Anti-Obesity Drug Fragment 9604
AOD-9604 | hGH Fragment 176-191 | Tyr-hGH177-191
Mechanism of Action
AOD-9604 is a modified fragment of human growth hormone (hGH) spanning amino acids 176-191, with an added tyrosine at the N-terminus to enhance stability. It was developed to isolate the lipolytic (fat-burning) activity of growth hormone from its growth-promoting and diabetogenic effects. The peptide stimulates lipolysis and inhibits lipogenesis through a mechanism distinct from the GH receptor, and notably does not induce IGF-1 production or affect blood glucose homeostasis.
The mechanism appears to involve activation of beta-3 adrenergic receptor-related pathways in adipose tissue. Research by Ng and colleagues demonstrated that AOD-9604 mimics the way natural growth hormone regulates fat metabolism — it stimulates the breakdown of stored triglycerides in adipocytes while simultaneously blocking the formation of new fat. Importantly, studies have confirmed it does not compete with hGH for receptor binding, suggesting it acts through an independent signaling pathway.
More recent research has explored AOD-9604's effects on cartilage. Studies have shown it may promote proteoglycan and collagen synthesis in chondrocytes, opening potential applications in osteoarthritis research beyond its original anti-obesity focus.
Key Research Findings
- Ng et al. (2000) demonstrated AOD-9604 reduced body weight gain in obese Zucker rats without affecting IGF-1 levels or inducing glucose intolerance.
- Heffernan et al. (2001) showed the fragment stimulated lipolysis in both human and murine adipose tissue explants in a dose-dependent manner.
- Stier et al. (2012) found AOD-9604 promoted chondrocyte proliferation and extracellular matrix synthesis in cartilage tissue models.
- Ng & Borgeaud (2000) confirmed AOD-9604 does not bind the GH receptor and operates through an independent signal transduction mechanism.
References
Dosage in Research
Preclinical studies have used doses ranging from 50-500 mcg/kg in animal models. A Phase IIb human clinical trial studied oral doses of 1 mg, 5 mg, 10 mg, and 20 mg daily over 12 weeks.
Storage & Handling
Store lyophilized powder at -20C. Reconstituted solution should be refrigerated at 2-8C and used within 21 days. Protect from light.
Frequently Asked Questions
What is AOD-9604?
AOD-9604 is a synthetic peptide fragment corresponding to amino acids 176-191 of human growth hormone, with an added N-terminal tyrosine. It was designed to retain GH's fat metabolism effects without its growth or glucose-altering properties.
How does AOD-9604 differ from full-length growth hormone?
Unlike hGH, AOD-9604 does not bind the GH receptor, does not stimulate IGF-1 production, and does not affect blood glucose or insulin sensitivity. It specifically targets adipose tissue metabolism through a mechanism independent of classical GH signaling.
What is the research status of AOD-9604?
AOD-9604 has been studied in multiple preclinical models and progressed through Phase II clinical trials. While early obesity trials showed mixed results on primary endpoints, additional research areas including cartilage repair have since emerged.
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