AOD-9604 (Anti-Obesity Drug 9604) is a synthetic 16-amino acid peptide modelled on the C-terminal fragment of human growth hormone (residues 176-191), with an added N-terminal tyrosine to stabilise the molecule. The C-terminal region of hGH is the locus of its lipolytic activity; AOD-9604 was engineered to isolate this fragment's lipolytic and lipid-mobilisation effects while removing the residues responsible for the growth-promoting and IGF-1-elevating effects of full-length GH. Studied extensively in preclinical adipose-tissue and obesity research models, AOD-9604 holds GRAS status in the US as a food ingredient but is unapproved as a medicinal product.
AOD-9604 mimics the lipolytic activity of full-length growth hormone by signalling through what is hypothesised to be a non-classical GH receptor pathway in adipocytes. Preclinical mechanistic work suggests upregulation of β3-adrenergic receptor signalling in adipose tissue, driving the cAMP/PKA cascade that activates hormone-sensitive lipase and triggers triglyceride hydrolysis — the same downstream mechanism engaged by exercise and adrenergic stimulants.
Critically, AOD-9604 lacks the residues responsible for GH's anabolic and IGF-1-elevating effects. In published preclinical research, dosing does not elevate plasma IGF-1 or stimulate cartilage growth — separating the metabolic from the anabolic axis of full-length hGH.
The compound has been studied in osteoarthritis research as well, where C-terminal hGH fragments demonstrate cartilage-protective activity in joint-injection preclinical models — a separate line of research from the lipolytic indication.
Foundational research conducted in the late 1990s at Monash University (Ng & Bornstein) established that the C-terminal hGH fragment retained the lipolytic activity of full-length GH while losing the diabetogenic and anabolic effects. Subsequent preclinical research in rodent models documented dose-dependent body-fat reduction without IGF-1 elevation.
A 2007 Phase 2b clinical study in obese humans found subjective tolerability and a modest weight-reduction signal, though the effect size was insufficient to support a primary clinical development pathway and the indication was deprioritised in favour of other approaches.
Separate research has documented chondroprotective activity of hGH C-terminal fragments in osteoarthritis preclinical models, with measurable reductions in cartilage degradation markers in joint-injury protocols. This represents a parallel research interest in AOD-9604 distinct from its original obesity-research framing.
Combined with its US GRAS classification and the absence of IGF-1 elevation, AOD-9604 occupies a unique position in metabolic peptide research — a GH-derived compound that engages neither the GH receptor's anabolic effects nor its diabetogenic ones.