AOD-9604 Research Guide: The hGH (177-191) Fragment
By UK Peptide Lab Research Team•15 September 2026•8 min read
Key Takeaways
- AOD-9604 is Tyr-hGH(177-191): the 15-residue C-terminal fragment of human growth hormone with an N-terminal tyrosine added, MW 1815.12 g/mol, CAS 221231-10-3.
- The fragment retains the Cys6-Cys14 intrachain disulfide bridge of the native hGH C-terminus; the bridged conformation was characterised by Ogru et al. (J Pept Res, 2000).
- Preclinical rodent work reported lipolysis and fat oxidation without IGF-1-mediated growth or insulin-resistance effects (Ng et al., Horm Res, 2000; Heffernan et al., Endocrinology, 2001).
- Human efficacy was never established: the phase 2b programme was wound down with no marketing authorisation, though six RCTs reported a safety profile indistinguishable from placebo (Stier et al., J Endocrinol Metab, 2013).
What is AOD-9604?
AOD-9604 is a synthetic 16-residue peptide that reproduces the C-terminal region of human growth hormone. It consists of hGH residues 177-191 with an additional tyrosine at the N-terminus — sequence Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe, written YLRIVQCRSVEGSCGF and abbreviated Tyr-hGH(177-191) in the literature. Molecular weight is 1815.12 g/mol and the CAS number is 221231-10-3. The two cysteine residues, at positions 6 and 14, form an intrachain disulfide bridge, so the fragment retains the looped C-terminal conformation of the intact hormone — the 'cyclic anti-obesity peptide' analysed by NMR in the original conformational study (Ogru et al., J Pept Res, 2000). We supply AOD-9604 5mg as lyophilised powder.
From the hGH C-Terminus to a Drug Candidate
AOD-9604 was designed and developed by Metabolic Pharmaceuticals, the Melbourne-based company that screened C-terminal fragments of hGH for the lipid-mobilising activity of the intact hormone. The design goal was separation of effects: retain the lipolytic domain while discarding the growth-promoting and insulin-resistance actions that limit intact hGH as a therapeutic. That separation has a structural basis — AOD-9604 contains only the C-terminal domain and lacks binding site 2, the region intact hGH needs to dimerise its receptor and initiate growth signalling. The company took AOD-9604 through phase I into phase 2b clinical development in obesity before winding the programme down; it never received marketing authorisation.
The Published Preclinical Evidence
The primary literature on AOD-9604 is metabolic. Ng and colleagues (Horm Res, 2000) reported increased lipolytic activity in adipose tissue from obese Zucker rats treated with AOD9604 and concluded the fragment warranted development as an obesity agent. Heffernan and colleagues (Am J Physiol Endocrinol Metab, 2000) reported that oral administration of the fragment altered lipid metabolism in rats, and the group's follow-up in obese mice and β3-adrenergic receptor knock-out mice (Endocrinology, 2001) is the most-cited study in the field: chronic treatment reduced body weight and body fat, restored the depressed β3-adrenergic receptor expression of obese mice toward lean levels, and did so without raising IGF-1 or impairing glucose handling. The knock-out data are the mechanistic crux — mice lacking the β3 receptor showed no lipolytic response, implicating β3-adrenergic signalling in the fragment's activity. Related work characterised the disulfide-constrained conformation (Ogru et al., J Pept Res, 2000) and reported fat oxidation and weight loss with chronic hGH or fragment treatment (Heffernan et al., Int J Obes Relat Metab Disord, 2001).
What the Clinical Programme Actually Showed
Human data exist, and they are worth reading in the original. Stier, Vos and Kenley (J Endocrinol Metab, 2013) summarised six randomised, double-blind, placebo-controlled trials — phase I intravenous dose-ranging through to two phase 2b efficacy studies of 12 and 24 weeks in 300 and 502 obese adults respectively. The findings: no effect on serum IGF-1, no adverse effect on carbohydrate metabolism, no anti-AOD-9604 antibodies detected, and a safety and tolerability profile indistinguishable from placebo. What the publication does not contain is established efficacy, and this is the honest boundary of the AOD-9604 story. Metabolic Pharmaceuticals wound down development of the compound, no phase 3 efficacy data were ever published, and AOD-9604 holds no marketing authorisation in the UK or any other jurisdiction. It remains a research peptide, and the safety literature should not be read as evidence of benefit.
AOD-9604 vs hGH Fragment 177-191
Both compounds are built on the same 15-residue C-terminal sequence. hGH Fragment 177-191 is the unmodified peptide LRIVQCRSVEGSCGF; AOD-9604 is that sequence with an N-terminal tyrosine added, giving sixteen residues and raising the molecular weight from approximately 1617 to 1815.12 g/mol. Both retain the Cys6-Cys14 disulfide bridge, and both have been studied for lipolytic activity without the IGF-1-mediated growth effects of intact hGH. The difference is provenance rather than pharmacology: the unmodified fragment is the reference sequence in the primary literature, while AOD-9604 is the developed candidate that carried the clinical programme. Direct head-to-head comparisons are scarce, so laboratories selecting between them are mostly choosing between the reference molecule and the clinically characterised one.
