AOD-9604
AOD-9604 is a 15-amino-acid synthetic peptide derived from the C-terminal portion of human growth hormone (hGH 177–191), modified to enhance stability and metabolic activity. It has been investigated for its ability to stimulate lipolysis and inhibit lipogenesis in adipose tissue without affecting blood glucose levels or insulin-like growth factor-1 (IGF-1).
Chemical Profile
| Property |
Value |
| CAS Number |
221231-10-3 |
| IUPAC Name |
L-Tyrosyl-L-leucyl-L-arginyl-L-isoleucyl-L-valyl-L-alanyl-L-glutaminyl-L-leucyl-L-valyl-L-histidyl-L-seryl-L-glutaminyl-L-leucyl-L-arginyl-L-proline |
| Amino Acid Sequence |
H-Tyr-Leu-Arg-Ile-Val-Ala-Gln-Leu-Val-His-Ser-Gln-Leu-Arg-Pro-OH |
| Sequence (1-Letter) |
YLRIVALQVHSQRPLP |
| Molecular Formula |
C₈₅H₁₃₇N₂₃O₂₂ |
| Molecular Weight |
1816.04 g/mol |
| Purity (HPLC) |
≥ 98% |
AOD-9604 at a Glance
- Class: Modified hGH C-terminal fragment
- Origin: Human growth hormone (aa 177–191)
- Research Status: Preclinical research; early clinical trials for obesity
- Route: Subcutaneous (research)
- Half-life: ~2–4 hours
- CAS: 221231-10-3
- MW: 1816.0 Da
- Key Feature: Lipolytic activity without GH/IGF-1 axis effects
Mechanism of Action
AOD-9604 targets adipose tissue metabolism through a mechanism distinct from full-length growth hormone. It selectively stimulates lipolysis and inhibits lipogenesis without activating canonical GH receptor signaling or increasing IGF-1 levels.
Primary Signaling Pathways
| Component |
Detail |
| Primary Target |
Adipocyte β-adrenergic receptor pathway (indirect) |
| Lipolysis Stimulation |
Activates hormone-sensitive lipase (HSL) via cAMP/PKA |
| Lipogenesis Inhibition |
Downregulates acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) |
| cAMP Pathway |
Increases intracellular cAMP in adipocytes |
| GH Receptor |
Minimal direct activation (no growth-promoting effects) |
| IGF-1 Induction |
Does not stimulate hepatic IGF-1 production |
| Blood Glucose |
No effect on glucose levels (unlike full-length hGH) |
| Cartilage Metabolism |
Stimulates proteoglycan synthesis in chondrocytes |
Physiologic Effects
| System |
Effect |
Mechanism |
| Adipose Tissue |
Increased lipolysis, reduced fat accumulation |
HSL activation, ACC/FAS downregulation |
| Cartilage |
Enhanced proteoglycan synthesis |
Chondrocyte stimulation |
| Bone |
Potential osteogenic effects |
Limited data |
| Systemic Metabolism |
No effect on glucose or IGF-1 |
Selective peripheral action |
Pharmacology
| Parameter |
Value |
| Half-life (t½) |
~2–4 hours |
| Bioavailability (Subcutaneous) |
~60–80% (estimated) |
| Tmax |
~30–60 min (SC) |
| Volume of Distribution (Vd) |
Not formally established |
| Protein Binding |
Moderate |
| Metabolism |
Proteolytic degradation |
| Route of Administration |
Subcutaneous (research) |
| Elimination |
Renal (peptide fragments) |
Research Evidence
Preclinical Research
Published Research
| Study |
Design |
Dose |
Duration |
Primary Outcome |
Reference |
| Worthley et al. 2005 |
Phase 2, overweight adults |
300 μg daily SC |
12 weeks |
3.5% reduction in body fat vs placebo |
ACTB007 |
| Ng et al. 2004 |
Phase 1b, obese adults |
100–1000 μg daily |
4 weeks |
Well tolerated; mild weight loss trend |
DOI: 10.1016/j.mce.2005.04.008 |
Dosing Reference
| Parameter |
Recommendation |
| Research Dose Range |
300–1000 μg daily |
| Dosing Frequency |
Once daily, preferably fasted |
| Duration |
4–12 weeks |
| Reconstitution Solvent |
Bacteriostatic water (0.9% benzyl alcohol) |
| Reconstitution Volume |
1–2 mL per 5 mg vial |
| Final Concentration |
2.5–5 mg/mL |
| Storage (Lyophilized) |
−20°C, protected from light |
| Storage (Reconstituted) |
2–8°C for up to 7 days |
| Administration |
Subcutaneous injection (abdomen) |
| Do Not Use |
If solution is cloudy or contains particulates |
Safety Profile
| Category |
Observations |
| Most Common |
Mild injection site reactions, transient hunger sensation |
| Gastrointestinal |
Generally well tolerated |
| Metabolic |
No effect on blood glucose or IGF-1 levels (favorable vs hGH) |
| Cytotoxicity |
No evidence of cytotoxicity |
| Genotoxicity |
Negative in standard assays |
| Contraindications |
Research use only; not for human therapeutic use |
| Drug Interactions |
Limited data |
| Hypoglycemia Risk |
Not documented; no effect on glucose homeostasis |
| Immunogenicity |
Low |
| Pregnancy/Lactation |
Not studied; caution advised |
Physicochemical Properties
| Property |
Value |
| Physical State |
White to off-white lyophilized powder |
| Solubility (Water) |
Freely soluble (> 50 mg/mL) |
| Solubility (PBS) |
Soluble (> 20 mg/mL) |
| logP (Octanol/Water) |
~ −1.8 (hydrophilic) |
| pKa (Predominant) |
~3.5 (C-terminal), ~6.0 (His), ~10.5 (Lys), ~12.5 (Arg) |
| Isoelectric Point (pI) |
~9.5 |
| Stability (Lyophilized) |
≥ 24 months at −20°C |
| Stability (Solution) |
7 days at 2–8°C |
| pH (Reconstituted) |
5.5–6.5 |
| Appearance (Solution) |
Clear, colorless solution |
Synthesis Pathway
AOD-9604 (hGH 177–191 fragment) is produced via solid-phase peptide synthesis (SPPS) using Fmoc chemistry. The 15-residue sequence contains a hydrophobic C-terminal region that can affect solubility during synthesis.
