AOD-9604

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.

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.