AOD-9604 Research, Specifications & Scientific Information

Introduction

AOD-9604 is a fragment. Human growth hormone is a 191-residue protein with several separable activities, and the premise behind this compound was that the part of the molecule associated with fat metabolism could be cut out and used on its own, leaving behind the parts that act through the growth hormone receptor. The result is a sixteen-residue peptide: the hormone's C-terminal fragment from residues 177 to 191, with a tyrosine added at the front ^[6].

The evidence base for that premise is old, small and almost entirely preclinical. The primary animal work was published between 2000 and 2001 by one research group ^{[1, 2, 3]}. A contemporaneous review records that the sponsor had phase IIa trials underway by February 2002 ^[4], but no report of a completed human trial is indexed in PubMed, and no study of the compound is registered on ClinicalTrials.gov. Most of what has been published about AOD-9604 since 2013 is anti-doping analytical chemistry.

This page is a reference record, and it states that evidence base as it is rather than as the compound's reputation would suggest. It describes research. It does not describe use in people or animals, and it carries no guidance of any kind on handling the material.

What Is AOD-9604?

AOD-9604 is a synthetic sixteen-residue peptide. The analytical literature defines it precisely: the C-terminal fragment of human growth hormone from amino acids 177 to 191, with an additional tyrosine residue at the N-terminus ^[6].

That definition resolves a naming confusion worth clearing up at the outset. The same material is widely listed as "hGH fragment 176-191". The fragment drawn from the hormone is residues 177 to 191; counting the added tyrosine as though it were residue 176 produces the other name. There is one compound, and two conventions for numbering it.

The compound originated in work at Monash University in Australia and was developed by the company Metabolic Pharmaceuticals, whose programme a 2004 review summarises in two sentences: the company was developing AOD-9604 for the potential treatment of obesity, and by February 2002 phase IIa trials were underway ^[4]. That review is the closest thing in the indexed literature to a record of the clinical programme.

AOD-9604 is not approved by the U.S. Food and Drug Administration for any indication. It is separately named in the anti-doping literature as a substance banned by the World Anti-Doping Agency ^[6].

AOD-9604 Specifications

AOD-9604 is described in the analytical literature as a peptide consisting of the C-terminal fragment of human growth hormone from amino acids 177 to 191, with an additional tyrosine residue added at the N-terminus. That is the reason two different names circulate for the same material: the fragment itself is hGH(177-191), and the added tyrosine makes the sixteen-residue molecule usually written as 'hGH fragment 176-191'. The two cysteine residues in the sequence correspond to the disulfide-bonded pair in the parent hormone, and the molecular formula carried by PubChem for compound identifier 71300630 includes both sulfur atoms; a single-letter string cannot show whether the bridge is formed, and identity work on supplied material has to establish it separately. Formula and mass agree between PubChem and the supplier catalog record. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does AOD-9604 Work?

The honest answer is that nobody has published a receptor for it.

That is not a gap this page can fill by analogy. The compound is derived from growth hormone, so the natural assumption is that it acts like growth hormone — and the published in vitro work is specifically constructed to rule that assumption out. In cells transfected with the human growth hormone receptor, the fragment neither competed for the receptor nor induced proliferation through it, while growth hormone itself did both ^[2].

What the rodent work describes instead is an effect on adipose tissue that appears without growth hormone receptor engagement: increased lipolytic activity and increased fat oxidation, alongside raised expression of the beta-3 adrenergic receptor, the principal lipolytic receptor of the fat cell ^{[1, 3]}. The authors' own conclusion is framed as a hypothesis about growth hormone rather than as a mechanism for the fragment: that growth hormone behaves as a pro-hormone, and that fragments of it can act through routes the intact hormone's own pathways do not describe ^[2].

A named pathway is therefore not available. What exists is a phenomenon in rodents and a negative result at the obvious receptor.

AOD-9604 Mechanism of Action

In vitro research

The in vitro component of the 2001 mouse study is the most load-bearing piece of mechanistic evidence published on this compound, and it is a negative one. Using BaF-BO3 cells transfected with the human growth hormone receptor, the authors measured radiolabelled growth hormone receptor binding and cell proliferation. AOD-9604 did not compete for the receptor, and it did not induce proliferation, whereas growth hormone did ^[2].

