AOD-9604: HGH Fragment for Metabolic Research

EXOMA Scientific Team · Publicado el 13 de abril de 2026 · Actualizado el 17 de agosto de 2026

AOD-9604 (modified hGH 176-191 fragment): lipolytic mechanism without diabetogenic effects, comparison with HGH Frag and 5-Amino-1MQ. Scientific evidence.

What is AOD-9604?

AOD-9604 (Anti-Obesity Drug 9604) is a synthetic peptide that corresponds to a modified version of the C-terminal fragment of human growth hormone (hGH), specifically amino acids 176-191 with an additional tyrosine at the N-terminal end. It was developed by Metabolic Pharmaceuticals at Monash University, Australia.

Structure

• Sequence: Tyr-hGH(177-191) with a C-terminal disulfide bond
• Amino acids: 16 residues
• Molecular weight: ~1815 Da
• Key modification: Addition of Tyr at position 176 for stability

Mechanism of Action

AOD-9604 reproduces the lipolytic activity of GH without its effects on growth or glucose metabolism:

Lipolytic Activity

1. Activation of β3-adrenoceptors: Estimulación de la lipólisis en adipocitos
2. Inhibition of lipogenesis: Reducción de la síntesis de novo de ácidos grasos
3. Regulation of HSL: Activación de la lipasa sensible a hormonas
4. Fatty acid oxidation: Increase in mitochondrial β-oxidation

Absence of Diabetogenic Effects

Unlike full-length GH, AOD-9604:

• Does not affect IGF-1 levels: It does not stimulate hepatic IGF-1 production
• Does not alter blood glucose: No insulin resistance
• Does not promote growth: No anabolic effects on bone or tissue
• Does not affect prolactin or cortisol: Neutral endocrine profile

This is because the 176-191 region of GH contains the lipolytic domain but not the GH receptor (GHR) binding domain responsible for the growth-promoting and hyperglycemic effects.

Scientific Evidence

Preclinical Studies

Research at Monash University demonstrated:

• Obese murine models (ob/ob): Significant reduction of fat mass without change in lean mass
• Tissue selectivity: Preferential activity in visceral adipose tissue
• Dose-response: Dose-dependent lipolytic effect in isolated adipocytes
• Safety: No anti-GH antibodies generated

Clinical Studies

Phase II (Metabolic Pharmaceuticals, 2004):

• 300 obese patients (BMI 32-40)
• 12 weeks of oral treatment
• Modest but statistically significant results in weight reduction
• Favorable safety profile

Regulatory status in Australia (TGA):

• AOD-9604 received GRAS (Generally Recognized As Safe) classification from the FDA for use as a food ingredient
• Not approved as a drug in any jurisdiction

Comparison with Related Compounds

AOD-9604 vs HGH Fragment 176-191

AOD-9604 vs 5-Amino-1MQ

Both are studied in metabolism, but through distinct mechanisms:

NNMT and Metabolism

5-Amino-1MQ inhibits the enzyme nicotinamide N-methyltransferase (NNMT), which:

• Degrades nicotinamide, a precursor of NAD+
• It is overexpressed in adipose tissue of obese individuals
• Its inhibition increases cellular energy expenditure

Pharmacokinetics

• SC absorption: Rapid, Tmax ~15-30 minutes
• Half-life: ~60 minutes
• Oral bioavailability: Low (initial studies with a specialized oral formulation)
• Metabolism: Proteolysis
• Elimination: Renal

Research Protocols

In preclinical research, AOD-9604 is typically studied:

• Reconstitution: Bacteriostatic water
• Storage: -20°C (lyophilized), 2-8°C (reconstituted)
• Administration: Subcutaneous in animal models
• Study duration: 4-12 weeks

Important Considerations

Advantages for Research

• Well-characterized mechanism
• Clinical safety database (phase II)
• No interference with the GH/IGF-1 axis
• Compatible with other metabolic molecules

Limitations

• Modest clinical efficacy as monotherapy
• Requires parenteral administration for maximum bioavailability
• Incomplete phase III clinical studies

Conclusion

AOD-9604 represents a selective approach to modulating lipid metabolism, separating the lipolytic activity of GH from its growth-promoting and diabetogenic effects. Together with HGH Fragment 176-191 and 5-Amino-1MQ, it forms a group of research compounds for the study of the regulation of energy metabolism and adiposity.

Available at Exoma Peptides with certificate of analysis included.

References

Material for research use only. Verified primary sources supporting the scientific claims of this article:

1. Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274-278. doi:10.1159/000053183. PMID 11146367. (animal)
2. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. 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;142(12):5182-5189. doi:10.1210/endo.142.12.8522. PMID 11713213. (animal)
3. Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ, Ng FM. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001;25(10):1442-1449. doi:10.1038/sj.ijo.0801740. PMID 11673763. (animal)
4. Stier H, Vos E, Kenley D. Safety and tolerability of the hexadecapeptide AOD9604 in humans. J Endocrinol Metab. 2013;3(1-2):7-15. doi:10.4021/jem157w. (humano)

Products available at EXOMA

• AOD-9604