AOD-9604 is a synthetic peptide analogue derived from the C-terminal region of human growth hormone, engineered to isolate and study the fat-metabolizing properties of HGH without the anabolic and mitogenic effects associated with the full-length hormone. Originally developed by metabolic researchers at Monash University in Australia, AOD-9604 progressed through multiple clinical trials — reaching Phase IIb studies in human obesity research — making it one of the most clinically evaluated HGH-derived peptide fragments in the research literature.
For researchers investigating lipolytic mechanisms, adipose tissue biology, and the separation of HGH’s metabolic from its growth-promoting effects, AOD-9604 provides a well-documented tool compound with a defined receptor pharmacology, a clinical trial dataset, and a clear mechanistic rationale derived from decades of HGH fragment research.
AOD-9604 (Anti-Obesity Drug 9604) is a 16-amino acid peptide corresponding to the C-terminal residues 177–191 of human growth hormone with an additional tyrosine residue added at the N-terminus (making it technically Tyr-hGH[177-191]). This tyrosine addition was incorporated during development to enhance the peptide’s stability and, in early research, to explore oral bioavailability — though the compound has primarily been studied in parenteral form in both preclinical and clinical research.
The structural relationship between AOD-9604 and HGH Fragment 176-191 is close but distinct: both are derived from the same C-terminal region of HGH and share similar lipolytic properties, but AOD-9604’s N-terminal tyrosine modification gives it a slightly different sequence and research profile. AOD-9604 is supplied as a white lyophilized powder, is water-soluble, and reconstitutes readily in bacteriostatic water for research applications.
| Property | Value |
|---|---|
| Full name | AOD-9604 (Tyr-hGH 177-191) |
| Also known as | Anti-Obesity Drug 9604, HGH Frag 177-191 |
| Molecular weight | ~1,815.12 g/mol |
| CAS number | 221231-10-3 |
| Purity (Official Peptides) | >99% by HPLC |
| Physical form | White lyophilized powder |
| Solubility | Water soluble |
| Storage (lyophilized) | 2–8°C, protected from light |
| Storage (reconstituted) | 4°C, use within 30 days |
AOD-9604’s primary research profile centers on its lipolytic activity in adipose tissue — the same fat-metabolizing effect that is attributed to the C-terminal region of full-length HGH but isolated from HGH’s IGF-1-stimulating, anabolic, and mitogenic activities. Research has examined AOD-9604’s effects on fat cell triglyceride mobilization, fatty acid release, and adipocyte signaling in both cell culture and animal models.
Studies in obese rodent models have documented significant reductions in body fat and body weight in AOD-9604-treated groups compared to vehicle controls, with effects observed at doses that produced no measurable changes in IGF-1 levels, glucose metabolism, or lean mass — confirming the separation of lipolytic from growth-promoting HGH activities at the molecular level. Research has characterized the dose-response relationship for fat reduction in these models, with optimal effects observed at doses substantially lower than those required for full HGH’s anabolic effects.
At the cellular level, research has examined AOD-9604’s effects on hormone-sensitive lipase (HSL) activation — the rate-limiting enzyme in triglyceride hydrolysis in adipocytes. Studies in fat cell preparations have reported increased HSL phosphorylation and activity in AOD-9604-treated samples, consistent with the lipolytic mechanism inferred from in vivo observations. The beta-3 adrenergic receptor pathway has been proposed as a mediator of these effects based on inhibitor studies in adipocyte models.
AOD-9604 and HGH Fragment 176-191 are frequently compared in the research literature because they share structural origins in the same C-terminal HGH region and similar lipolytic pharmacology. The key structural difference — the N-terminal tyrosine added in AOD-9604 — affects the peptide’s sequence, isoelectric point, and metabolic stability without fundamentally altering its mechanism of action at adipocytes.
Comparative research has examined whether the tyrosine modification confers meaningful differences in lipolytic potency, duration of action, or oral bioavailability. Early development rationale suggested that tyrosine addition might enable oral activity through different absorption kinetics, but clinical research demonstrated that both fragments are primarily studied through parenteral routes. Researchers choosing between the two for lipolytic mechanism studies should review the specific literature for their model system, as the published preclinical dataset for HGH Fragment 176-191 is somewhat larger, while AOD-9604’s clinical trial data provides additional human pharmacology context.
