Introduction
AOD-9604 is a synthetic peptide corresponding to amino acids 176–191 of human growth hormone (hGH), with an additional tyrosine residue at the N-terminus to stabilise the peptide. The sequence is Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe, with a disulfide bond between the two cysteine residues that mirrors the structure of the C-terminal region of native hGH.
AOD-9604 was developed by researchers at Monash University in Australia and has been studied primarily for its lipolytic (fat-mobilising) activity. Unlike full-length growth hormone, AOD-9604 does not bind to the growth hormone receptor and does not stimulate IGF-1 production, making it a useful research tool for isolating the fat metabolism effects of the hGH C-terminal region from the broader anabolic and growth-promoting effects of full-length GH.
All AOD-9604 products supplied by Alpha Peptides are intended strictly for in vitro and laboratory research use only and are not approved for human or veterinary administration.
Structure & Background
The lipolytic activity of growth hormone has long been recognised, but the specific region of the hGH molecule responsible for fat metabolism effects was not well characterised until research identified the C-terminal fragment (residues 176–191) as the primary lipolytic domain. AOD-9604 was synthesised as a research tool to study this activity in isolation, without the confounding effects of GH receptor binding and IGF-1 stimulation that accompany full-length GH administration.
The disulfide bond between Cys182 and Cys189 is essential for the biological activity of AOD-9604 and mirrors the structure of this region in native hGH. Researchers should ensure that reconstituted AOD-9604 solutions are handled carefully to avoid disulfide bond reduction, which would inactivate the peptide.
Proposed Mechanisms of Action
- Lipolysis stimulation: AOD-9604 stimulates lipolysis — the breakdown of stored triglycerides in adipocytes into free fatty acids and glycerol — through a mechanism that does not involve the classical GH receptor. Research has proposed that AOD-9604 interacts with a distinct receptor or signalling pathway in adipose tissue that mediates its fat-mobilising effects.
- Lipogenesis inhibition: In addition to stimulating lipolysis, AOD-9604 has been reported to inhibit lipogenesis (the synthesis of new fat from dietary carbohydrates), potentially contributing to a dual mechanism of action on adipose tissue metabolism.
- Beta-3 adrenergic receptor involvement: Some research has proposed that AOD-9604's lipolytic effects involve the beta-3 adrenergic receptor, which is expressed in adipose tissue and plays a role in thermogenesis and fat mobilisation. However, the precise receptor mechanism remains an active area of investigation.
- No IGF-1 stimulation: A key feature of AOD-9604 that distinguishes it from full-length GH is its lack of IGF-1-stimulating activity. This makes it a useful research tool for studying fat metabolism independently of the anabolic and mitogenic effects associated with IGF-1 upregulation.
- Cartilage repair activity: More recent research has investigated AOD-9604 in the context of cartilage repair, with studies reporting chondroprotective effects and promotion of cartilage regeneration in animal models. This activity appears to be independent of its lipolytic mechanism and has opened a new research direction for this compound.
Key Research Findings
Adipose Tissue & Metabolic Research
Preclinical studies in obese rodent models have demonstrated significant reductions in body fat and improvements in metabolic parameters following AOD-9604 treatment, with effects attributed to enhanced lipolysis and reduced lipogenesis in adipose tissue. These findings established AOD-9604 as a research tool of interest for studying the relationship between GH signalling, adipose tissue biology, and metabolic health.
Clinical Research Programme
AOD-9604 progressed through clinical trials conducted by Metabolic Pharmaceuticals in Australia, with Phase II studies in obese human subjects reporting modest but statistically significant reductions in body weight compared to placebo. The compound demonstrated a favourable safety profile in these studies, with no significant effects on blood glucose, IGF-1 levels, or other GH-related parameters — consistent with its lack of GH receptor binding activity. The clinical programme was ultimately discontinued for commercial rather than safety reasons.
Cartilage & Joint Research
More recent preclinical research has investigated AOD-9604 in osteoarthritis and cartilage injury models, reporting chondroprotective effects including reduced cartilage degradation, promotion of proteoglycan synthesis, and improved joint histology in treated animals. This has generated interest in AOD-9604 as a research tool for studying cartilage repair mechanisms, distinct from its original metabolic research context.
Safety Profile in Research
AOD-9604 has been granted GRAS (Generally Recognised As Safe) status by the US FDA for use as a food ingredient — an unusual designation for a research peptide that reflects the extensive safety data generated during its clinical development programme. This safety profile makes it a useful reference compound in metabolic research.
Research Considerations
- The disulfide bond in AOD-9604 is essential for activity. Avoid reducing agents in reconstitution buffers and handle reconstituted solutions carefully to preserve disulfide bond integrity.
- AOD-9604 does not bind the GH receptor and does not stimulate IGF-1 — this is a key distinction from full-length GH and GHRH analogues like Tesamorelin when designing comparative research protocols.
- The cartilage repair activity of AOD-9604 appears mechanistically distinct from its lipolytic activity, and researchers should consider which activity is relevant to their specific research question.
- Refer to the Certificate of Analysis (COA) supplied with each batch for purity and sequence confirmation data.
Reconstitution & Storage
AOD-9604 should be reconstituted with bacteriostatic water to the required concentration. Store the reconstituted solution at 2–8°C and use within 28–30 days. Avoid freeze-thaw cycles of the reconstituted solution. For full guidance, refer to our Peptide Reconstitution Guide and Storage & Handling Guide.
Research Resources
Researchers can source AOD-9604 5mg from Alpha Peptides, supplied with a full batch-specific COA. For related compounds studied in metabolic and growth hormone research, explore our Metabolic Research and Growth Hormone Research collections. For a complementary perspective on GH-axis research, see our Tesamorelin Research Overview.
Disclaimer: All products sold by Alpha Peptides are intended strictly for in vitro research and laboratory use only. They are not approved for human or veterinary use, and this article does not constitute medical advice.
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