What Is AOD-9604?
AOD-9604 (Anti-Obesity Drug 9604) is a synthetic peptide comprising amino acids 177–191 of the C-terminal end of human growth hormone, with a tyrosine residue added at the N-terminus. It was developed to isolate the fat-metabolizing properties of GH without the anabolic effects of the full-length hormone — particularly without stimulating IGF-1 production or affecting blood glucose levels.
Mechanism of Action
AOD-9604 activates β3-adrenergic receptors and mimics the lipolytic signaling of growth hormone through a distinct receptor pathway from IGF-1. It stimulates lipolysis (breakdown of stored fat) while simultaneously inhibiting lipogenesis (new fat formation). Crucially, it does not produce the insulin resistance, fluid retention, or IGF-1 elevation associated with exogenous GH administration.
Clinical Development History
AOD-9604 advanced to Phase 2b and Phase 3 clinical trials for obesity under the designation Metabical. Trials demonstrated statistically significant reductions in body fat compared to placebo with an excellent safety profile. It is also being investigated in clinical trials for osteoarthritis, where it shows cartilage-regenerative properties independent of its metabolic effects.
Quick Reference
Member reference tables summarize the compound's research parameters.
Research Indications
Research Protocols
As reported in cited literature and research-community logs (see Research Citations below), not a personal dosing recommendation.
This member section describes parameters reported in the research literature.
Peptide Interactions
This member section summarizes reported compound interactions and evidence limitations.
Reported Research Time Points
This member section summarizes reported research time points.
Safety Notes
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
This member section discusses research safety considerations and uncertainties.
Quality Indicators
Research Citations
- Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone
Ng, F.M., Sun, J., Sharma, L., Libinaka, R., Jiang, W.J., Gianello, R., 2000, Hormone Research - Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans
Stier, H., Vos, E., Kenley, D., 2013, Journal of Endocrinology and Metabolism - Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment
Heffernan, M.A., Thorburn, A.W., Fam, B., et al., 2001, International Journal of Obesity - 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
Heffernan, M., Summers, R.J., Thorburn, A., et al., 2001, Endocrinology - Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism
Heffernan, M.A., Jiang, W.J., Thorburn, A.W., Ng, F.M., 2000, American Journal of Physiology - Endocrinology and Metabolism - Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model
Kwon, D.R., Park, G.Y., 2015, Annals of Clinical and Laboratory Science - Detection and in vitro metabolism of AOD9604
Cox, H.D., Smeal, S.J., Hughes, C.M., Cox, J.E., Eichner, D., 2015, Drug Testing and Analysis - Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone
Wu, Z., Ng, F.M., 1993, Biochemistry and Molecular Biology International - Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells
Habibullah, M.M., Mohan, S., Syed, N.K., et al., 2022, Drug Design, Development and Therapy - The 14-Kilodalton Human Growth Hormone Fragment a Potent Inhibitor of Angiogenesis and Tumor Metastasis
Shaker, B.T., Ismail, A.A., Salih, R., et al., 2023, International Journal of Molecular Sciences