Overview

AOD-9604 is a synthetic modification of the C-terminal fragment of human growth hormone corresponding to residues 176–191, with an additional N-terminal tyrosine. It was developed at Monash University in the 1990s during a research programme investigating whether the metabolic/lipolytic activity of the intact hormone could be dissociated from its growth-promoting and glucose-metabolism activities.

The peptide was subsequently investigated by Metabolic Pharmaceuticals as a candidate obesity therapeutic and has been the subject of small clinical trials. It has not received obesity-indication regulatory approval; in Australia it holds a GRAS-food-ingredient status only.

Mechanism (as reported in the literature)

  • Lipolytic activity. Animal studies report that AOD-9604 stimulates lipolysis in adipose tissue independent of the JAK2/STAT5 growth-signalling pathway used by the intact hGH molecule.
  • No IGF-1 elevation. Research characterises the fragment as not producing measurable increases in IGF-1, distinguishing its safety profile from GH-secretagogue peptides in the reported literature.
  • Beta-3 adrenergic signalling. Some rodent-study mechanistic work implicates activation of β3-adrenoceptor pathways in adipocytes.

Research findings

  • Rodent obesity models. Studies in genetically and diet-induced obese rodents report reductions in body-fat mass without changes in food intake, with preserved insulin sensitivity.
  • Phase-2 human trial. A 12-week randomised trial in obese adults reported modest reductions in body weight in the highest-dose group with a benign safety profile (Ng et al., 2000).
  • Cartilage repair investigations. Preclinical work has also characterised AOD-9604 in cartilage-repair models, though the peptide is best known for its metabolic-fragment research history.

Common dosing (from published research protocols)

Clinical-trial protocols used oral and subcutaneous doses in the low milligram range daily. Community research writeups typically describe 250–500 mcg subcutaneous administration daily.

Reconstitution

A 5 mg vial reconstituted with 2 mL of bacteriostatic water yields a 2,500 mcg/mL solution.

  • 250 mcg = 0.10 mL = 10 units on a U-100 syringe
  • 500 mcg = 0.20 mL = 20 units

Storage

Reconstituted AOD-9604 is refrigerated at 2–8 °C and reported as stable for approximately 30 days.

References

  • Ng, F. M., et al. (2000). “Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone.” Hormone Research, 53(6). PMID 10971089.
  • Heffernan, M. A., et al. (2001). “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, 142(12). PMID 11713217.
  • Wu, Z., et al. (1993). “Synthesis of a series of active carboxyl terminal peptides of human growth hormone.” International Journal of Peptide and Protein Research, 41(2). PMID 8444174.