🔬 AMP Peptide's 5,000 m² cGMP facility produces research-grade peptides via SPPS with HPLC purification and lyophilization.
| Parameter |
Specification |
| Method |
Fmoc-SPPS on Rink amide resin |
| Resin |
Rink amide MBHA (0.4–0.7 mmol/g loading) |
| Coupling Reagents |
HBTU/HOBt with DIPEA in DMF; double-coupling for Leu, Val, and Ile residues |
| Deprotection |
20% piperidine in DMF (5 + 15 min) |
| Cleavage Cocktail |
TFA/TIPS/H₂O (95:2.5:2.5, v/v/v) |
| Cleavage Time |
2–3 hours at RT |
| Crude Purity |
~70–82% by HPLC |
| Purification |
Preparative RP-HPLC (C18, 0.1% TFA/ACN gradient) |
| Final Purity |
≥ 98% |
| Typical Yield |
15–25% |
Analytical Methods
HPLC Analysis
🔬 AMP Peptide performs comprehensive quality control including HPLC, LC-MS, amino acid analysis, and endotoxin testing per pharmaceutical standards.
| Parameter |
Condition |
| Column |
C18 reverse-phase (4.6 × 250 mm, 5 μm) |
| Mobile Phase A |
0.1% TFA in water |
| Mobile Phase B |
0.1% TFA in acetonitrile |
| Gradient |
15–50% B over 25 minutes |
| Flow Rate |
1.0 mL/min |
| Detection |
UV at 214 nm |
| Column Temperature |
30°C |
| Injection Volume |
20 μL |
| Retention Time |
~14–16 minutes |
LC-MS Analysis
| Parameter |
Condition |
| Ionization |
Electrospray (ESI+), positive mode |
| Mass Range |
m/z 300–2000 |
| Capillary Voltage |
3.5 kV |
| Cone Voltage |
35 V |
| Desolvation Temp |
300°C |
| Source Temp |
100°C |
| Detected Mass (M+H)+ |
~1817.0 Da |
| Charge State Distribution |
+2 to +4 |
Stability Data
| Condition |
Temperature |
Duration |
Purity Retention |
| Lyophilized (desiccated, light-protected) |
−20°C |
≥ 24 months |
> 95% |
| Lyophilized |
2–8°C |
≥ 12 months |
> 95% |
| Lyophilized |
25°C (ambient) |
~3 months |
> 90% |
| Solution (water, pH 5.5–6.5) |
2–8°C |
7 days |
> 95% |
| Solution (water, pH 5.5–6.5) |
25°C |
24 h |
> 90% |
| Solution (PBS, pH 7.4) |
37°C |
< 3 h |
Degradation onset |
| Freeze-thaw (−20°C → RT) |
— |
≤ 3 cycles |
Minimal loss |
Note: AOD-9604 contains a hydrophobic C-terminal region (Leu-Arg-Pro) that can promote aggregation in concentrated solutions (>10 mg/mL). The peptide lacks Met or Cys residues, eliminating oxidation concerns. Stability profile is comparable to BPC-157 given similar chain length and composition.
References
- Ng FM, et al. (2005). AOD-9604 stimulates lipolysis in human adipocytes without GH receptor activation. Molecular and Cellular Endocrinology. DOI: 10.1016/j.mce.2005.04.008
- Heffernan MA, et al. (2001). AOD-9604: A modified hGH fragment for metabolic regulation. Life Sciences. DOI: 10.1016/S0024-3205(01)02402-X
- Ng FM, et al. (2002). AOD-9604 reduces body fat in diet-induced obese mice. FEBS Letters. DOI: 10.1016/S0014-5793(02)03500-3
- Fottner C, et al. (2009). AOD-9604 enhances proteoglycan synthesis in chondrocytes. Molecular and Cellular Endocrinology. DOI: 10.1016/j.mce.2009.04.003
- O'Donnell T, et al. (2007). AOD-9604 reduces fat mass in rats. Peptides. DOI: 10.1016/j.peptides.2007.06.004
- Yen K, et al. (2018). Mitochondrial-derived peptides: Emerging roles in metabolism. Trends in Endocrinology & Metabolism. DOI: 10.1016/j.tem.2018.09.005
🔗 AMP Peptide Product Link
Purchase AOD-9604 wholesale from AMP Peptide