The second body of in vitro work is analytical rather than pharmacological. Incubation of AOD-9604 in serum and in urine produced six identifiable metabolites; quantification in serum identified one of them, a nine-residue fragment comprising the sequence CRSVEGSCG, as substantially more stable than either the other metabolites or the parent compound ^[6]. The practical consequence for a testing laboratory is that screening for the stable metabolite alongside the parent widens the detection window; the practical consequence for anyone characterising supplied material is that the parent peptide is not durable in biological matrices.

A separate study established that AOD-9604 does not influence the growth hormone isoform immunoassay used in anti-doping work ^[5] — a negative finding, and the reason a dedicated analytical method had to be built at all.

What Is AOD-9604 Being Researched For?

The published record divides into three parts, and they are of very different weight.

• Adipose and metabolic research in rodents — the original programme, published 2000–2001 in obese Zucker rats and in obese and non-obese mice ^{[1, 2, 3]}.
• Cartilage research in rabbits — a single 2015 study of intra-articular administration in a collagenase-induced knee osteoarthritis model ^[7].
• Anti-doping analytical chemistry — method development and metabolite identification, which is where most post-2013 publication on the compound sits ^{[5, 6]}.

The human record. There is no fourth part. A 2004 review records phase IIa trials underway in 2002 ^[4]; no peer-reviewed report of a completed human trial of AOD-9604 is indexed in PubMed, and a search of ClinicalTrials.gov returns no registered study of the compound. This page therefore carries no "Human Research" section, because there is no human research to describe. That absence is a finding about the compound, not an omission from the page.

Preclinical Research on AOD-9604

Animal research

Obese Zucker rats

Daily oral administration of 500 µg per kg of body mass for 19 days reduced body-mass gain by more than 50% relative to control — 15.8 ± 0.6 g against 35.6 ± 0.8 g. Adipose tissue from treated animals showed increased lipolytic activity. In contrast to chronic administration of intact growth hormone, chronic administration of the fragment showed no adverse effect on insulin sensitivity as measured by euglycaemic clamp ^[1].

That insulin-sensitivity comparison is the point of the study. It is what the whole fragment premise rests on: growth hormone's effect on fat comes packaged with a diabetogenic effect on glucose handling, and the claim is that the fragment separates the two.

Obese and non-obese mice

Obese ob/ob mice and non-obese C57BL/6J mice received growth hormone, AOD-9604 or saline for 14 days by mini-osmotic pump. Both growth hormone and the fragment significantly reduced body-mass gain in the obese animals, with increased in vivo fat oxidation and increased plasma glycerol, an index of lipolysis. Unlike growth hormone, AOD-9604 did not induce hyperglycaemia and did not reduce insulin secretion ^[2].

Beta-3 adrenergic receptor experiments

A companion study looked for the receptor route. After 14 days of chronic intraperitoneal administration in obese mice, both growth hormone and the fragment reduced body mass and adiposity, and both raised the expression of beta-3 adrenergic receptor RNA — which is repressed in obese mice — to levels comparable with non-obese animals ^[3].

The knockout experiment is what makes this informative. In beta-3 adrenergic receptor knockout mice, long-term administration of either compound failed to produce the body-mass change and the lipolysis seen in wild-type controls. But in an acute experiment, AOD-9604 still raised whole-body metabolic rate and fat oxidation in those same knockout animals. The authors' conclusion is that the lipolytic actions are not mediated directly through the beta-3 adrenergic receptor, even though both compounds increase its expression ^[3].

Rabbit knee osteoarthritis model

Thirty-two mature New Zealand white rabbits received collagenase type II in each knee joint, then weekly intra-articular injections of saline, hyaluronic acid, AOD-9604, or AOD-9604 with hyaluronic acid, for four to seven weeks. Gross morphological and histopathological scores were significantly worse in the saline group than in the other three, and significantly better in the combination group than in either single-agent group. The period of lameness in the combination group was significantly shorter than in the other three groups ^[7].

This is one study, in one model, in one laboratory, with an endpoint scored by observers, and it sits in a different research area from everything above it.

Findings described in this section were observed in animals. Rodent models of obesity and collagenase-induced joint models in rabbits are standard preclinical tools, and nothing in them establishes anything about humans.

