What Is AOD-9604?
Quick Answer
AOD9604 (Anti-Obesity compound 9604) is a synthetic hexadecapeptide analog of the C-terminal fragment of human growth hormone (hGH), specifically corresponding to amino acid residues 177–191 with an additional tyrosine residue at the N-terminus to enhance stability [1][2]. It was originally develope...
AOD9604 (Anti-Obesity compound 9604) is a synthetic hexadecapeptide analog of the C-terminal fragment of human growth hormone (hGH), specifically corresponding to amino acid residues 177–191 with an additional tyrosine residue at the N-terminus to enhance stability [1][2]. It was originally developed at Monash University (Melbourne, Australia) by research teams led by Dr. Frank M. Ng to retain the lipolytic (fat-burning) properties of hGH without inducing its insulin-desensitizing or mitogenic (growth-promoting) reported observations in study populations [3][4].
The peptide was subsequently licensed to Metabolic Pharmaceuticals Ltd (ASX: MBP), which advanced AOD9604 through preclinical and early clinical development between 1999 and 2007. The compound has attracted renewed scientific interest in the context of musculoskeletal repair research, with studies exploring its effects on cartilage regeneration in animal models of osteoarthritis [5][6]. More recently, under the code name LAT8881, it has been investigated for potential host-protective properties against severe influenza A virus infection [7].
Structurally, AOD9604 is a 16-amino-acid peptide with a molecular weight of 1815.1 g/mol. It contains a disulfide bridge between Cys7 and Cys14 (corresponding to Cys182 and Cys189 in native hGH), which forms a cyclic domain critical for biological activity [8]. The addition of a tyrosine residue at the N-terminus distinguishes AOD9604 from the native hGH(177–191) fragment, conferring improved metabolic stability and potency in preclinical lipid-metabolism assays [2][9].
References
- Heffernan, M., et al. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic research application in obese mice and beta(3)-AR knock-out mice. Endocrinology, 142(12), 5182-5189.
- Ng, F. M., et al. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research, 53(6), 274-278.
- Ng, F. M. & Bornstein, J. (1978). Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. Am J Physiol, 235(1), E55-E59.
- Ng, F. M., et al. (2000). Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. J Mol Endocrinol, 25(3), 287-298.
- Kwon, D. R. & Park, G. Y. (2015). Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci, 45(4), 426-432.
- Kwon, D. R., et al. (2020). Regenerative effects of intra-articular injection of AOD 9604 combined with hyaluronic acid in a rabbit model of collagenase-induced osteoarthritis. compound Des Devel Ther, 14, 2193-2201.
- Lateral Pharma Pty Ltd. (2020). LAT8881 (AOD9604) host-protective experimental protocol for influenza A virus infection. Clinical development update.
- Wu, Z., et al. (1993). The structural determinants of the lipolytic fragment (residues 177-191) of human growth hormone. Int J Pept Protein Res, 41(5), 432-438.
- Ng, F. M., et al. (1990). Action of a synthetic lipotropic peptide of human growth hormone on lipogenesis in rats. J Mol Endocrinol, 5(3), 265-271.
- Heffernan, M., et al. (2000). The effects of AOD9604 on beta-3 adrenergic receptor expression and lipolysis in obese mice. Obesity Research, 8(S1), abstract.
- Groenewegen, W. A., et al. (2004). Oral AOD9604 reduces body fat in Zucker rats by selective fat mass reduction without effect on lean body mass. Appetite, 42(3), abstract.
- Ng, F. M. & Roupas, P. (1999). Anti-lipogenic action of the C-terminal fragment 177-191 of human growth hormone. Res Commun Mol Pathol Pharmacol, 106(1-2), 35-48.
- Tomer, Y. & Bhargava, A. S. (1999). Growth hormone receptor and signal transduction. In: Molecular Biology of Growth Hormone Receptors. Springer.
- Wu, Z., et al. (1994). Mapping the functional domains of human growth hormone required for metabolic activity. J Biol Chem, 269(22), 15523-15530.
- Stier, H., et al. (2013). tolerability and Tolerability of the Hexadecapeptide AOD9604 in Humans. J Endocrinol Metab, 3(1-2), 7-15.
- Metabolic Pharmaceuticals Limited. (2007). Metabolic’s obesity compound – Phase 2B clinical trial results. ASX Announcement, 27 June 2007.
- Thompson, G., et al. (2004). Phase 2b clinical trial results for AOD9604. Presented at the International Congress on Obesity.
- Kwon, D. R., et al. (2019). Regenerative effects of AOD9604 with or without hyaluronic acid on tendon healing in a rat Achilles tendon injury model. compound Des Devel Ther, 13, 4173-4186.
- Stier, H. & Kenley, D. (2012). Preclinical and clinical tolerability review of AOD9604. Regul Toxicol Pharmacol, 64(2), S34-S35.
- U.S. Food and Drug Administration. (2023). Bulk Drug Substances Used in Compounding Under Section 503B. FDA.gov.
- World Anti-Doping Agency. (2024). The Prohibited List: International Standard. Section S2.
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