HPLC · CoA
What Is AOD-9604?
Explainer · 7 min read · Updated 30 September 2026
AOD-9604 is a laboratory-synthesised hexadecapeptide taken from the C-terminal region of human growth hormone, corresponding to residues 177 to 191 with a tyrosine added at the N-terminus. It was developed in Melbourne in the 1990s to isolate the region of the hormone associated with lipid metabolism in laboratory models, without the growth-promoting signalling of the intact protein. AOD-9604 is not a growth hormone, and it holds no medicine registration in any jurisdiction.
Macropus Peptides supplies AOD-9604 in 2mg and 5mg lyophilised vials for in-vitro research, with purity of 98% or higher on HPLC and a mass spectrum on file for every lot. The sections that follow describe the molecule, the studies that characterised it and its relationship to the closely related Frag 176-191.
What Is AOD-9604 Made Of?
AOD-9604 is made of 16 amino acids: a single tyrosine followed by the final fifteen residues (177 to 191) of the hormone. The parent hormone is a 191 residue chain folded into a four-helix bundle, with two cysteines near the C-terminus, at positions 182 and 189, joined by a disulfide bond. Research in the early 1990s asked whether that terminal segment carried an activity independent of the helices that bind the growth hormone receptor, and AOD-9604 was the stable synthetic analogue produced to test the question.
The name derives from its development code, Anti-Obesity Drug 9604. In the literature it is also written Tyr-hGH 177-191.
AOD-9604 Sequence and Structure
| Property | AOD-9604 |
|---|---|
| Sequence | Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe |
| One-letter code | YLRIVQCRSVEGSCGF |
| Length | 16 amino acids |
| Origin | Human growth hormone residues 177 to 191, plus an N-terminal tyrosine |
| Disulfide bond | Cys7 to Cys14, closing a small loop |
| Molecular weight | Approximately 1,815 daltons |
| Supplied form | White lyophilised powder |
The disulfide bridge is structurally significant. With the loop closed, the peptide adopts a compact conformation closer to that of the same segment within the intact hormone, and the published studies used this cyclised form.
What Is the AOD-9604 Mechanism of Action?
The AOD-9604 mechanism of action has not been fully defined, but adipocyte and rodent studies associated it with increased lipolysis and reduced lipogenesis through a pathway dependent on the beta-3 adrenergic receptor. Lipolysis is the hydrolysis of stored triglyceride; lipogenesis is the synthesis of new fatty acids from glucose. Work published in Endocrinology in 2001 compared obese mice with mice lacking the beta-3 adrenergic receptor and found that the lipid effects required that receptor, with beta-3 receptor expression in adipose tissue rising after exposure. A 2000 paper in Hormone Research examined its metabolic effects in rodent models.
The activities the fragment lacked are equally informative. In those models it did not raise IGF-1, did not alter insulin sensitivity in the manner of intact growth hormone, and did not stimulate the proliferation assays that respond to the full hormone. No dedicated receptor has been confirmed, so its precise molecular target remains an open research question.
Why the fragment leaves the growth hormone receptor inactive
Growth hormone activates its receptor by bridging two receptor molecules, which initiates JAK2 and STAT5 signalling. The binding surfaces responsible lie on the helices. A 16 residue segment of the C-terminus contains none of those surfaces and cannot dimerise the receptor, which is the structural basis for the absence of growth signalling in these studies.
Is AOD-9604 a Growth Hormone?
AOD-9604 is not a growth hormone; it is a derived fragment about one twelfth the length of the 191 residue parent, and published studies found it neither binds nor activates the growth hormone receptor. Laboratories studying the growth hormone axis itself use releasing hormone analogues and secretagogues that act on the pituitary, such as those in our growth hormone research peptide range.
How Does AOD-9604 Differ From Frag 176-191?
AOD-9604 differs from Frag 176-191 at a single position: AOD-9604 begins with an added tyrosine, while the native 176 to 191 fragment begins with phenylalanine. In human growth hormone, residue 176 is phenylalanine, so a true 176 to 191 fragment starts with that residue. AOD-9604 instead places a tyrosine in front of residues 177 to 191, and the remainder of the chain is identical.
| Feature | AOD-9604 | HGH Fragment 176-191 |
|---|---|---|
| First residue | Tyrosine | Phenylalanine in the native sequence |
| Residues 177 to 191 | Identical | Identical |
| Length | 16 | 16 |
| Prominence in the literature | Most later animal and clinical studies | Many early lipogenesis papers |
| Registered as a medicine | No | No |
The tyrosine was introduced during development and provides a residue suited to radiolabelling and detection. Some peptide sources label a tyrosine-containing sequence as 176-191, so the sequence stated on the certificate of analysis is the only reliable guide. We supply both, and the HGH Fragment 176-191 5mg vial allows a study to compare the native terminal segment directly with the modified one.
Comparing the two fragments in study design
Running the two fragments in parallel is one of few ways to ask whether a single residue substitution alters activity in an adipocyte assay. Both should come from lots with mass spectrometry identity data, so that any difference can be attributed to the peptide rather than to impurities.
What Is the Half-Life of AOD-9604?
The plasma half-life of AOD-9604 is not well characterised in peer-reviewed literature, and we have not found a pharmacokinetic figure we would cite with confidence. As a short linear peptide without an albumin-binding modification, it is expected to clear from plasma on a scale of minutes to hours rather than days. For laboratory purposes the more relevant figure is stability in the vial: sealed powder keeps best at -20 °C, and reconstituted stock is refrigerated for whatever in-use window the protocol sets.
Research History
- 1993: synthetic C-terminal growth hormone sequences examined for lipid effects in Biochemistry and Molecular Biology International
- 2000: metabolic studies of the modified fragment reported in Hormone Research
- 2001: obese and beta-3 receptor knockout mouse studies published in Endocrinology
- Mid 2000s: phase 2 and phase 2b clinical programmes, after which development for the original indication stopped
- 2013: a review of the clinical safety programme published in the Journal of Endocrinology and Metabolism
Each cited paper is collected in our AOD-9604 research library.
How Is AOD-9604 Prepared for Laboratory Work?
AOD-9604 is prepared by reconstituting the lyophilised powder in bacteriostatic water, or in dilute acetic acid where higher concentrations must remain fully in solution. A 5mg vial with 2 mL of diluent gives 2.5 mg per mL, which is 25 mcg per unit on a U-100 syringe. Laboratories setting up for the first time often choose the AOD-9604 starter kit, which pairs the 5mg vial with preserved diluent, syringes and swabs, while dilute acetic acid in 3 mL vials suits protocols that call for an acidic diluent.
Our recommendation: whichever fragment a study uses, confirm its sequence against the certificate of analysis before the first experiment. Before ordering, read how research peptides are regulated in Australia, since AOD-9604 is a Schedule 4 substance.
Questions about what is AOD-9604
Sources
- Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research. 2000.
Written by the Macropus Peptides technical team for in-vitro laboratory research reference. Not medical advice; products are not for human or veterinary use and are sold to buyers aged 18 and over.