AOD-9604
AOD-9604 is a synthetic disulfide-bonded fragment of human growth hormone (residues 176-191 plus an N-terminal tyrosine) investigated as an anti-obesity agent that ultimately failed to demonstrate weight-loss efficacy in clinical trials and is not an approved medicine.
AOD-9604 (Advanced Obesity Drug 9604) is a synthetic peptide derived from the C-terminal portion of human growth hormone (hGH). It corresponds to roughly residues 176-191 of hGH with an additional tyrosine added at the N-terminus, and it carries an intramolecular disulfide bond between its two cysteine residues. It was developed by Metabolic Pharmaceuticals (later Calzada Ltd) in Australia as an orally dosed candidate intended to reproduce the fat-metabolizing activity of growth hormone without GH's broader growth-promoting, IGF-1-mediated effects.
Mechanism (as reported in preclinical work). In rodent and ex vivo adipose-tissue models, AOD-9604 has been reported to stimulate lipolysis (fat breakdown) and inhibit lipogenesis (fat formation), with mechanistic studies pointing to beta-3-adrenergic-associated pathways. Investigators have reported that, unlike full-length hGH, it does not appreciably bind the GH receptor or raise circulating IGF-1. These are research findings, not established clinical effects.
Clinical development and outcome. AOD-9604 advanced into human trials for obesity. A pivotal Phase 2b randomized, double-blind, placebo-controlled, multicenter study ("The effect of AOD9604 on weight loss in obese adults") did not meet its primary weight-loss endpoint, and pharmaceutical development for obesity was subsequently discontinued. Reported safety in trials was generally favorable (described as well tolerated, without IGF-1 elevation or notable glucose changes), but this does not establish long-term human safety, and the FDA has noted a lack of evidence supporting effectiveness for obesity.
Regulatory status. AOD-9604 is not an approved drug in any major jurisdiction. In 2014 the FDA issued a "no questions" letter in response to a GRAS (Generally Recognized As Safe) food-ingredient notification (GRN 548) — a food-ingredient determination, not drug approval. On the FDA's interim 503A bulk drug substances list it was placed in Category 2 (substances that may present significant safety risks) in late 2023, then removed from that category in September 2024 after the nomination was withdrawn; after a 4 December 2024 Pharmacy Compounding Advisory Committee review, the FDA recommended against including AOD-9604-related substances on the 503A bulks list. It is on the WADA Prohibited List (class S2, peptide hormones / growth factors) and so is banned in tested sport. Material sold as "AOD-9604" by research-chemical suppliers is unregulated, of variable purity, and labeled not for human or veterinary use.
Chemistry. Sequence H-Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe-OH (16 residues, intramolecular Cys-Cys disulfide); molecular formula C78H123N23O23S2; molecular weight ~1815.1; CAS 221231-10-3; PubChem CID 71300630.
AOD-9604 is a synthetic analog of the C-terminal region (residues ~176-191) of human growth hormone, carrying an added N-terminal tyrosine and an intramolecular disulfide bond. In preclinical and ex vivo adipose-tissue models it has been reported to stimulate lipolysis and inhibit lipogenesis, with mechanistic work pointing to beta-3-adrenergic-associated pathways, while reportedly not engaging the GH receptor or raising IGF-1.
- Human evidence
- Preclinical and early-phase clinical; pivotal Phase 2b obesity trial did not meet its primary weight-loss endpoint
- Regulatory status
- NOT approved as a medicine in any major jurisdiction. Pharmaceutical development for obesity was discontinued after a Phase 2b trial failed to show meaningful efficacy. The FDA issued a "no questions" letter to a GRAS (Generally Recognized As Safe) food-ingredient notification (GRN 548) in 2014, but this is not drug approval. On the FDA's interim 503A bulk drug substances list, AOD-9604 was placed in Category 2 (substances that may present significant safety risks) in late 2023, then removed from that category in September 2024 after the nomination was withdrawn; following a Pharmacy Compounding Advisory Committee review on 4 December 2024, the FDA recommended that AOD-9604-related substances NOT be included on the 503A bulks list, so it is currently neither a Category 2 substance nor an approved 503A bulk drug substance. Listed on the WADA Prohibited List (class S2) for sport. Sold only as a research chemical / not for human or veterinary use.
- Investigational tool for studying growth-hormone-fragment effects on adipocyte lipolysis and lipid metabolism in vitro and in animal models.
- Reference compound for separating GH's putative fat-metabolism effects from its growth-promoting / IGF-1-mediated actions in metabolic research.
- Used in analytical and anti-doping method development as a target peptide on the WADA Prohibited List.
- Failed pharmaceutical development for obesity; in published trials and the FDA's December 2024 Pharmacy Compounding Advisory Committee briefing document, reported clinical-trial safety was described as generally well tolerated with no IGF-1 elevation or notable glucose changes, but long-term human safety is not established and the FDA found a lack of evidence supporting effectiveness for obesity.
- Prohibited in sport under the WADA Prohibited List (peptide hormones / growth factors, class S2); athletes can test positive.
- Not an approved medicine; material sold as a 'research peptide' is unregulated, of variable purity, and not manufactured to pharmaceutical standards.
- No established dosing, route, or safety profile for use in humans or animals outside controlled research settings.
- [1]PubChem Compound 71300630 (AOD-9604)PubChem (NCBI)
- [2]FDA Pharmacy Compounding Advisory Committee briefing document — Evaluation of AOD-9604-related Bulk Drug Substances for 503A inclusion (4 December 2024 PCAC meeting)U.S. Food and Drug Administration
- [3]FDA GRAS Notice Inventory (search GRN 548 for AOD-9604)U.S. Food and Drug Administration
- [4]WADA Prohibited List (peptide hormones / growth factors, class S2)World Anti-Doping Agency