed effects on fat metabolism in obese rodent models and was taken into human trials for obesity. A larger phase 2b trial did not demonstrate meaningful weight loss compared with placebo, and development for obesity was discontinued. It has since been studied in a limited way in cartilage and joint models. Human evidence of efficacy is lacking, and it is not an approved drug.
Structure
AOD-9604 is a 16-residue peptide consisting of human growth hormone residues 177–191 with an additional tyrosine at the N-terminus (sometimes written as Tyr-hGH 177-191). It contains two cysteine residues that form an intramolecular disulfide bond, creating a small cyclic loop, mirroring the corresponding region of native growth hormone. It is related to, but not identical with, the peptide often called hGH fragment 176-191, and the two should not be assumed interchangeable without checking the sequence.
Mechanism
AOD-9604 was designed to reproduce the lipolytic and anti-lipogenic actions attributed to the C-terminal region of growth hormone. In rodent and in-vitro adipose tissue studies, it was reported to increase fat breakdown and reduce fat synthesis. Notably, it does not appear to bind or activate the growth hormone receptor in the way full-length growth hormone does.
In animal studies it did not raise IGF-1 or produce the insulin-resistance effects associated with growth hormone. The exact receptor or pathway mediating its metabolic effects has not been clearly identified, and some studies have suggested involvement of beta-3 adrenergic signaling in rodents. The mechanism should be regarded as incompletely established.
Research
Obesity in animal models
In genetically obese and diet-induced obese mice and rats, AOD-9604 administration was reported to reduce body fat and weight gain, with effects on lipolysis and lipogenesis in adipose tissue. These rodent findings provided the rationale for clinical development. They come from animal models, and species differences in fat metabolism limit how directly they translate to people. Results across rodent strains were not entirely consistent.
Human obesity trials
AOD-9604 was evaluated in early-phase human studies and then in a larger randomized, placebo-controlled phase 2b trial in adults with obesity. The larger trial did not show a clinically meaningful difference in weight loss compared with placebo, and the developer stopped the obesity program. The studies did provide safety and tolerability data, and no growth hormone-like effects on IGF-1 or glucose were reported.
Cartilage and joint models
Following the obesity program, AOD-9604 was investigated in animal models of osteoarthritis and cartilage injury, sometimes in combination with hyaluronic acid. Some rabbit studies reported effects on cartilage regeneration markers. This work is preclinical and limited in scope, and there is no established human evidence for joint or cartilage effects. Study sizes were small and outcomes were measured histologically or biochemically.
Regulatory status
AOD-9604 is not approved by the FDA for any use and is not an approved drug product in the US. Its status for pharmacy compounding should be checked against current FDA guidance, as its position has been subject to change. Its status in sport is not covered by the categories listed here; check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A COA should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page, and report purity by reverse-phase HPLC. The two cysteines should be present as an intramolecular disulfide: the reduced form differs by 2 Da, and disulfide-linked dimers or oligomers can form during synthesis or storage. Because the peptide is often confused with hGH fragment 176-191, the stated sequence and observed mass should be checked against each other. Methionine oxidation and deletion impurities should also be monitored. Counter-ion and net peptide content should be stated.
Open AOD-9604 in the sequence analyzer to see the expected [M+H]+ and multiply charged ions for an MS identity check (set the N-acetyl, amide and disulfide options to match).
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized AOD-9604 sealed at -20 °C, protected from light and moisture. The disulfide bond can undergo scrambling or reduction in solution, especially at neutral to alkaline pH or in the presence of reducing agents, so avoid thiol-containing buffers. Reconstituted laboratory solutions should be refrigerated, used promptly and aliquoted to avoid repeated freeze-thaw cycles.
Download the AOD-9604 data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention AOD-9604 in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
Is AOD-9604 FDA approved?
No. AOD-9604 is not approved by the FDA for any use. It was studied in human obesity trials, but a phase 2b trial did not show meaningful weight loss compared with placebo, and the obesity program was discontinued. Its status in pharmacy compounding should be checked against current FDA guidance.
What is the difference between AOD-9604 and hGH fragment 176-191?
Both are based on the C-terminal region of human growth hormone. AOD-9604 is hGH residues 177–191 with an extra N-terminal tyrosine, which some descriptions treat as equivalent to fragment 176-191. Because naming is inconsistent, the actual sequence and mass on a COA should be checked rather than relying on the label.
Does AOD-9604 act like growth hormone?
Not in the full sense. AOD-9604 was designed to keep only the fat-metabolizing activity attributed to growth hormone's C-terminal region. In animal studies it did not raise IGF-1 or cause growth hormone-like effects on glucose, and it does not appear to activate the growth hormone receptor in the same way as the full hormone.
Related compounds
- IGF-1 LR3
IGF-1 LR3 is a recombinant analogue of insulin-like growth factor 1 with an arginine substitution at position 3 and a 13-residue N-terminal extension. It binds IGF-binding proteins weakly and is widely used in cell culture.
- Tesamorelin
Tesamorelin is a stabilized synthetic analogue of human growth hormone releasing hormone. It is FDA-approved as Egrifta for reducing excess abdominal fat in adults with HIV-associated lipodystrophy.
- Semaglutide
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy).
- 5-Amino-1MQ
5-Amino-1MQ is not a peptide; it is a small-molecule quaternary quinolinium compound that inhibits the enzyme nicotinamide N-methyltransferase (NNMT). It has been studied in cell and rodent models of obesity and metabolism.
References
- PubMed: all indexed literature on AOD-9604
- ClinicalTrials.gov: registered studies mentioning AOD-9604
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