AOD-9604

A detailed technical summary of the synthetic peptide fragment AOD-9604 (Tyr-hGH177-191), covering its chemical structure, original development context, and investigated mechanisms in metabolic research models.

Peptide Name
AOD-9604 (Tyr-hGH177-191)
Type
Synthetic Peptide Fragment
Sequence Length
16 Amino Acids
CAS Number
221231-10-3
Primary Research Focus
Lipid Metabolism & Cartilage Tissue Modeling
Key Distinction
Lacks IGF-1 stimulating effects of full-length hGH
Molecular Formula
C₇₈H₁₂₃N₂₃O₂₃S₂
Molecular Weight
1815.1 Da
Amino Acid Sequence
Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe
Structure Note
A disulfide bridge typically exists between Cys7 and Cys15, creating a cyclic domain critical for conformational stability and receptor binding affinity.
Store powder at +4°C (short term) or -20°C (long term). Keep desiccated.
AOD-9604 is commonly reconstituted in either bacteriostatic or sterile water in research environments. Selection depends on experimental design, handling frequency, and stability requirements. This information is provided for laboratory education only.
Amino Acid Sequence
  • AOD-9604 was originally developed by Metabolic Pharmaceuticals (Australia) in the late 1990s. The peptide was engineered following findings that the C-terminal region of hGH was responsible for lipid mobilization.
  • The addition of a tyrosine residue at the N-terminus (Tyr-hGH177-191) was intended to improve stability and reduce rapid enzymatic degradation, potentially allowing for oral bioavailability—an uncommon feature among peptide therapeutics.

Research in murine (mouse/rat) and in-vitro models suggests AOD-9604 may modulate lipid metabolism via two primary pathways:

  • Stimulation of Lipolysis Increased breakdown of stored triglycerides into free fatty acids and glycerol.
  • Inhibition of Lipogenesis Reduction in the synthesis and deposition of new fat in adipose tissue.

Mechanistic Note: Unlike hGH, which signals through the hGH receptor to stimulate IGF-1, AOD-9604 is hypothesized to interact with beta-3 adrenergic receptors on adipocytes. The precise receptor binding profile remains under investigation.

Biological Effect Full-Length hGH AOD-9604 Fragment
Lipolysis Potent Retained (in models)
IGF-1 Stimulation High (Anabolic) None / Negligible
Insulin Resistance Promotes None observed
Cell Proliferation Stimulates No significant effect
  • Between 2000 and 2007, Metabolic Pharmaceuticals conducted six clinical trials involving over 900 patients. Early intravenous studies demonstrated acute lipolytic effects.
  • However, large Phase IIb oral trials produced mixed results. Despite a favorable safety profile, the peptide did not achieve statistically significant body-weight modulation across the broader trial population, leading to discontinuation of pharmaceutical development in 2007.
  • Cartilage Tissue Modeling Post-2010 rat models of collagenase-induced osteoarthritis suggest intra-articular AOD-9604 may influence cartilage matrix interactions, potentially affecting chondrocyte proliferation or differentiation.
  • Cardiovascular Health Preliminary rodent studies have explored effects on lipid profiles and cardiovascular markers, though these datasets remain limited.
  • Bioavailability Challenges: Oral bioavailability remains a significant hurdle in peptide therapeutics.
  • Short Half-Life: Requires frequent administration in research protocols.
  • Regulatory Status: Not FDA-approved; human efficacy claims are extrapolated from animal data.

 

 

  • Ng, F. M., et al. (2000). Journal of Endocrinology, 166(1), 75-85.

  • Heffernan, M., et al. (2001). Diabetes, Obesity and Metabolism, 3(6), 424-435.

  • Kwon, D. R., & Park, G. Y. (2011). Annals of Clinical & Laboratory Science, 41(3), 219-225.

  • Stier, H., et al. (2013). Journal of Endocrinology and Metabolism, 3(1-2), 7-15.

The compound listed below is referenced in research contexts related to the mechanisms discussed in this article.
The compound AOD-9604 discussed on this page is a chemical standard intended strictly for in-vitro and laboratory research applications (e.g., receptor binding assays, cell culture studies). It is not a drug, dietary supplement, or food additive. It is not intended for human consumption, injection, or therapeutic use. All handling must be performed by qualified professionals in a laboratory setting.

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