AOD-9604: Scientific Profile

Publicado el 12 de julio de 2026 · Actualizado el 28 de agosto de 2026

AOD-9604 (CAS 221231-10-3) is a metabolic peptide of 16 amino acids derived from the C-terminal end (residues 177-191) of human growth hormone, with a tyrosine added at the N-terminus. In research models it has been studied for its ability to modulate lipid metabolism (lipolysis and fat oxidation) without the actions on growth or the IGF-1 axis of the full molecule. Material intended exclusively for research use.

AOD-9604 is a synthetic 16-amino-acid peptide corresponding to the C-terminal fragment of human growth hormone (hGH), specifically residues 177-191, to which a tyrosine residue has been added at the amino-terminal end. Hence its formal synonym Tyr-hGH(177-191). Its chemical identity is well characterized: CAS number 221231-10-3, molecular formula C78H123N23O23S2, and a molecular weight of approximately 1815.12 g/mol. The two sulfur atoms in the formula correspond to the two cysteines in the sequence, which form an intramolecular disulfide bridge, a structural feature conserved from the native hGH fragment. The addition of the N-terminal tyrosine was originally introduced to facilitate radiolabeling and tracking of the peptide in laboratory studies, and it was retained in the final molecule.

The compound was developed in the late 1990s and early 2000s by an Australian group (Metabolic Pharmaceuticals), with the aim of isolating the metabolic activity of the C-terminal end of growth hormone, separating it from its somatogenic effects. Full-length growth hormone exerts actions on tissue growth, glucose metabolism, and hepatic IGF-1 production, in addition to a well-known lipolytic activity attributed in large part to its C-terminal region. The working hypothesis that gave rise to AOD-9604 was that this lipolytic domain could be reproduced with a short fragment that, owing to its size and its lack of hGH receptor-binding domains, would not activate the classical growth pathways nor markedly raise blood glucose or IGF-1.

As for the mechanism of action, preclinical research suggests that AOD-9604 favors lipolysis (mobilization of stored triglycerides) and reduces lipogenesis (synthesis and deposition of new fat) in adipose tissue. In animal models and in vitro adipocyte preparations, an increase in lipid oxidation and in the metabolic activity of adipose tissue has been described. Unlike intact growth hormone, in most studies AOD-9604 does not consistently reproduce the effects on cell proliferation or on circulating IGF-1 levels, which constituted the main argument in favor of its "selective metabolic" profile. It is important to emphasize that the exact receptor and signaling cascade responsible for these effects have not been fully defined in the independent literature; the mechanism is better described as a modulation of lipid turnover in the adipocyte than as the activation of a single, validated molecular target. The available data do not support a closed mechanistic explanation, and that nuance should be preserved when describing the compound.

The documented research applications concentrate on the field of energy metabolism and adipose tissue biology. AOD-9604 has been used as a tool to explore the dissociation between the lipolytic activity and the somatogenic activity of growth hormone, that is, to study whether it is possible to induce fat mobilization without stimulating growth pathways. In preclinical models of obesity, its effect on fat mass, body weight, and markers of lipid metabolism has been investigated. Its possible role in the metabolism of cartilage and articular tissues has also been explored in more recent, limited-scope work, although this line of research is exploratory and should not be presented as established. All of this corresponds to experimental laboratory contexts and model studies, not to a validated clinical use.

The level of evidence must be described honestly. AOD-9604 has a reasonable body of preclinical work (studies in rodents and in adipocyte cultures) and was evaluated in clinical trials in humans aimed at obesity. In early phases, metabolic signals of interest were reported, but the clinical program included two oral phase IIb studies—METAOD005, of 12 weeks and 300 subjects, and METAOD006, of 24 weeks, 502 subjects, and doses of 0.25 to 1 mg/day—and the effect on weight observed in the initial trials was not reproduced in the latest and largest one, in which an intensive diet and exercise regimen was incorporated (Stier H, Vos E, Kenley D. J Endocrinol Metab. 2013;3(1-2):7-15, doi:10.4021/jem157w; Moré MI, Kenley D. J Endocrinol Metab. 2014;4(3):64-77, doi:10.14740/jem213w). Its development as a drug for obesity did not progress toward approval. Therefore, although clinical trials in humans did exist, AOD-9604 is not an approved drug and its metabolic efficacy was not robustly demonstrated. As for safety, the studies conducted described generally acceptable short-term tolerability, without marked effects on blood glucose or IGF-1, but there is no body of long-term safety data. For a laboratory, this means treating the compound as a research tool with an uncertain efficacy profile and an incomplete mechanistic characterization.

In summary, AOD-9604 is a metabolic peptide that is well defined from a chemical standpoint, conceived as a functional fragment of growth hormone for the study of lipolysis decoupled from growth. Its interest lies in that conceptual dissociation and in its usefulness as an experimental probe of adipocyte metabolism, always within a strictly research framework and recognizing that clinical evidence of efficacy is limited and inconclusive.