AOD-9604 is a synthetic peptide based on the C-terminal region of human growth hormone (residues 177-191) with an added N-terminal tyrosine, 16 amino acids in total. It was developed in the 1990s at Monash University to isolate the lipolytic properties of hGH without the growth-related and diabetogenic effects of the full hormone.

What is the amino acid sequence of AOD-9604?

Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe, with an intramolecular disulphide bond present between the two cysteine residues.

Why does AOD-9604 not raise IGF-1 like hGH?

In the reported in-vitro and animal models AOD-9604 showed no growth-hormone-receptor binding or receptor-dependent proliferation, and the clinical trials reported no significant IGF-1 difference. The FDA notes the molecular target and mechanism remain unknown, so the absence of insulin-resistance or tissue-growth effects should be read as model-specific observations, not a proven general property.

What did the clinical trials find?

Development by Metabolic Pharmaceuticals included randomised controlled trials. A 12-week Phase 2 trial reported greater average weight loss than placebo, but the larger 24-week OPTIONS study (536 enrolled) showed no statistically significant weight loss versus placebo at the tested doses, and development as an obesity therapeutic was discontinued around 2007. These are past clinical findings, not a dosing recommendation.

How safe was AOD-9604 in the trials?

Across the sponsor-funded controlled trials (about 893 subjects, oral or intravenous routes) the reported adverse-event profile was similar to placebo, with no statistically significant differences reported in oral glucose tolerance or IGF-1; insulin resistance was not directly excluded. The FDA regards the data as limited, notes unclear causality for some serious events and potential immunogenicity, and points out there are no human subcutaneous or transdermal exposure data. Safety in a trial setting is not approval for human use.

What is the regulatory status of AOD-9604?

AOD-9604 holds no EU marketing authorisation as a medicinal product. A company obtained a self-affirmed GRAS (Generally Recognized As Safe) opinion for it as a food ingredient; the FDA has not made a GRAS determination and it is not in the FDA GRAS notice inventory. GRAS is in any case a food-safety classification, not therapeutic approval. It is intended for research use only, not for human use.

How does AOD-9604 differ from full-length hGH?

AOD-9604 is a 16-amino-acid C-terminal fragment, whereas hGH is a 191-amino-acid hormone. In the reported models AOD-9604 did not bind or activate the growth hormone receptor and was associated with lipolysis but not with IGF-1 elevation. These findings motivated its investigation as a probe of fat metabolism, though the FDA notes its molecular target is unknown, so pathway isolation cannot be assumed.

What is known about AOD-9604 in cartilage research?

In a preclinical collagenase-induced rabbit osteoarthritis model, intra-articular AOD-9604 was associated with improved cartilage regeneration versus saline-treated controls, and a combination with hyaluronic acid performed better than either alone (Kwon and Park, Annals of Clinical and Laboratory Science, 2015). This is preclinical; controlled human cartilage studies are lacking.

What research doses appear in the literature?

The 12-week Phase 2 obesity trial tested oral doses of 1, 5, 10, 20 and 30 mg per day, and the larger OPTIONS trial tested 0.25, 0.5 and 1 mg per day; neither showed convincing efficacy at the tested doses. No approved clinical-use protocol exists, and community self-reported injection figures are unvalidated and not a recommendation.

How should I check AOD-9604 purity and identity?

There is no single guarantee figure. Ask for the batch-specific Certificate of Analysis and check the HPLC purity result, MS identity result and stated test scope for that batch on our /coa page. HPLC peak-area purity alone does not establish identity, content or impurity status.

How is AOD-9604 stored?

Storage conditions should follow the batch-specific validated stability documentation rather than a fixed rule.

Is there human evidence that AOD-9604 causes weight loss?

Not convincingly. The 12-week trial suggested a difference versus placebo, but the larger OPTIONS trial found no statistically significant weight loss at the tested doses and the obesity programme was discontinued. The trials characterised safety signals rather than establishing clinical efficacy.

How can I verify AOD-9604 quality before buying?

Request the batch-specific Certificate of Analysis and confirm that HPLC purity, MS identity and batch number match the received vial. Independent third-party testing (for our batches, Janoshik) is more informative than a general claim.

Is AOD-9604 legal to buy?

