AOD9604

Overview

AOD9604 is a synthetic analogue of the C-terminal region of human growth hormone, developed at Monash University in Australia and studied for effects on lipid metabolism. It progressed further into formal clinical investigation than the unmodified fragment it derives from.

It is not part of our catalogue. It is documented here because it is the compound behind much of the literature that gets cited on pages about hGH Fragment 176-191, and telling the two apart matters when reading that literature.

Chemical identity

• Also known as: AOD-9604, Tyr-hGH(177-191)
• CAS number: 221231-10-3
• Molecular formula: C₇₈H₁₂₃N₂₃O₂₃S₂
• Molecular weight: 1815.1 g/mol
• Classification: Growth hormone C-terminal fragment analogue
• PubChem CID: 71300630

At 1,815 g/mol it sits above the size where a structure diagram remains readable. The two sulfur atoms are cysteines forming a disulphide bridge, inherited from the parent hormone.

Not the same molecule as hGH Fragment 176-191

This distinction is worth making concrete, because it is almost never made:

• hGH Fragment 176-191: C₈₀H₁₂₇N₂₃O₂₄S₂ — 1859.1 g/mol. Residues 176 to 191 of growth hormone, unmodified.
• AOD9604: C₇₈H₁₂₃N₂₃O₂₃S₂ — 1815.1 g/mol. Residues 177 to 191, with a tyrosine attached at the front.

They differ by 44 g/mol and by two carbon atoms. One residue is dropped from the start of the sequence and a different one added in its place. That is a real chemical difference, easily resolved by mass spectrometry, and a supplier or a study that treats the names as interchangeable is being imprecise about which molecule is involved.

The practical consequence for reading the literature: most of the formal research — including the clinical work — used AOD9604, not the unmodified fragment. Citing it in support of claims about hGH Fragment 176-191 assumes an equivalence that has not been established.

The tyrosine, and why it is there

The added N-terminal tyrosine is the compound’s defining modification, and its origin is unusual: it was added for an experimental reason rather than a pharmacological one.

Tyrosine is the residue used to attach radioactive iodine to a peptide. Radioiodination is the standard method for tracking where a molecule goes in the body and how quickly it is cleared, and a peptide with no tyrosine cannot easily be labelled that way. The C-terminal region of growth hormone happens to contain none.

So a tyrosine was added at the N-terminus to make the peptide trackable — and it remained part of the molecule that went forward into development. AOD9604 carries a residue that exists because of how researchers needed to study it.

This is not unusual in drug development, but it is worth knowing, because it explains a modification that otherwise looks arbitrary and it is a reminder that a molecule’s structure records its history as well as its function.

Mechanism

The reported activity is the same as for the parent fragment: increased lipolysis and reduced lipogenesis in adipose tissue, without meaningful engagement of the growth hormone receptor and therefore without the IGF-1 and glucose effects that full-length growth hormone produces.

The mechanistic question is also the same, and equally unresolved. The beta-3 adrenergic receptor hypothesis has been examined directly using knockout models — the appropriate experiment — and the mechanism remains incompletely defined. The hGH Fragment 176-191 page covers this in more detail, along with the species caveat about beta-3 receptor prominence in rodents versus other species.

Research record

AOD9604 has the more developed record of the two, which is precisely why the distinction matters.

• Preclinical characterisation. Work from the Monash group examining metabolic effects in obese mouse models, including the beta-3 knockout experiments.
• Clinical investigation. The compound progressed into human trials for obesity, run by an Australian developer. Published results did not support continued development for that indication at the doses examined.
• Safety and tolerability. Human studies examining tolerability, which is the part of the record most often cited in secondary material.

That the clinical programme did not proceed is itself informative, and is generally omitted from summaries that cite the same compound’s earlier preclinical results approvingly.

Regulatory status

AOD9604 is not an approved medicine in any jurisdiction. Its clinical development for obesity did not result in a marketed product.

It appears on the World Anti-Doping Agency’s prohibited list, which is relevant to any research context involving competitive athletes.

Handling and storage

• Avoid reducing conditions. The disulphide bridge is structural; DTT, beta-mercaptoethanol or TCEP will open it.
• The added tyrosine is mildly photosensitive, more so than the unmodified fragment which contains no aromatic residue at that position.
• Lyophilised storage: sealed, refrigerated, protected from light; freeze for long-term storage.
• Reconstitution: add diluent slowly down the vial wall, allow to dissolve undisturbed, do not shake.

Purity and analytical verification

The identity question for this compound is the one described above, and it is unusually easy to answer.

AOD9604 and hGH Fragment 176-191 differ by 44 Da — 1815.1 against 1859.1. That is a large, unambiguous separation at this molecular weight, resolvable on any competent mass spectrometer. Given how routinely the two names are used interchangeably, asking which mass a certificate reports is a direct way to establish which molecule is in the vial.

The disulphide adds the same consideration as for the parent fragment: an intact bridge and a reduced open chain differ by two hydrogen atoms, detectable but only if someone is looking.

References

• 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
• 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 beta3-adrenergic receptor knock-out mice. Endocrinology, 2001. PMID 11713213

Summary

AOD9604 is a synthetic analogue of the C-terminal region of human growth hormone, CAS 221231-10-3, molecular formula C₇₈H₁₂₃N₂₃O₂₃S₂, molecular weight 1,815.1 g/mol — residues 177 to 191 with an N-terminal tyrosine added so the peptide could be radiolabelled and tracked. It is distinct from hGH Fragment 176-191, differing by 44 g/mol, and most of the formal research on this class was conducted with AOD9604 rather than the unmodified fragment. Its reported activity concerns lipid metabolism without growth hormone receptor engagement, its mechanism remains unresolved, and its clinical development for obesity did not result in an approved product. We do not stock it.

This page is provided for research reference. Compounds described in this library are for laboratory research use only, are not drugs, foods or cosmetics, and may not be used for any purpose other than in vitro or non-human laboratory research.