AOD-9604 is the carboxy-terminal sixteen residue fragment of human growth hormone, sold and cited under two names that describe one sequence. It carries the two cysteines that form the C-terminal disulfide loop of the parent hormone and none of the residues that contact the growth hormone receptor. Work on the fragment centres on whether the lipolytic activity ascribed to intact growth hormone survives truncation to this short peptide.
Key facts
| Type | Carboxy-terminal fragment of human growth hormone |
| Amino acid count | 16 |
| Sequence | Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe |
| Molecular formula | C78H123N23O23S2 |
| Molecular weight | 1815.1 g/mol oxidised, 1817.1 g/mol reduced |
| CAS number | 221231-10-3 |
| Disulfide bond | Cys7 to Cys14, forming a twelve membered loop |
| Synonyms | HGH fragment 176-191, hGH 177-191 with N-terminal tyrosine, AOD9604 |
Structure and chemistry
Human growth hormone is a 191 residue four helix bundle held by two disulfide bonds. The second of those, between Cys182 and Cys189, closes a small loop near the C-terminus. AOD-9604 reproduces that loop and the residues flanking it. Counting from the parent numbering the fragment spans positions 176 to 191, which is where the alternative name comes from. The tyrosine at the N-terminus corresponds to Tyr176, so the two names describe an identical primary sequence and the distinction between them is one of nomenclature and manufacturing origin.
The disulfide accounts for a discrepancy that appears across supplier documentation. With Cys7 and Cys14 oxidised into the loop the calculated average mass is 1815.1 g/mol. With those cysteines reduced and carrying free thiols the mass rises by two hydrogens to 1817.1 g/mol. Both figures circulate as the molecular weight of the fragment. Certificates that quote 1817 without stating redox state describe the linear peptide; the cyclic form is what mass spectrometry of correctly folded material returns.
Solid phase synthesis of the linear chain is straightforward at sixteen residues. The controlled step is oxidation, usually run dilute in mildly basic aqueous buffer so that the intramolecular bond forms in preference to intermolecular dimers. Analytical separation of the cyclic monomer from the reduced peptide and from disulfide-linked dimers is what reversed phase HPLC on this compound is measuring, and a purity figure quoted without a note on redox state carries little information.
Mechanism of action
Intact growth hormone acts through a single-pass cytokine receptor that dimerises on binding and signals through JAK2 and STAT5. The residues that make those receptor contacts sit in helices one and four of the bundle and are absent from the fragment, so AOD-9604 does not engage the growth hormone receptor and produces no STAT5 phosphorylation in reporter assays. Growth hormone driven IGF-1 transcription in hepatocyte culture is likewise unaffected.
The activity attributed to the fragment is a separate lipolytic effect, first described in adipose tissue explants and later in isolated adipocytes. Reported readings include reduced lipogenic enzyme expression and increased beta-3 adrenergic receptor transcript. No high affinity receptor has been isolated for the peptide, and proposed models place the effect on beta-3 adrenergic signalling and on mitochondrial oxidative capacity in adipocytes without a defined binding partner. Results across laboratories have not been consistent, and the compound is used in cell work as much to probe that inconsistency as to exploit the effect.
Research applications
- Adipocyte culture: lipolysis measured as glycerol or free fatty acid release into medium, against isoproterenol as the beta-adrenergic comparator.
- Beta-3 adrenergic receptor transcript and protein quantification in 3T3-L1 and primary adipocytes after fragment exposure.
- Growth hormone receptor selectivity screens: STAT5 reporter and IGF-1 transcription assays run to confirm the absence of somatotropic signalling.
- Redox characterisation: reversed phase HPLC and LC-MS separation of the cyclic monomer, the reduced linear peptide and disulfide dimers.
- Serum and plasma stability work tracking loop opening and proteolytic clipping of the exposed N-terminal tyrosine.
- Comparative fragment mapping against other growth hormone derived sequences to localise the lipolytic determinant.
Compounds studied around energy balance and adipocyte biology sit in NuVion’s Metabolism category.
Handling in the laboratory
Short disulfide-bridged peptides are supplied lyophilised and reconstituted with bacteriostatic water run slowly down the wall of the vial, then swirled. Shaking drives foaming at the air interface, which promotes both aggregation and thiol exchange. The reconstitution calculator converts vial content and diluent volume into a stock concentration.
Reducing agents in buffers are the main handling hazard for this sequence. Dithiothreitol, tris(2-carboxyethyl)phosphine and high concentrations of free cysteine will open the loop and convert cyclic material to the linear peptide, changing the mass by two units and, on the available evidence, the activity. Reconstituted stock is held cold, protected from light and aliquoted so that the vial is opened once. Repeated freeze and thaw cycles on a cysteine-containing peptide are a common source of drifting assay results.
Testing and supply from NuVion
NuVion supplies a tested range across the growth hormone axis, including HGH, CJC-1295 No DAC, Ipamorelin, Sermorelin and Tesamorelin. That range is manufactured at a GMP-audited facility and independently tested by Janoshik Analytical, with purity determined by RP-HPLC and identity confirmed by mass spectrometry, and the certificates are published in the Certificate of Analysis library. AOD-9604 is not part of the current catalogue and this page is a reference profile.
Related compounds
The parent molecule is covered in the HGH profile. Compounds that raise endogenous growth hormone release instead of fragmenting the hormone include CJC-1295 and sermorelin at the GHRH receptor, ipamorelin, GHRP-2 and GHRP-6 at the ghrelin receptor, and the orally active secretagogue MK-677. Downstream of the axis, IGF-1 LR3 covers the mediator arm.
Frequently asked questions
Is AOD-9604 the same as HGH fragment 176-191?
The primary sequence is the same sixteen residues, so in practice the two names describe one peptide. AOD-9604 is the designation from the Australian development programme that took the fragment forward and specifies the cyclic, disulfide-bridged form; HGH fragment 176-191 is the descriptive name drawn from the parent hormone numbering and is used loosely for either the cyclic or the reduced peptide. Certificates that state the redox state are the ones worth reading.
Why do sources quote two different molecular weights?
The cyclic peptide with the Cys7 to Cys14 bond formed has an average mass of 1815.1 g/mol. Opening that bond adds two hydrogen atoms and gives 1817.1 g/mol. Both numbers are correct for their respective forms, and a supplier document quoting one without naming the other is describing a single redox state.
Does the fragment act on the growth hormone receptor?
It does not. The receptor binding surface of growth hormone is built from residues in helices one and four, none of which are present in a sixteen residue C-terminal fragment. Reporter assays confirm the absence of STAT5 signalling, which is the point of the molecule as a research tool: it separates the lipolytic observation from somatotropic signalling.
Is AOD-9604 listed in the Australian Register of Therapeutic Goods?
No. AOD-9604 is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. Material of this class is supplied in Australia as a laboratory chemical for in vitro research.
Research use only. The compound described on this page is discussed as a laboratory chemical used in in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.
