AOD-9604: Research Compound Overview

AOD-9604 is a 16-residue peptide with the sequence YLRIVQCRSVEGSCGF (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe) and an intramolecular disulfide bond between Cys7 and Cys14.

• CAS number: 221231-10-3
• Molecular formula: C78H123N23O23S2
• Molecular weight: approximately 1815.1 g/mol
• Length: 16 amino acids, cyclic (7→14) disulfide
• Registry identifiers: DrugBank DB06388; FDA UNII 7UP768IP4M (also listed as LAT-8881)

Residues 2–16 correspond to amino acids 177–191 of human growth hormone, the C-terminal segment that earlier work had associated with effects on adipocyte lipid metabolism. The N-terminal tyrosine was added to the native fragment, giving the peptide an aromatic residue useful for UV detection and labelling. The disulfide-constrained loop mirrors the Cys182–Cys189 bridge of intact hGH. The sequence carries two arginine residues and one glutamate, giving a net positive charge at neutral pH. Research material is produced by solid-phase peptide synthesis followed by oxidative disulfide formation.

Preclinical work on AOD-9604 has examined how a growth hormone fragment can interact with lipid metabolism without the broader signalling of the full hormone.

Receptor binding and proliferation. Heffernan et al. (International Journal of Obesity, 2001) compared AOD-9604 with intact hGH in obese and lean mouse strains and in BaF-BO3 cells expressing the hGH receptor. Unlike hGH, AOD-9604 did not bind the hGH receptor or stimulate cell proliferation in that assay, and it did not alter blood glucose or insulin in the animal studies.

Beta-3 adrenergic receptor involvement. In a companion study, Heffernan et al. (Endocrinology, 2001) examined lipid metabolism and beta-3 adrenergic receptor (β3-AR) mRNA in obese mice and in β3-AR knockout mice. The authors concluded that the lipolytic activity of the fragment was not directly mediated through β3-AR, although changes in receptor expression were observed in obese wild-type animals.

Insulin sensitivity. A study in Hormone Research (2000) used euglycemic clamp techniques in obese Zucker rats and reported increased adipose tissue lipolytic activity without the impairment of insulin sensitivity associated with chronic exposure to intact hGH.

Metabolic fate. Cox et al. (Drug Testing and Analysis, 2015) incubated AOD-9604 in serum and urine, identified six candidate metabolites, and found that one was considerably more stable than the parent peptide.

Published research on AOD-9604 is concentrated in the following areas:

• Endocrinology and metabolism: adipocyte lipolysis, lipogenesis and energy expenditure in rodent models, and the dissociation of these activities from hGH receptor signalling.
• Growth hormone structure–function research: mapping which regions of hGH carry particular biological activities.
• Receptor pharmacology: the role of β3-adrenergic receptors in fragment-associated lipid metabolism.
• Analytical and anti-doping chemistry: extraction and detection methods in urine, metabolite identification, and stability of degradation products.

AOD-9604 has been investigated in clinical research and is not an approved drug. It is referenced in the anti-doping analytical literature as a prohibited peptide. CheatCodes supplies it strictly as a research-use-only reference material for laboratory investigation and not for any other purpose.

Because the fragment differs from intact hGH in receptor binding, well-characterized material and explicit reporting of disulfide status are important when comparing studies.

AOD-9604 is supplied as a lyophilized (freeze-dried) powder. In the dry state, disulfide-containing peptides are generally most stable when kept at -20 °C or below, sealed, desiccated and protected from light. Vials should be allowed to reach room temperature before opening so that atmospheric moisture does not condense on the powder.

The Cys7–Cys14 disulfide is central to the peptide's defined structure. Reducing agents such as dithiothreitol, β-mercaptoethanol or TCEP will open the bond and should be excluded from stock solutions unless reduction is intended. At alkaline pH, disulfides can also undergo exchange or scrambling, so mildly acidic to neutral conditions are generally preferred for storage of solutions. The glutamine residue is a potential site of slow deamidation in solution over extended periods.

The peptide contains several hydrophobic residues (Leu, Ile, Val, Phe) alongside its charged residues; it is generally soluble in water or dilute acidic aqueous solution, and gentle mixing is preferred over vigorous agitation to reduce aggregation. Common laboratory practice is to prepare a concentrated stock in a suitable sterile solvent, divide it into single-use aliquots, and store the aliquots frozen to avoid repeated freeze–thaw exposure.

The N-terminal tyrosine provides measurable absorbance at 280 nm, which can support concentration checks, although net peptide content from the COA remains the most direct reference. Glass or low-binding polypropylene vials help reduce adsorptive losses at low concentrations.

Every CheatCodes lot of AOD-9604 is analyzed by reverse-phase HPLC for chromatographic purity and by mass spectrometry for identity confirmation, with the observed mass compared against the theoretical value for the expected sequence. The findings of that analysis are recorded on a lot-specific certificate of analysis (COA), which is published in the CheatCodes COA library and can be matched to the lot number printed on each vial.

Lot traceability matters for reproducibility. Synthetic peptides can differ between batches in purity, counter-ion content (for example acetate or trifluoroacetate), water content and the profile of minor related impurities such as deletion or truncated sequences. For a disulfide-bonded peptide such as AOD-9604, the observed mass also confirms the oxidized (cyclized) form, which is 2 Da lighter than the reduced linear peptide. Recording the lot number alongside experimental data allows a laboratory to compare runs across material batches, to investigate unexpected variation, and to report the analytical characterization of the material in methods sections. Researchers are encouraged to retain the COA with their laboratory records and to use net peptide content, rather than gross powder weight, when preparing stock solutions.

A certificate of analysis for a synthetic peptide generally identifies the compound name, lot number and test date, reports HPLC purity as a percentage of total peak area, and records the mass observed by MS against the expected value. Reviewing these fields before an experiment confirms that the material on the bench matches the material described in the laboratory record.