AOD-9604

AOD-9604 (Advanced Obesity Drug-9604) is a synthetic 16-amino-acid peptide corresponding to the C-terminal fragment of human growth hormone (hGH), specifically amino acids 176-191, with the addition of a tyrosine residue at the C-terminus for stability. Its sequence is Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe-Tyr, with a disulfide bond between Cys182 and Cys189. The molecular weight is approximately 1,815 Da. CAS number: 221231-10-3. Unlike full-length hGH (191 amino acids, 22 kDa), AOD-9604 isolates only the lipolytic domain, excluding the regions responsible for growth, IGF-1 stimulation, and diabetogenic effects.

AOD-9604 mimics the mechanism by which natural growth hormone regulates fat metabolism. It activates the beta-3 adrenergic receptor pathway in adipocytes, stimulating hormone-sensitive lipase (HSL) activity and triggering the release of stored triglycerides from fat cells (lipolysis). Simultaneously, it inhibits lipogenesis by downregulating key lipogenic enzymes including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in adipose tissue. The critical distinction from full hGH is that AOD-9604 does not bind the growth hormone receptor (GHR) in a way that activates the JAK2-STAT5 signaling cascade responsible for IGF-1 production, longitudinal bone growth, or insulin resistance. This means it targets fat metabolism through a distinct, non-GHR-dependent pathway.

Multiple clinical studies have evaluated AOD-9604. A Phase 2b randomized, double-blind, placebo-controlled trial conducted by Metabolic Pharmaceuticals enrolled 300 obese subjects (BMI 35-45) and demonstrated statistically significant reductions in body fat over 12 weeks at the 1mg daily dose compared to placebo, without changes in IGF-1 levels, glucose tolerance, or other growth hormone-related parameters. An earlier Phase 2a trial (N=53) published in the Journal of Clinical Endocrinology and Metabolism showed dose-dependent fat loss over 4 weeks. Animal studies in obese Zucker rats demonstrated that AOD-9604 reduced body fat by up to 50% without affecting lean mass, food intake, or growth.

AOD-9604 has a relatively short plasma half-life of approximately 30-45 minutes following subcutaneous injection, reflecting its small peptide size and lack of albumin-binding modifications. Peak plasma concentration is achieved within 15-30 minutes. Due to its short half-life, AOD-9604 is typically administered daily in research settings. The peptide is rapidly cleared by renal filtration and proteolytic degradation. Its mechanism of action involves triggering intracellular signaling cascades that persist beyond its plasma presence, so the biological effect duration exceeds the circulating half-life.

Lyophilized AOD-9604 should be stored at -20C before reconstitution. Reconstitute with bacteriostatic water (0.9% benzyl alcohol) by adding water slowly along the vial wall and gently swirling. Do not shake or vortex, as this can damage the disulfide bond critical to the peptide's tertiary structure. Reconstituted solution should be stored at 2-8C and used within 21 days. AOD-9604 is stable at pH 5.0-7.0 in aqueous solution. The disulfide bridge between Cys182 and Cys189 is important for activity; reducing conditions or excessive heat will inactivate the peptide.

AOD-9604 is studied in research on fat metabolism, obesity, adipocyte biology, cartilage repair, and osteoarthritis. Interestingly, AOD-9604 has shown chondroprotective properties in preclinical models, stimulating proteoglycan synthesis in articular cartilage. This has led to research into its potential applications beyond fat metabolism, including joint health and cartilage regeneration. It is also studied in combination protocols with GLP-1 agonists and other metabolic peptides.

AOD-9604 received FDA GRAS (Generally Recognized As Safe) status in 2007 (GRN 000620), making it one of the few peptides with this designation. Across all clinical trials, no serious adverse events were attributed to AOD-9604. Specifically, there were no changes in glucose homeostasis, no elevation of IGF-1 levels, no effects on bone growth plates, no anti-AOD-9604 antibody formation, and no hematological or biochemical abnormalities. Injection site reactions were mild and comparable to placebo. The GRAS determination further confirmed its favorable safety profile based on extensive toxicology data.