AOD-9604 is among the few synthetic peptide fragments from HGH to have progressed to Phase IIb clinical trials. The METAOD study program examined AOD-9604 in adult subjects with obesity at multiple dose levels over 12-week and 24-week treatment periods. Results demonstrated a favorable safety and tolerability profile across all dose groups — including no significant effects on HbA1c, fasting insulin, IGF-1, or other growth-related markers — but primary weight reduction endpoints were not met at the doses tested in the general obese population.
The clinical trial data has contributed importantly to understanding AOD-9604’s human pharmacokinetics, receptor interaction profile, and safety boundaries — information that enriches the preclinical research context and informs dose selection for ongoing laboratory studies. Researchers should consult the published METAOD trial reports for detailed pharmacokinetic parameters in human subjects.
Research has explored AOD-9604’s potential applications in metabolic contexts beyond simple obesity models. Studies have examined the compound in metabolic syndrome models, including research on visceral adipose tissue specifically — the depot most strongly associated with cardiovascular and metabolic disease risk — as distinct from subcutaneous fat reduction.
Research has also examined AOD-9604 in models of diet-induced dyslipidemia, where fat mobilization could theoretically affect circulating lipid profiles. Studies in high-fat diet rodent models have reported changes in circulating free fatty acid and triglyceride levels consistent with enhanced adipose lipolysis, providing a link between the cellular mechanism and systemic lipid metabolism endpoints relevant to cardiovascular research.
A less widely appreciated area of AOD-9604 research involves its effects on cartilage metabolism. Studies examining AOD-9604 in osteoarthritis models have reported anti-catabolic effects on articular cartilage — specifically, reductions in markers of cartilage matrix degradation and attenuation of inflammatory signaling in chondrocytes. These observations are attributed to sequence features of the C-terminal HGH fragment region that interact with receptors or signaling pathways expressed in joint tissue independently of the lipolytic mechanisms studied in adipocytes.
Understanding AOD-9604’s mechanism requires appreciation of how the C-terminal region of HGH differs functionally from its N-terminal region. Full-length HGH is a 191-amino acid protein that interacts with its receptor (GHR) primarily through two binding sites — Site 1 in the central and C-terminal regions, and Site 2 in the N-terminal and central regions — to form a 1:2 receptor dimer that activates JAK2/STAT5 signaling and drives IGF-1 production.
The C-terminal fragment (residues ~177-191), which forms the basis of AOD-9604 and HGH Fragment 176-191, retains a beta-sheet structure that interacts with adipocyte surface proteins through mechanisms distinct from the classical GHR dimerization pathway. Research has provided evidence for beta-3 adrenergic receptor involvement in the lipolytic response, as well as direct effects on lipogenic enzymes — suggesting that the fat-metabolizing activity of the C-terminal HGH region operates through pathways that are parallel to, rather than downstream of, the growth-promoting GHR/JAK2 axis. This parallel mechanism explains the observed dissociation of lipolytic and anabolic effects at the pharmacological level.
Disulfide bond integrity: AOD-9604 contains a disulfide bond that is essential for its bioactive conformation. Reducing conditions (DTT, beta-mercaptoethanol) will disrupt this bond and abolish activity. Avoid reconstitution in reducing buffers and confirm that cell culture media used in in vitro studies does not contain reducing agents at concentrations that would reduce the disulfide.
pH sensitivity: The peptide maintains stability over the physiological pH range (6.5–8.0). Avoid extremes of pH during reconstitution and assay preparation. Standard bacteriostatic water (pH ~5.5–7.0) is appropriate for reconstitution.
Dose selection: The dose-response relationship for AOD-9604’s lipolytic effects has been characterized in rodent models. Researchers should review published dose-response data for their specific model species and tissue type, as effective doses in isolated adipocyte models differ from those demonstrating in vivo effects.
Official Peptides supplies research-grade AOD-9604 at >99% purity verified by HPLC and mass spectrometry. Batch-specific certificates of analysis from an independent third-party laboratory are available for every purchase. We ship cold-pack from our US facility with same-day dispatch on qualifying orders.
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Official Peptides supplies research-grade AOD-9604 with >99% HPLC purity and batch-specific COA included. US domestic shipping 2–5 business days. For in vitro research use only.
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