AOD-9604
Synthetic 16 amino acid fragment of human growth hormone (positions 176-191), studied as a selective lipolytic agent.
Also known as: HGH Fragment 176-191, Anti-Obesity Drug 9604
AOD-9604 is a synthetic peptide corresponding to the C-terminal 16 amino acids of human growth hormone (positions 176 through 191). Researchers at Monash University developed it on the hypothesis that this region of HGH contains the fat-mobilizing activity of the full hormone while being structurally separate from the domains that drive growth and raise IGF-1. It was advanced through multiple phases of clinical trials by the Australian biotech company Metabolic Pharmaceuticals before the program was discontinued after a large oral trial failed its primary endpoint.
Key facts
- Class
- Synthetic HGH C-terminal fragment (peptide)
- Sequence
- Positions 176 through 191 of the 191 amino acid human growth hormone sequence
- Originator
- Monash University researchers; clinical development by Metabolic Pharmaceuticals (Australia)
- Regulatory status
- Not approved by the FDA or any regulatory agency for any indication
- GRAS status
- FDA issued a no-objection letter for use as a food ingredient (2014); not a drug approval
What is AOD-9604?
AOD-9604 stands for Anti-Obesity Drug 9604. It is a 16 amino acid synthetic peptide that corresponds to positions 176 through 191 of the 191 amino acid human growth hormone sequence. Because it maps to the C-terminal end of the molecule, it is also referred to in research literature as HGH fragment 176-191.
The compound was developed by researchers associated with Monash University in Melbourne, Australia and subsequently investigated through clinical trials by Metabolic Pharmaceuticals. Some research formulations include an added tyrosine residue at the N-terminus to facilitate radiolabeling; most human trials used the fragment without this addition.
- •Full chemical name: human growth hormone fragment 176-191
- •16 amino acids, derived from the C-terminal end of the 191 amino acid HGH sequence
- •Does not bind the classical GH receptor in the same way as full HGH
- •Does not drive IGF-1 production in published trial data
Proposed mechanism
Full recombinant HGH at pharmacological doses produces lipolysis in adipose tissue. However, it also stimulates IGF-1 production, promotes tissue growth, and can cause insulin resistance, making it unsuitable as a chronic obesity treatment. Preclinical work suggested the fat-mobilizing activity was concentrated in the C-terminal region of the molecule.
The proposed mechanism for AOD-9604 involves beta-3 adrenergic receptor signaling, which activates lipolysis in adipose tissue. Unlike full HGH, the fragment does not appear to activate the downstream signaling cascade that drives IGF-1 production, which is why metabolic disruption was not observed in the published trial data.
- •Proposed lipolytic activity via beta-3 adrenergic receptor signaling
- •Does not activate the full GH receptor cascade responsible for IGF-1 production
- •In vitro and animal studies showed dose-dependent stimulation of fat cell differentiation and lipid breakdown
- •Obese ob/ob mice treated with AOD-9604 showed significantly greater weight loss than placebo controls in preclinical work
Clinical trial history
AOD-9604 progressed through multiple phases of human clinical testing. A Phase 2 trial of the injectable formulation published in the International Journal of Obesity tested multiple doses in obese adults over 12 weeks. The group receiving 250 micrograms per day showed statistically significant fat mass reduction compared to placebo. Higher doses did not produce proportionally greater effects, and IGF-1 levels did not rise meaningfully in any dose group.
Metabolic Pharmaceuticals subsequently developed an oral formulation and advanced it into a large Phase 2b/3 trial designated METAOD006. Enrolling several hundred obese adults across multiple centers, the trial tested the oral compound against placebo over 24 weeks using body weight as the primary endpoint. The trial did not meet its primary endpoint: weight loss in the AOD-9604 arm was not statistically distinguishable from placebo at 24 weeks. The program was discontinued without a regulatory submission.
The gap between the injectable Phase 2 results and the oral Phase 2b/3 outcome likely reflects at least two factors: oral bioavailability of peptides is typically very low without specialized delivery systems, and the 24-week, large-enrollment design was a more demanding test than the earlier injectable work.
Regulatory status
AOD-9604 does not hold an approved drug indication in the United States, European Union, Australia, or any other major regulatory jurisdiction. It was studied through Phase 2b/3 but not submitted for marketing approval after the oral trial failed its primary endpoint.
In 2014, a Generally Recognized as Safe (GRAS) notification for AOD-9604 as a food ingredient was submitted to the FDA. The FDA responded with a no-objection letter for that specific use. This status is sometimes mischaracterized in supplement and research chemical marketing as a form of drug approval. It is not: GRAS applies narrowly to use as a food ingredient at specified levels and says nothing about safety or efficacy as an injectable or oral pharmaceutical.
Material sold as research-grade AOD-9604 is not subject to pharmaceutical manufacturing standards for purity, identity, or sterility. It is intended strictly for laboratory use and is not cleared for human administration.
Research sourcing
AOD-9604 is listed by our research partner, GLP1 Research Lab, which supplies lyophilized peptides for laboratory use. Listings include product identifiers relevant to research documentation.
View AOD-9604 listing at GLP1 Research LabAffiliate partnership. Metabolic Playbook may earn a commission on purchases made through this link at no additional cost to the researcher.