AOD9604 vs Fragment 176-191: What Is the Difference?

Research peptide catalogues often list two names side by side: AOD9604 and HGH Fragment 176-191. Both are derived from the last amino acids of human growth hormone (hGH), and both appear in adipose tissue research. Yet they differ in one amino acid, in the amount of available data, and in how clearly it is defined what is actually sold under each name.

Below you will find a comparison of the origin, structure, research data and regulatory status of the two molecules. The final part explains how a certificate of analysis tells you which of them a sample contains.

Where the two compounds come from

Human growth hormone is a protein of 191 amino acids. It affects tissue growth, glucose levels, IGF-1 production and fat metabolism. In the 1990s, Frank Ng's group at Monash University in Melbourne investigated whether the effect on adipose tissue could be traced to a small part of the molecule.

In 1993, Wu and Ng reported that a synthetic peptide matching the hGH 177–191 region (15 amino acids) suppressed fat synthesis in rat adipose tissue in a similar way to the whole hormone. A year later, the same group reported that long-term administration of this peptide to obese mice reduced weight gain and adipose tissue mass.

A stabilised version followed. A tyrosine was added to the start of the 177–191 chain (the N-terminus). The result was a 16-amino-acid peptide, Tyr-hGH 177–191, known as AOD9604. According to published work, the tyrosine stabilises the peptide. AOD9604 was developed further by the Australian company Metabolic Pharmaceuticals.

The name “Fragment 176-191”, on the other hand, refers to the natural end of hGH, i.e. amino acids 176 to 191. The natural sequence starts with phenylalanine, not tyrosine. That is the core of the whole comparison.

Structure side by side

Both molecules have 16 amino acids. They share the same 15 amino acids of the 177–191 region, including the disulfide bridge between two cysteines that closes part of the chain into a ring. They differ only in the first amino acid.

Tyrosine differs from phenylalanine by a single hydroxyl group (–OH) on the aromatic ring. In the formula that is one extra oxygen atom, and in molecular weight roughly 16 g/mol. Chemically it is a small change, but analytically it can be distinguished reliably. Data for AOD9604 come from PubChem and the FDA evaluation; values for the 176–191 sequence are calculated from the hGH sequence in the UniProt database.

Mechanism as described in research

Most mechanistic data come from animal studies and concern AOD9604 or the 177–191 peptide. Ng et al. (2000) gave AOD9604 orally to obese Zucker rats for 19 days. Weight gain was roughly half that of the control group, and adipose tissue showed higher lipolytic activity, meaning faster breakdown of stored fat. Unlike whole hGH, insulin sensitivity in the animals did not worsen.

Heffernan et al. (2001) followed obese mice after 14 days of treatment with hGH or AOD9604. Both reduced body weight and fat mass and increased the expression of beta-3 adrenergic receptors (β3-AR) in adipose tissue. In mice lacking the β3-AR gene, chronic treatment produced neither weight loss nor increased lipolysis. The authors concluded that the effect is not mediated directly through β3-AR, but that the increased receptor expression may contribute to it. The FDA's 2024 evaluation summarises that the specific molecular target of AOD9604 remains unknown.

According to the review by Stier et al. (2013) and the FDA evaluation, AOD9604 did not displace hGH from its receptor in cell assays and did not stimulate proliferation of cells carrying that receptor. This is consistent with later clinical findings in which AOD9604 did not affect IGF-1 levels.

For the native 176–191 sequence starting with phenylalanine, we found no separate published studies. The data commonly cited for the “fragment” relate to the 177–191 peptide or to AOD9604.

Clinical development of AOD9604

Between 2001 and 2006, six randomised, double-blind, placebo-controlled trials with a total of 893 participants were conducted with AOD9604 (Stier et al., 2013). All were funded by Metabolic Pharmaceuticals.

A 12-week phase II study in 300 obese adults (Herd, Wittert et al., 2005) was published only as a conference abstract. The authors reported a somewhat greater weight decrease than with placebo and a non-linear dose–response relationship. In 2024 the FDA noted that the full results of this study were never published.

The decisive study was the phase IIb trial called OPTIONS. It included 536 obese adults, lasted 24 weeks, and all participants, including the placebo group, followed a diet and exercise programme. On 21 February 2007 the company announced that the difference from placebo did not reach statistical significance at either 12 or 24 weeks. It terminated the development of AOD9604 for the treatment of obesity.

The safety summary of all six trials (Stier et al., 2013) reports adverse events at placebo level, no change in IGF-1 levels and no antibodies against AOD9604. The authors were linked to Metabolic Pharmaceuticals, as they state in their declaration of interests. In its 2024 evaluation, the FDA pointed to the limited amount of published data and to possible immunogenicity, i.e. the ability of the peptide to trigger an immune response.

In the same 2007 announcement, the company said it would continue to investigate AOD9604 in the field of osteoporosis. The published literature includes, for example, a study in a rabbit model of osteoarthritis in which the compound was administered into the knee joint (Kwon and Park, 2015). This is preclinical research.

Regulatory and sport status

Neither AOD9604 nor Fragment 176-191 is authorised as a medicinal product. In April 2013, WADA stated that AOD9604 had not been approved for therapeutic use by any government health authority in the world. In its November 2024 evaluation, the FDA noted that there is no approved product containing AOD9604 in the USA. It also proposed not to include the substance (neither the free base nor the acetate) on the list of substances that US pharmacies may use for individual compounding (the 503A Bulks List). As reasons it cited a lack of evidence of effectiveness and possible safety risks, including immunogenicity.

