AOD9604

AOD9604 (Anti-Obesity Drug 9604) is a synthetic peptide fragment corresponding to amino acids 177-191 of human growth hormone (hGH), with the addition of a tyrosine residue at the N-terminus. Developed at Monash University in Australia, AOD9604 was designed to isolate the lipolytic activity attributed to the C-terminal region of hGH while excluding the growth-promoting and diabetogenic effects associated with the full-length hormone. The peptide contains an internal disulfide bond between the two cysteine residues, which is critical for its three-dimensional conformation. AOD9604 has been studied in preclinical and early clinical settings, and it received GRAS (Generally Recognized as Safe) designation from the US FDA for use as a food ingredient. More recently, researchers have also investigated AOD9604 in the context of cartilage and joint biology.

AOD9604 has been investigated for its interaction with beta-3 adrenergic receptor pathways in adipose tissue. Researchers observed that the peptide stimulates lipolysis in preclinical adipocyte models through a mechanism distinct from full-length growth hormone signaling. Studies suggest that AOD9604 does not bind the growth hormone receptor and does not activate the JAK2/STAT5 pathway, which accounts for the absence of growth-promoting or IGF-1-elevating effects observed in animal studies. Instead, the peptide appears to modulate lipid metabolism through direct interaction with fat cell signaling cascades. In cartilage biology research, investigators have observed that AOD9604 is associated with proteoglycan synthesis in chondrocyte models, suggesting potential activity in extracellular matrix maintenance. The disulfide bridge between Cys₇ and Cys₁₄ is essential for maintaining the peptide’s bioactive conformation.

Lipolytic Activity

Heffernan et al. (2001) investigated AOD9604 in obese Zucker rats and observed that chronic administration was associated with reduced body weight gain without changes in IGF-1 levels or glucose tolerance, distinguishing its activity profile from that of full-length growth hormone [1].

Clinical Investigation

Stier et al. (2013) reported results from a randomized, placebo-controlled clinical study evaluating oral AOD9604 in overweight subjects. The study examined safety parameters and metabolic biomarkers over a 12-week treatment period [2].

Cartilage Biology

Krishnan et al. (2017) investigated AOD9604 in a preclinical model of joint pathology. Researchers observed that intra-articular administration was associated with changes in cartilage matrix composition and chondrocyte activity markers in the treated joints compared to controls [3].