Research Use Only: This product is supplied for laboratory research and in-vitro studies. Not for human or veterinary administration.
AOD9604 6mg
- Synthetic hGH Fragment: 16-amino acid C-terminal peptide (177-191), ≥98% purity
- Beta-3-AR Upregulation: Enhances lipolysis while suppressing lipogenesis without IGF-1 elevation
- Metabolic Research: Six human trials (900+ participants), FDA GRAS status
- Mechanistic pathway studies
- In vitro receptor profiling
- HPLC verified identity and purity
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Research Overview
AOD-9604 (Anti-Obesity Drug 9604) is a synthetic 16-amino acid peptide fragment derived from the C-terminal region of human growth hormone (hGH), corresponding to amino acids 177-191 with an additional N-terminal tyrosine residue. Originally developed in the early 1990s by Professor Frank Ng and colleagues at Monash University in Australia, this peptide was engineered to isolate the lipolytic (fat-metabolizing) properties of growth hormone while eliminating its growth-promoting, diabetogenic, and IGF-1-stimulating effects. Since its development, AOD-9604 has been the subject of over 16 peer-reviewed publications spanning three decades, including six randomized, double-blind, placebo-controlled human clinical trials involving more than 900 participants.
The peptide has been extensively characterized for its effects on adipocyte metabolism, beta-3-adrenergic receptor signaling, and energy expenditure. Unlike full-length growth hormone, AOD-9604 does not bind to the classical hGH receptor, does not elevate IGF-1 levels, and does not impair insulin sensitivity or glucose tolerance. It has been assigned Generally Recognized As Safe (GRAS) status by the FDA for food, beverage, and dietary supplement applications. While clinical development for obesity was discontinued in 2007 after a Phase IIb trial failed to achieve its primary endpoint, the peptide remains a valuable research tool for investigating adipose tissue biology, lipolytic pathways, and receptor-independent signaling mechanisms.
Emerging research has extended interest in AOD-9604 beyond metabolic applications. A 2024 review in Cartilage identified AOD-9604 among key peptides recognized for benefits to bone and joint health, noting its capacity for chondrogenic induction and cartilage regeneration in osteoarthritis models. Subsequently, a 2026 review in the Journal of the American Academy of Orthopaedic Surgeons classified AOD-9604 as a therapeutic peptide for muscle and cartilage repair, noting that it promotes fat metabolism and may support cartilage repair without markedly altering glucose homeostasis or systemic IGF-1 levels.
Primary Research Applications
Mechanism of Action
Beta-3-Adrenergic Receptor Upregulation
Beta-3-AR Expression — AOD-9604 increases beta-3-adrenergic receptor mRNA expression in adipose tissue, restoring receptor levels in obese models to those observed in lean animals. Beta-3-AR knockout mice were completely unresponsive to chronic lipolytic effects, demonstrating that this receptor pathway is essential for sustained fat-reducing activity. When activated, beta-3-AR triggers Gs protein coupling, adenylyl cyclase activation, cAMP production, protein kinase A phosphorylation, and hormone-sensitive lipase translocation to lipid droplets for triglyceride hydrolysis.
Dual Lipolytic and Anti-Lipogenic Activity
Lipid Metabolism Modulation — The peptide exerts a dual metabolic action: enhancing lipolysis (fat breakdown) while simultaneously suppressing lipogenesis (fat synthesis). Oral administration significantly reduces lipogenic activity and increases lipolytic activity in adipose tissue, with concurrent increases in fat and glucose oxidation and elevated energy expenditure. This anti-lipogenic activity is hypothesized to involve inhibition of acetyl-CoA carboxylase, the rate-limiting enzyme in de novo lipogenesis.
Enhanced Fatty Acid Oxidation
Mitochondrial Oxidative Capacity — AOD-9604 substantially increases whole-body fat oxidation with elevated plasma glycerol levels (an index of lipolysis). Unlike full-length growth hormone, AOD-9604 does not induce hyperglycemia or reduce insulin secretion. Enhanced oxidative capacity may involve increased mitochondrial fatty acid uptake via carnitine palmitoyltransferase-1 (CPT-1), enhanced beta-oxidation enzyme expression, and modulation of uncoupling protein expression.
Receptor-Independent Signaling
Non-Classical Pathways — Unlike full-length hGH, which exerts its lipolytic effects through the classical GH receptor and JAK-STAT signaling, AOD-9604 operates through alternative, receptor-independent pathways. The peptide does not compete for the hGH receptor, does not induce cell proliferation, and exerts direct effects on adipocyte metabolism without systemic endocrine disruption or IGF-1 elevation.
“Mechanistic summaries on this page are provided for laboratory reference and should be interpreted within controlled experimental settings only.”
Preclinical Research Summary
In preclinical models, AOD-9604 has demonstrated significant effects on body composition and adipose tissue metabolism. A landmark study by Ng et al. (2000) showed that daily oral administration of 500 µg/kg body weight to obese Zucker rats for 19 days resulted in over 50% reduction in body weight gain (15.8 ± 0.6 g vs. 35.6 ± 0.8 g in controls) with no adverse effect on insulin sensitivity, as demonstrated with euglycemic clamp techniques. Additional studies documented dose-dependent increases in fat and glucose oxidation alongside elevated energy expenditure in multiple murine models.
Critical mechanistic studies by Heffernan et al. (2001) established that both hGH and AOD-9604 increase beta-3-adrenergic receptor mRNA expression in obese mice to levels comparable with lean mice. Beta-3-AR knockout mice were completely unresponsive to chronic lipolytic effects, demonstrating the essential role of this receptor pathway. In cartilage research, a 2015 study in a collagenase-induced knee osteoarthritis rabbit model showed that combined AOD-9604 and hyaluronic acid injections were significantly more effective than either treatment alone, with treated groups showing lower gross morphological and histopathological scores.
Comprehensive safety studies spanning six months in rats (up to 100 mg/kg/day) and nine months in cynomolgus monkeys (up to 50 mg/kg/day) revealed no adverse findings, with NOAEL reaching the highest applied dosages. No genotoxic activity was detected across Ames test, chromosomal aberration assay, and bone micronucleus assay. Pharmacokinetic characterization in porcine models demonstrated an intravenous half-life of approximately 3 minutes, with rapid degradation via sequential amino-terminal amino acid removal and confirmed oral bioavailability.
Academic References
- Natera SH et al. (1994). Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. Biochemistry and Molecular Biology International.
- Ng FM et al. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research in Paediatrics.
- Heffernan MA et al. (2000). Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. American Journal of Physiology - Endocrinology and Metabolism.
- Heffernan MA et al. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology.
- Heffernan MA et al. (2001). Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International Journal of Obesity.
- Stier H et al. (2013). Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism.
- More MI, Kenley D (2014). Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health. Journal of Endocrinology and Metabolism.
- Kwon DR, Park GY (2015). Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Annals of Clinical and Laboratory Science.
- Liao HJ et al. (2024). Peptides for Targeting Chondrogenic Induction and Cartilage Regeneration in Osteoarthritis. Cartilage.
- Rahman OF et al. (2026). Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions. Journal of the American Academy of Orthopaedic Surgeons Global Research & Reviews.
This product is intended exclusively for in vitro laboratory research by qualified professionals. Not for human consumption. Not approved by the FDA.