In sport, both compounds are prohibited. In 2013, WADA placed AOD-9604 in category S0, the non-approved substances. The current WADA Prohibited List, in force from 1 January 2026, lists growth hormone fragments in category S2.2.3 and explicitly names “AOD-9604 and hGH 176-191” as examples. Substances in category S2 are prohibited at all times, in and out of competition.

Timeline

Why the names get mixed up and how to tell what is in a sample

The confusion has several causes. In the scientific literature, AOD9604 is described as the “lipolytic fragment of hGH”, even though it is a modified sequence. On the market, different molecules are then sold under the name “HGH Fragment 176-191”. Sometimes it is the native sequence starting with phenylalanine, but often it is the tyrosine variant, which is identical in sequence to AOD9604. Identifiers are unclear too: in 2024 the FDA pointed out that some suppliers give a different CAS number for AOD9604 (386264-39-7) and that the structure shown on their websites does not always match the sequence.

The name on the label is therefore not enough. What matters is the certificate of analysis (CoA) and two different types of data in it:

• HPLC (high-performance liquid chromatography) shows purity, i.e. what proportion of the sample is the main component. It does not, however, tell you which molecule it is.
• MS (mass spectrometry) measures the mass of the molecule. That mass can be compared with the theoretical value for a given sequence.

For these two compounds the comparison is straightforward. The theoretical monoisotopic mass of AOD9604 is approximately 1813.9 Da; for the native 176–191 sequence it is approximately 1797.9 Da. Mass spectrometry reliably resolves a 16 Da difference. Peptides often appear in the spectrum as multiply charged ions. The doubly protonated ion [M+2H]²⁺ falls at around m/z 908 for AOD9604 and around m/z 900 for the 176–191 sequence. If the measured mass matches AOD9604, the sample contains the tyrosine variant, whatever the label says.

Certificates of analysis (HPLC) for Arion Bios batches are available on the certificates of analysis page. You can match a certificate to a specific package by the production date printed on it.

What Arion Peptides offers

Both compounds are available as lyophilised powder in vials: AOD9604 5 mg and Fragment 176-191. They are intended exclusively for laboratory and research purposes. A more detailed overview of the studies associated with the fragment can be found in the article Fragment 176-191: Mechanism of Action and Study Overview.

Frequently Asked Questions

Is AOD9604 the same as Fragment 176-191?

Not quite. AOD9604 is the hGH 177–191 region with an added tyrosine at the start. The native 176–191 region starts with phenylalanine. Both molecules have 16 amino acids and differ only in the first one. However, some products sold as Fragment 176-191 contain a sequence identical to AOD9604.

Why do the clinical trials concern only AOD9604?

The clinical programme was run by Metabolic Pharmaceuticals, which tested its own stabilised molecule, AOD9604. No separate human studies of Fragment 176-191 have been published. Results of AOD9604 studies therefore cannot automatically be applied to a different sequence.

Are both compounds prohibited in sport?

Yes. The WADA Prohibited List for 2026 names both AOD-9604 and hGH 176-191 among growth hormone fragments in category S2. The ban applies at all times.

How can I tell which molecule a sample contains?

From the mass spectrometry data in the certificate of analysis. A measured mass of around 1815 g/mol corresponds to the AOD9604 sequence; a value of around 1799 g/mol corresponds to the native 176–191 sequence. HPLC purity alone does not confirm identity.

Is either compound approved as a medicine?

No. Neither is authorised as a medicinal product. Development of AOD9604 for the treatment of obesity was terminated in 2007.

Sources

1. Wu Z, Ng FM, “Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone”, Biochemistry and Molecular Biology International, 1993;30(1):187–196: pubmed.ncbi.nlm.nih.gov
2. Natera SH, Jiang WJ, Ng FM, “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, 1994;33(5):1011–1021: pubmed.ncbi.nlm.nih.gov
3. Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R, “Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone”, Hormone Research, 2000;53(6):274–278. DOI: 10.1159/000053183
4. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM, “The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and β3-AR knock-out mice”, Endocrinology, 2001;142(12):5182–5189. DOI: 10.1210/endo.142.12.8522
5. Stier H, Vos E, Kenley D, “Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans”, Journal of Endocrinology and Metabolism, 2013;3(1-2):7–15. DOI: 10.4021/jem157w
6. Metabolic Pharmaceuticals Limited, “Metabolic's obesity drug – Phase 2B clinical trial results”, announcement to the Australian Securities Exchange (ASX), 21 February 2007 (SEC archive): sec.gov
7. Kwon DR, Park GY, “Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model”, Annals of Clinical and Laboratory Science, 2015;45(4):426–432: pubmed.ncbi.nlm.nih.gov
8. U.S. Food and Drug Administration, “FDA Evaluation of AOD-9604-Related Bulk Drug Substances”, briefing material for the Pharmacy Compounding Advisory Committee, 2024 (also summarises the Herd, Wittert et al. 2005 abstract): fda.gov
9. WADA, “WADA Statement on substance AOD-9604”, 24 April 2013 (reprinted by the International Weightlifting Federation): iwf.sport
10. WADA, “The 2026 Prohibited List”, category S2.2.3, in force from 1 January 2026: wada-ama.org
11. UniProt, “P01241 – Somatotropin (GH1), Homo sapiens”, human growth hormone sequence: uniprot.org
12. PubChem, “AOD-9604, CID 71300630”, molecular formula and molecular weight: pubchem.ncbi.nlm.nih.gov