AOD-9604 5mg

What is AOD-9604 ?

AOD-9604 is a modified fragment of human growth hormone: residues 177-191 with a tyrosine added at the N-terminus. Research has examined lipolysis and fatty-acid oxidation in animal models, without the growth-promoting and insulin-resistance effects of intact growth hormone.

The sequence is Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (YLRIVQCRSVEGSCGF). The literature writes it as Tyr-hGH(177-191), AOD9604 or AOD 9604. Its molecular weight is 1815.12 g/mol and its CAS number 221231-10-3. The cysteines at positions 7 and 14 form an intrachain disulfide, matching Cys182 and Cys189 of the parent hormone.

Each AOD-9604 5mg vial holds white lyophilised powder.

AOD-9604 Research Applications

• Lipolysis in obese rats : Ng and colleagues (Horm Res, 2000) reported higher lipolytic activity in adipose tissue of obese Zucker rats given oral AOD9604. Body-weight gain was less than half that of controls, and insulin sensitivity did not change.
• Beta-3 adrenergic receptors : in obese mice, 14 days of treatment reduced body weight and fat and restored beta-3 receptor RNA to lean levels. In beta-3 receptor knock-out mice chronic treatment had no such effect (Heffernan et al., Endocrinology, 2001).
• Structure : Ogru and colleagues (J Pept Res, 2000) found type I beta-turns in the disulfide-bridged fragment by NMR, and lipolytic activity in rodent, porcine and human adipose tissue in vitro.
• Human trials : six randomised, double-blind, placebo-controlled trials reported no change in serum IGF-1 and no negative effect on carbohydrate metabolism (Stier, Vos and Kenley, J Endocrinol Metab, 2013).

Typical designs are lipolysis and fatty-acid oxidation assays in adipocytes and rodent models, and comparisons of intact hGH with its C-terminal fragments. A related fragment, AOD-9401, raised lipolysis and reduced lipogenesis in isolated human adipose tissue in vitro (Heffernan et al., Am J Physiol Endocrinol Metab, 2000). Efficacy in obesity was never established in humans. AOD-9604 has no marketing authorisation as a medicine.

AOD-9604 vs hGH Fragment 177-191

hGH Fragment 177-191 is the 15-residue chain Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe. AOD-9604 is the same chain with a tyrosine added at the N-terminus, giving 16 residues and 1815.12 g/mol. Both carry the disulfide loop of the hGH C-terminus. Ogru and colleagues (J Pept Res, 2000) did their NMR work on the 15-residue form, where the cysteines sit at positions 6 and 13. The main metabolic studies and the human trials used AOD-9604 itself (Ng et al., 2000; Heffernan et al., 2001; Stier et al., 2013). Because residue 176 of hGH is a tyrosine, AOD-9604 has the same sequence as HGH Fragment 176-191, which we also stock. Head-to-head data are scarce, so the added tyrosine is the variable under test.

Research Overview

AOD-9604 is a synthetic 16-residue peptide corresponding to the C-terminal fragment of human growth hormone, residues 177-191, with an additional tyrosine residue at the N-terminus: sequence Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (YLRIVQCRSVEGSCGF), molecular formula C₇₈H₁₂₃N₂₃O₂₃S₂, molecular weight 1815.12 g/mol, CAS 221231-10-3. The two cysteine residues at positions 6 and 14 form an intrachain disulfide bridge that holds the fragment in the looped C-terminal conformation of the native hormone; that bridged structure was characterised by NMR in the original conformational analysis by Ogru and colleagues (J Pept Res, 2000). The compound is written Tyr-hGH(177-191) throughout much of the literature.

AOD-9604 was designed and developed by Metabolic Pharmaceuticals (Melbourne, Australia) as an anti-obesity candidate. The design goal was to isolate the lipid-mobilising activity of human growth hormone from its growth-promoting and insulin-resistance effects, which limit the use of the intact 191-residue hormone. Because AOD-9604 contains only the C-terminal domain, it lacks the second receptor binding site that full-length hGH requires to dimerise its receptor and initiate growth signalling. Development progressed through phase I and phase 2b clinical studies in obesity, six randomised, double-blind, placebo-controlled trials summarised by Stier, Vos and Kenley (J Endocrinol Metab, 2013), before the company's development programme was wound down.

The published preclinical work centres on lipid metabolism. Ng and colleagues (Horm Res, 2000) reported increased lipolytic activity in the adipose tissue of obese Zucker rats treated with AOD9604. Heffernan and colleagues (Am J Physiol Endocrinol Metab, 2000) reported that oral administration of the fragment altered lipid metabolism in rodents, and the group's follow-up study in obese mice and β3-adrenergic receptor knock-out mice (Endocrinology, 2001) reported that chronic treatment reduced body weight and body fat, restored β3-adrenergic receptor expression, and did so without raising IGF-1 or impairing glucose handling, the two effects that make intact hGH unsuitable for this indication. The clinical summary is consistent: no effect on serum IGF-1 and no adverse effect on carbohydrate metabolism across the trials (Stier et al., J Endocrinol Metab, 2013).

The honest position on the human evidence is stated plainly here. Safety and tolerability were reported as indistinguishable from placebo (Stier et al., J Endocrinol Metab, 2013), but efficacy in obesity was never established, the development programme was discontinued, and AOD-9604 holds no marketing authorisation in the UK or any other jurisdiction.

Storage and Reconstitution

Move vials to the freezer on arrival; the powder tolerates short transit at room temperature. To protect the disulfide, keep vials tightly sealed with little headspace, away from light and oxidising agents. Freeze single-use aliquots and thaw each one once, because repeated freeze-thaw drives aggregation.

Vials are sold on their own, without bacteriostatic water for mixing or other supplies.

How to reconstitute and handle

• AOD-9604 carries an intrachain disulfide bridge, so minimise air exposure and headspace when handling and re-seal vials promptly to limit oxidation.
• Avoid repeated freeze-thaw cycles; aliquot reconstituted stock into single-use volumes, label each with the reconstitution date, and work under aseptic conditions throughout.

For the full method, see the peptide reconstitution guide and the reconstitution calculator.

Research References

• Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone (Ng et al., Horm Res, 2000)
• 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 (Heffernan et al., Endocrinology, 2001)

Published research on AOD-9604 is indexed on PubMed. See our full UK buyer's guide for AOD-9604.