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AOD-9604: Growth Hormone C-Terminal Fragment Research Overview

AOD-9604 (Anti-Obesity Drug 9604) is a synthetic peptide representing residues 177-191 of growth hormone's C-terminal region, with a tyrosine modification to enhance stability. The compound was designed to capture the lipolytic signaling of full-length growth hormone in a smaller peptide. This page summarizes the published preclinical research.

Last reviewed: 2026-05-11· Instant Peptides Research Team
Research-use reference only. The content below summarizes published preclinical and in vitro research. Not for human or animal consumption, diagnostic, or therapeutic use. Information is provided as an educational resource for qualified research professionals.

Background

AOD-9604 was developed by researchers at Monash University and Metabolic Pharmaceuticals in the 1990s. The compound is based on residues 177-191 of human growth hormone (hGH) — the C-terminal region that early research had identified as carrying lipolytic activity distinct from the growth-stimulating activity of the full peptide.[1]

The peptide includes a tyrosine residue added to the N-terminus of the hGH(177-191) fragment, both for synthetic accessibility and for enhanced stability in research preparations. The full sequence is sometimes designated Tyr-hGH(177-191).[2]

AOD-9604 is studied as a research reference compound in preclinical lipid metabolism and growth hormone fragment biology. It has not been approved by the FDA for any human therapeutic or medical purpose.

Chemistry & Structure

AOD-9604 structural features:

  • Sequence: Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (16 amino acids: Tyr added to native hGH 177-191)
  • Native parent region: hGH 177-191
  • N-terminal modification: tyrosine residue
  • Disulfide bond: one (between the two cysteine residues at positions 7 and 14 of AOD-9604)
  • Molecular formula: C₇₈H₁₂₃N₂₃O₂₃S₂
  • Molecular weight: approximately 1,815 Da

Structural rationale

Early research with hGH fragments established that the C-terminal region carries lipolytic signaling without the IGF-1-mediated growth effects of full GH. The 177-191 fragment was identified as the minimal active sequence for this lipolytic activity, and Tyr-hGH(177-191) became the canonical research peptide for studying GH C-terminal fragment biology.[1]

The disulfide bond between the two cysteines is essential for the peptide's three-dimensional structure and its biological activity. Maintaining the correct disulfide pairing is therefore important during synthesis and storage.

Mechanism Research

AOD-9604's research-characterized mechanisms focus on lipid metabolism pathways.

Lipolytic signaling

Cell-based studies in adipocyte preparations have characterized AOD-9604 effects on triglyceride hydrolysis. The compound has been associated with increased lipolysis through pathways downstream of the GH C-terminal signaling region, distinct from the growth hormone receptor-mediated effects of full GH.[3]

Receptor pharmacology

Unlike full GH, AOD-9604 does not engage the GH receptor productively. The exact receptor(s) mediating its effects in cell-based preparations have remained an active area of research, with some studies suggesting beta-3 adrenergic receptor cross-talk or distinct uncharacterized receptors.[4]

Documented Preclinical Research Areas

AOD-9604 research is concentrated in metabolic and adipose tissue preclinical studies.

Adipocyte lipolysis studies

Cultured adipocytes (3T3-L1 cell line and primary adipocytes) are standard substrates for AOD-9604 research. Endpoints include glycerol release, triglyceride content measurement, and lipase enzyme activity.[3]

Animal obesity models

Rodent models of diet-induced obesity have included AOD-9604 in experimental arms examining body composition endpoints, adipose tissue mass, and metabolic markers.[4]

Joint and cartilage research

A secondary research line has examined AOD-9604 effects in cartilage and joint tissue preclinical models, possibly mediated by separate pathways than the lipolytic activity.[5]

Stability & Handling

AOD-9604's disulfide bond requires careful handling to maintain integrity.

Storage

Lyophilized AOD-9604 is stored at minus 20 degrees Celsius. The disulfide-containing structure is sensitive to repeated freeze-thaw and to reducing conditions.

Reconstitution

Bacteriostatic water is the standard reconstitution solvent. Care should be taken to avoid reducing agents in the reconstitution buffer.

Quality verification

HPLC for purity, mass spectrometry for identity confirmation, and verification of correct disulfide pairing by reduced/oxidized peptide mapping. Each batch of Instant Peptides AOD-9604 ships with a full Certificate of Analysis.

Available Research Material

Instant Peptides supplies AOD-9604 as a synthetic lyophilized reference compound. Material is supplied to qualified research professionals. Not for human or animal consumption.

View the product page for current pricing and the Certificate of Analysis for the active batch.

Available Research Material

AOD-9604

Lyophilized synthetic reference compound. Independently tested for purity by HPLC and mass spectrometry. Full Certificate of Analysis included.

View product details

References

  1. 1.Heffernan M, Summers RJ, Thorburn A, et al. 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. PMID: 11606480
  2. 2.Ng FM, Sun J, Sharma L, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research. 2000. PMID: 11050208
  3. 3.Stier H, Vos E, Kenley D. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism. 2013.
  4. 4.Heffernan MA, Thorburn AW, Fam B, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International Journal of Obesity. 2001. PMID: 11595961
  5. 5.Kwon DR, Park GY. Effect of Intra-Articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Annals of Clinical & Laboratory Science. 2015. PMID: 26537687

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