AOD-9604

What is AOD-9604?

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, written YLRIVQCRSVEGSCGF, molecular weight 1815.12 g/mol, CAS 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 native hormone, the 'cyclic anti-obesity peptide' characterised by NMR in the original conformational analysis by Ogru and colleagues (J Pept Res, 2000). AOD-9604 was developed by Metabolic Pharmaceuticals (Melbourne, Australia) as an anti-obesity candidate: the company isolated the lipid-mobilising domain of hGH from its growth-promoting and insulin-resistance effects, and carried the compound through phase 2b clinical development before winding the programme down. Supplied as lyophilised powder for in-vitro research use only, not currently a licensed medicine anywhere.

AOD-9604 vs hGH Fragment 177-191

The two compounds share the same 15-residue C-terminal backbone of human growth hormone and the same disulfide-bridged loop structure; what separates them is a single amino acid. hGH Fragment 177-191 is the unmodified 15-residue sequence, Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe, molecular weight approximately 1617 g/mol. AOD-9604 is that exact sequence with an N-terminal tyrosine added, giving sixteen residues and a molecular weight of 1815.12 g/mol (CAS 221231-10-3). Both carry the intrachain disulfide bridge between the cysteine residues at positions 6 and 14, the feature that constrains the fragment into the looped conformation of the native hGH C-terminus characterised by Ogru and colleagues (J Pept Res, 2000). Both have been studied for lipolytic activity in rodent models without the IGF-1-mediated growth effects of intact hGH. The practical difference is provenance. The unmodified fragment is the reference sequence in the primary metabolic literature, whereas AOD-9604 is the developed candidate that Metabolic Pharmaceuticals carried through phase 2b clinical development (Stier et al., J Endocrinol Metab, 2013). Researchers choosing between them are effectively choosing between the reference molecule and the clinically characterised one; published head-to-head comparisons are scarce, so the added tyrosine should be treated as the variable of interest.

AOD-9604 Research Applications

AOD-9604 is used in metabolic research on the lipolytic domain of human growth hormone: hormone-stimulated lipolysis and fatty-acid oxidation assays in adipocyte and rodent models, comparative pharmacology of intact hGH against its C-terminal fragments, and study designs that separate the lipid-mobilising activity of hGH from its IGF-1-mediated growth effects. The core characterisation is Ng and colleagues (Horm Res, 2000), who 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 work 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 liabilities of intact hGH. A further line of work characterises the disulfide-bridged conformation of the fragment (Ogru et al., J Pept Res, 2000). The honest boundary: human efficacy was never established, the phase 2b programme was wound down without a marketing authorisation anywhere, and material supplied here is for in-vitro laboratory research only.

Reconstitution Guide

Allow the vial to reach room temperature, then sterilise the rubber stoppers of both the peptide vial and the bacteriostatic water vial with an alcohol swab. Slowly draw bacteriostatic water into a sterile syringe and inject it gently down the inner glass wall of the peptide vial, never directly onto the lyophilised cake. Swirl the vial slowly in a circular motion until the powder is fully dissolved and the solution is clear and colourless; never shake or vortex, as mechanical shear and foaming degrade the peptide. AOD-9604 carries an intrachain disulfide bridge between the cysteine residues at positions 6 and 14, so treat oxidation as the degradation route to design against: work efficiently, avoid introducing excess air into the vial, and re-seal promptly after each draw. Use sterile, pyrogen-free consumables throughout and work in a laminar flow hood where available. If the solution appears turbid or the cake fails to dissolve completely, discard the vial rather than forcing dissolution — turbidity indicates aggregation or contamination, and partially aggregated material will not give reproducible assay results. Record the reconstitution date, solvent volume and resulting concentration on the vial label, then refrigerate immediately. For in-vitro laboratory research use only.

See our full peptide reconstitution guide and reconstitution calculator for step-by-step protocol.

Storage Instructions

Store lyophilised vials at -20°C, protected from light and moisture, for long-term stability of up to 24 months; the lyophilised cake tolerates short transit at ambient temperature but should be moved to the freezer on receipt. Once reconstituted with bacteriostatic water, hold the solution at 2-8°C (standard refrigerator) and use within approximately 4 weeks, as hydrolysis proceeds once the peptide is in solution. For storage beyond that, prepare single-use aliquots at -20°C and thaw each aliquot only once; repeated freeze-thaw cycles are the fastest route to aggregation and loss of intact material. The degradation route to design against with AOD-9604 is oxidation of the intrachain disulfide between the cysteines at positions 6 and 14: keep vials tightly sealed with minimal headspace, protect from light, and never store the solution in contact with oxidising agents. Handle under sterile laboratory conditions throughout, discard any solution that becomes turbid, and keep the batch number and certificate of analysis on file for experimental records. For in-vitro laboratory research use only.

Frequently Asked Questions

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)

Related Research Compounds

• → Tesamorelin 5mg
• → Ipamorelin 5mg
• → Bacteriostatic Water 10ml