AOD-9604 holds no EU marketing authorisation as a medicinal product, and its WADA S2 listing matters in sports contexts. A research-use label does not by itself establish lawful sale: classification and legality depend on presentation, intended use and national law and vary by jurisdiction, and it is not for human use. Confirm the position with the relevant national authority and seek qualified advice.

AOD-9604: What Researchers Should Know About This hGH Fragment

Q: What mechanism is described for its lipolytic effect?

An early mouse-model hypothesis linked its chronic effects to beta-3 adrenergic signalling. Heffernan et al. (2001, Endocrinology, PMID 11713213) reported that in beta-3 knockout mice the chronic lipolytic effect was absent while acute energy expenditure and fat oxidation persisted, and concluded the action was not mediated directly through beta-3 receptors. The FDA states the molecular target and mechanism remain unknown, so these are animal-model findings, not human facts.

Q: What is AOD-9604's WADA status?

AOD-9604 is listed on the World Anti-Doping Agency Prohibited List under peptide hormones, growth factors, related substances and mimetics (class S2). This is relevant for researchers in sports-medicine or exercise-physiology contexts.

AOD-9604 is a synthetic peptide derived from amino acids 177-191 of human growth hormone (hGH). The name stands for "Anti-Obesity Drug 9604". It was developed in the 1990s at Monash University in Melbourne with the goal of isolating the lipolytic effects of hGH without triggering the growth-related and diabetogenic side effects of the full hormone.

AOD-9604metabolic

Modified hGH fragment (177-191) studied for fat metabolism and lipolysis research. Interacts with beta-3 adrenergic receptors without growth-promoting effects.

Structure and Origin

The amino acid sequence of AOD-9604 is:

Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe

AOD-9604 consists of 16 amino acids: residues 177-191 from the C-terminal region of hGH, plus a tyrosine residue at the N-terminus for stabilisation. The disulphide bond between the two cysteine residues (positions 7 and 14) is required for biological activity.

What matters is what the fragment lacks: binding site 2 of the hGH receptor is absent from AOD-9604. This means the peptide cannot dimerise and activate the receptor the way full-length hGH does. This structural property explains why AOD-9604 does not increase IGF-1, does not cause insulin resistance, and does not promote tissue growth.

Mechanism of Action

The lipolytic effect of AOD-9604 operates through beta-3 adrenergic receptors on adipocytes. The signalling cascade leads to elevated intracellular cAMP levels, which in turn stimulates fat breakdown (lipolysis) and inhibits new fat formation (lipogenesis).

In beta-3 receptor knockout mice, the chronic lipolytic effect was absent while acute energy expenditure and fat oxidation persisted, and the authors concluded the action was not mediated directly through beta-3 receptors (Heffernan et al., 2001, Endocrinology, PMID 11713213). The precise molecular mechanism remains unknown.

Selective Action

AOD-9604 was designed to isolate the fat-metabolising properties of hGH. In the reported trials it did not significantly affect blood glucose, insulin sensitivity or IGF-1 levels; broader conclusions about these effects are model-specific.

Clinical Trials

The clinical development of AOD-9604 was driven by Metabolic Pharmaceuticals (Australia). A total of six randomised, controlled studies were conducted.

Phase II Trial (12 Weeks)

In a randomised, double-blind, placebo-controlled 12-week trial, subjects receiving 1 mg/day AOD-9604 lost an average of 2.6 kg body weight, compared to 0.8 kg in the placebo group. An improvement in cholesterol profile was also observed. The safety profile was unremarkable.

Phase IIb Trial (24 Weeks, OPTIONS Study)

The larger OPTIONS study enrolled 536 obese subjects and tested lower doses than the Phase II trial. The result: at the chosen dosages, no statistically significant weight loss versus placebo could be demonstrated. Metabolic Pharmaceuticals discontinued development as an obesity therapeutic in 2007.

Interpreting the Trial Results

The clinical data show a clear pattern: AOD-9604 was well tolerated in the trials (about 893 subjects across six controlled trials), but its efficacy as an oral obesity drug at the tested doses was not convincing. This does not mean the peptide is biologically inactive - rather that the chosen delivery method and dosing were insufficient for clinical approval.