AOD-9604 vs Full-Length HGH
The contrast with the intact hormone is the entire rationale for the fragment. hGH is a 191-residue protein with two receptor binding sites; AOD-9604 is sixteen residues with one. Without binding site 2, the fragment cannot dimerise the hGH receptor, and the published human data bear this out: across the six trials summarised by Stier and colleagues, AOD-9604 produced no change in serum IGF-1 and no impairment of glucose tolerance — precisely the effects intact hGH is known for. Preclinical work in obese mice reported the same separation, with lipolysis and fat oxidation but no growth-promoting or insulin-resistance effects (Heffernan et al., Endocrinology, 2001). That separation of activity, not any enhancement of it, is what makes the fragment interesting to study.
Laboratory Handling, Reconstitution and Storage
AOD-9604 is supplied as a lyophilised white powder and should be stored at -20°C, protected from light and moisture. Reconstitute with bacteriostatic water: allow the vial to reach room temperature, swab the stopper, inject the solvent slowly down the inner glass wall rather than onto the cake, and swirl gently — never shake or vortex. The solution should be clear and colourless. Because the fragment carries an intrachain disulfide bridge, treat oxidation as the failure mode to design against: keep headspace minimal, re-seal vials promptly and avoid unnecessary air exposure. Reconstituted solution held at 2-8°C should be used within approximately four weeks; for longer storage, aliquot into single-use volumes at -20°C and thaw each aliquot once. Work aseptically throughout, and see our complete reconstitution guide for the fuller protocol. For in-vitro laboratory research only.
Sourcing Research-Grade AOD-9604 in the UK
UK Peptide Lab supplies AOD-9604 5mg at £34.99 as lyophilised powder, batch UKPL-9502, supplier-reported 99.92% purity by RP-HPLC. Independent third-party verification is in progress and the certificate will be published on the product page once complete. The batch number printed on the vial matches the batch reference shown on this page. Orders placed before 2pm GMT dispatch the same day, with free Royal Mail Tracked shipping on UK orders over £45. AOD-9604 is supplied strictly for in-vitro laboratory research use, is not a licensed medicine anywhere, and purchasers must be 18 or over.
Related Products
Disclaimer: This article is for research and educational purposes only. All information provided is not intended as medical advice. UK Peptide Lab products are not for human consumption and are sold strictly for laboratory research use only.
Frequently Asked Questions
What is AOD-9604?
AOD-9604 is a synthetic 16-residue peptide matching residues 177-191 of human growth hormone with an extra N-terminal tyrosine: sequence YLRIVQCRSVEGSCGF, molecular weight 1815.12 g/mol, CAS 221231-10-3. The cysteines at positions 6 and 14 form an intrachain disulfide bridge that keeps the fragment in the looped C-terminal conformation of native hGH. It was developed by Metabolic Pharmaceuticals as an anti-obesity candidate and is supplied for in-vitro laboratory research only.
Does AOD-9604 raise IGF-1?
No. The published summary of six randomised, double-blind, placebo-controlled clinical trials reports no effect on serum IGF-1 at any dose tested, and no adverse effect on carbohydrate metabolism, in contrast to intact hGH (Stier et al., J Endocrinol Metab, 2013). Preclinical work in obese mice reported the same separation, with lipolysis but no IGF-1-mediated growth effects (Heffernan et al., Endocrinology, 2001). Structurally this follows from the fragment lacking hGH binding site 2, which the intact hormone needs to dimerise its receptor.
How should AOD-9604 be reconstituted and stored?
Reconstitute with bacteriostatic water injected slowly down the inner glass wall, then swirl gently until clear and colourless; never shake or vortex. Store lyophilised vials at -20°C protected from light and moisture, and hold reconstituted solution at 2-8°C, using within approximately 4 weeks. The intrachain disulfide bridge makes oxidation the main degradation route, so minimise headspace and re-seal promptly. AOD-9604 is supplied for in-vitro laboratory research use only.
References
- [1] Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research (2000). View →
- [2] Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. American Journal of Physiology – Endocrinology and Metabolism (2000). View →
- [3] 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. Endocrinology (2001). View →
- [4] The conformational and biological analysis of a cyclic anti-obesity peptide from the C-terminal domain of human growth hormone. Journal of Peptide Research (2000). View →
- [5] Safety and tolerability of the hexadecapeptide AOD9604 in humans. Journal of Endocrinology and Metabolism (2013). View →