AOD-9604
Also known as: hGH Fragment 176-191, Advanced Obesity Drug 9604
A modified 16-amino-acid fragment of human growth hormone studied for lipolytic effects without the growth-promoting activity of full-length hGH.
Molecular Data
- Class
- Modified 16-amino-acid hGH fragment / Lipolytic peptide
- Molecular Weight
- ~1,815 Da
- Molecular Formula
- C₇₈H₁₂₃N₂₃O₂₃S₂
- Half-Life
- Short (estimated, based on related hGH-fragment pharmacokinetic data)
- Sequence / Structure
- Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (hGH 176–191 fragment, Phe176→Tyr substitution, Cys7–Cys15 disulfide bridge)
Mechanism of Action
AOD-9604 corresponds to the C-terminal fragment of human growth hormone spanning residues 176–191, the region researchers at Monash University identified as responsible for hGH's fat-metabolizing activity. A tyrosine substitution at position 176 (replacing the native phenylalanine) was introduced to improve the fragment's stability.
- Lipolysis stimulation: AOD-9604 stimulates the breakdown of stored triglycerides into free fatty acids, the primary mechanism studied in obesity and lipid-metabolism research.
- Lipogenesis inhibition: Research indicates AOD-9604 also inhibits fat storage (lipogenesis), acting on both sides of the lipid-turnover balance.
- IGF-1-independent action: Unlike full-length hGH, AOD-9604 does not significantly raise IGF-1 levels, the basis for research interest in isolating hGH's metabolic effects from its growth-promoting effects.
- Cartilage research: Because the fragment retains structural relation to hGH, which has known roles in cartilage biology, AOD-9604 has also been studied in osteoarthritis and joint-health research models, independent of its metabolic mechanism.
Research History
AOD-9604 was developed by Monash University researchers and licensed to Metabolic Pharmaceuticals in the 1990s, based on earlier research identifying the hGH 176–191 fragment as the region responsible for the hormone's lipolytic, non-growth-promoting activity.
Metabolic Pharmaceuticals advanced AOD-9604 through six human clinical trials involving more than 900 participants, studying both subcutaneous (0.25, 0.5, and 1 mg daily) and oral (1, 5, 10, and 20 mg daily) dosing over periods up to 24 weeks. The subcutaneous 500 mcg/day dose was reported to show the most favorable efficacy-to-safety balance in early trials.
However, AOD-9604's largest Phase IIb trial failed to reach statistical significance for its primary weight-loss endpoint, and Metabolic Pharmaceuticals discontinued clinical development of the compound as an obesity treatment in 2007. It has not been approved by the FDA or any equivalent regulatory body for any indication. Research interest in AOD-9604 has since continued primarily in preclinical and mechanistic settings, including cartilage and joint-health research, rather than late-stage clinical development.
Notable Studies
Effects of Recombinant Peptide Fragments of Growth Hormone on Body Composition
2001Heffernan MA, Jiang WJ, Thorburn AW, Ng FM. · Obesity Research
Preclinical study demonstrating reductions in body fat with AOD-9604 administration in obese animal models without the growth-promoting effects of intact hGH.
Chronic Treatment with the C-Terminal Fragment of Growth Hormone Reduces Body Fat in Obese Mice
2000Ng FM, Sun J, Sharma L, et al. · Hormone and Metabolic Research
Investigated the lipolytic and lipogenesis-inhibiting effects of the hGH fragment in a diet-induced obesity mouse model.
AOD9604 and Lipid Metabolism
2000Dark GG, Ng FM, Bond PA, et al. · International Journal of Obesity
Examined AOD-9604's effects on lipid metabolism markers, part of the research basis for its subsequent clinical development.
Research Protocols
The following protocols describe doses used in published research studies. They are not prescriptions or recommendations for human use.
Phase II human clinical trials (Metabolic Pharmaceuticals)
- Dose
- 0.25 mg, 0.5 mg, or 1 mg (subcutaneous)
- Route
- Subcutaneous injection
- Frequency
- Once daily
- Duration
- 24 weeks
The 0.5 mg/day dose was reported to have the most favorable efficacy-to-safety ratio; the compound's largest Phase IIb trial did not reach statistical significance and clinical development was discontinued in 2007.