Safety Profile

The safety data for AOD-9604 are unusually extensive for a research peptide. Across all six clinical trials (Phase I, IIa, and IIb) involving about 893 subjects, the following was reported:

No changes in fasting glucose or glucose tolerance
No impact on insulin sensitivity
No elevation of IGF-1
No suppression of the hypothalamic-pituitary axis
No effects on thyroid function or reproductive hormones
Adverse event profile indistinguishable from placebo (Stier et al., Journal of Endocrinology and Metabolism)

GRAS Status

A company obtained a self-affirmed GRAS (Generally Recognized As Safe) opinion for AOD-9604 as a food ingredient; the US FDA has not made a GRAS determination and it is not in the FDA GRAS notice inventory. Important: GRAS does not mean therapeutic approval - it is exclusively a food-safety classification.

Cartilage-Repair Interest

AOD-9604 has been discussed in the context of cartilage-repair formulations, based on preclinical cartilage-regeneration data together with the trial safety profile. This is not a marketing authorisation as a medicine.

WADA Status

AOD-9604 is listed on the World Anti-Doping Agency (WADA) Prohibited List under the category "Peptide hormones, growth factors, related substances, and mimetics" (class S2). This is relevant for researchers working in sports medicine or exercise physiology contexts.

AOD-9604 vs. Full-Length hGH

Property	AOD-9604	hGH (full-length)
Structure	16 amino acids (C-terminal fragment)	191 amino acids
Lipolysis	Yes (via beta-3 receptors)	Yes
IGF-1 elevation	No	Yes
Insulin resistance	No	Yes (diabetogenic effect)
Tissue growth	No	Yes
Receptor dimerisation	No (binding site 2 absent)	Yes

Structure

AOD-9604: 16 amino acids (C-terminal fragment)
hGH (full-length): 191 amino acids

Lipolysis

AOD-9604: Yes (via beta-3 receptors)
hGH (full-length): Yes

IGF-1 elevation

AOD-9604: No
hGH (full-length): Yes

Insulin resistance

AOD-9604: No
hGH (full-length): Yes (diabetogenic effect)

Tissue growth

AOD-9604: No
hGH (full-length): Yes

Receptor dimerisation

AOD-9604: No (binding site 2 absent)
hGH (full-length): Yes

The key difference: AOD-9604 separates the lipolytic effect from the rest of hGH's actions. For research purposes, this is relevant because it allows investigation of fat metabolism pathways without the confounding effects of growth and glucose metabolism.

Cartilage Research

A lesser-known research field for AOD-9604 is cartilage regeneration. In a rabbit osteoarthritis model (collagenase-induced), intra-articular injection of AOD-9604 showed improved cartilage regeneration compared to untreated controls (Annu Clin Lab Sci, 2015).

The combination of AOD-9604 with hyaluronic acid (HA) produced better outcomes in this model than either substance alone. The authors suggest a synergistic effect: HA protects chondrocytes while AOD-9604 stimulates the production of proteoglycans and collagen in cartilage cells.

Mechanistically, the data suggest that AOD-9604 mimics developmental cascades that lead to the reformation of articular cartilage structures. Whether this effect translates to human joints is the subject of ongoing research.

Cartilage Research Status

Cartilage research on AOD-9604 is at the preclinical stage. Results are promising, but controlled human studies are lacking. AOD-9604 holds no TGA marketing authorisation as a medicine and is not on the Australian Register of Therapeutic Goods.

Quality and Sourcing

Purity Testing

For research-grade AOD-9604, check the batch-specific HPLC purity and MS identity on the current Certificate of Analysis (/coa) rather than relying on a fixed figure. At PeptidesDirect, each batch is independently tested by Janoshik Analytical.

A complete Certificate of Analysis (COA) for AOD-9604 must include: HPLC purity analysis, mass spectrometry for identity confirmation, peptide content, residual moisture, and counterion determination.

Storage

Store AOD-9604 as lyophilised powder at -20 °C. After reconstitution, keep refrigerated at 2-8 °C and use within 2-4 weeks.

EU Shipping: PeptidesDirect ships from within the EU. For deliveries within the EU, no customs or import fees, delivery in 2-3 working days with tracking.

Frequently Asked Questions

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Researchers sourcing AOD-9604 should look for independent purity testing, EU shipping, and transparent analytical data.