Other Areas of AOD-9604 Research

In vitro research

Publication on AOD-9604 did not stop in 2001; it changed discipline. Since 2013 the compound has appeared mainly in the anti-doping analytical literature, because it is prohibited in sport and had to be made detectable ^[6].

That work produced two things of interest to anyone characterising the material. First, a validated solid-phase extraction method in urine with a limit of detection of 50 pg/mL, reported with good linearity, precision below 20%, specificity and 62% recovery ^[6]. Second, the metabolite map described in the mechanism section above, which tells a laboratory what the parent peptide turns into in a biological matrix.

The same body of work records something about the compound's availability that is relevant context rather than pharmacology: the peptide has been offered on internet websites and was identified in confiscated vials in the United States ^[6]. That is a statement about circulation, not about any property of research-grade material supplied under a certificate of analysis.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

AOD-9604 vs Related Compounds

The comparison worth drawing is with the hormone AOD-9604 derives from, and with the compounds that act on the same axis by a different route.

Against growth hormone itself

AOD-9604 is a sixteen-residue fragment of the 191-residue hormone. The published in vitro work reports that it does not bind the growth hormone receptor and does not drive proliferation through it ^[2]. It is therefore not a growth hormone analogue in the pharmacological sense, whatever its origin.

Against secretagogues

Tesamorelin, CJC-1295 and ipamorelin act upstream, on the release of endogenous growth hormone from the pituitary. AOD-9604 does not act on that axis at all; it is a fragment administered directly.

Evidence weight

This is the material difference. The compounds above have human pharmacokinetic and pharmacodynamic data in the indexed literature. AOD-9604 does not.

Regulatory position

AOD-9604 is not approved for any indication in the United States and is prohibited in sport ^[6].

No comparison of effect between these compounds is made on this page. Where comparative data exist they belong to the papers that report them, and for this compound they largely do not exist.

Chemical & Molecular Characteristics

AOD-9604 is a sixteen-residue peptide. The published sequence is YLRIVQCRSVEGSCGF, corresponding to human growth hormone residues 177 to 191 with an N-terminal tyrosine ^[6].

Three points qualify that string.

The disulfide is not visible in it. The two cysteine residues correspond to the disulfide-bonded pair in the parent hormone, and the molecular formula recorded by PubChem for compound identifier 71300630 carries both sulfur atoms. Single-letter code cannot show whether a bridge is formed, so identity work on supplied material has to establish the oxidation state separately rather than infer it from the sequence.

The stable metabolite is a subsequence. The nine-residue fragment CRSVEGSCG identified as the persistent species after incubation in serum ^[6] sits inside the sequence above and spans both cysteines. That is worth knowing when interpreting a chromatogram of degraded material: the degradation product is not a random cut.

The identifiers agree. CAS registry number 221231-10-3 validates against the CAS check-digit algorithm; UNII 7UP768IP4M and PubChem compound identifier 71300630 both resolve for this compound, and the formula C78H123N23O23S2 with a mass of approximately 1815.1 g/mol matches the value carried in the supplier catalog for the material offered as a laboratory reagent.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Ng FM, Sun J, Sharma L, et al.. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone Hormone research; 2000. PMID 11146367 doi:10.1159/000053183
2. Heffernan MA, Thorburn AW, Fam B, et al.. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity; 2001. PMID 11673763 doi:10.1038/sj.ijo.0801740
3. Heffernan M, Summers RJ, Thorburn A, et al.. 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 Endocrinology; 2001. PMID 11713213 doi:10.1210/endo.142.12.8522
4. Wilding J. AOD-9604 Metabolic Current opinion in investigational drugs (London, England : 2000); 2004. PMID 15134286
5. Orlovius AK, Thomas A, Schänzer W, et al.. AOD-9604 does not influence the WADA hGH isoform immunoassay Drug testing and analysis; 2013. PMID 24124033 doi:10.1002/dta.1557
6. Cox HD, Smeal SJ, Hughes CM, et al.. Detection and in vitro metabolism of AOD9604 Drug testing and analysis; 2015. PMID 25208511 doi:10.1002/dta.1715
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. PMID 26275694

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: AOD-9604 specifications and lot documentation