AOD-9604

AOD-9604 is a synthetic peptide corresponding to the C-terminal fragment (residues 176-191) of human growth hormone (hGH), with an additional tyrosine residue at the N-terminus for stability. This fragment was identified as the region of hGH responsible for its lipolytic (fat-reducing) activity, isolated from its growth-promoting and diabetogenic properties.

The peptide stimulates lipolysis (fat breakdown) and inhibits lipogenesis (fat synthesis) in adipose tissue through a mechanism that mimics the fat-metabolising action of natural growth hormone but does not interact with the GH receptor in a way that promotes growth or affects blood glucose. Specifically, AOD-9604 enhances beta-3 adrenergic receptor signalling in fat cells and stimulates hormone-sensitive lipase (HSL) activity, increasing the release of stored fatty acids for oxidation.

Critically, AOD-9604 does not affect IGF-1 levels, blood glucose, insulin sensitivity, or cellular proliferation — distinguishing it sharply from full-length growth hormone. This selectivity for fat metabolism without the anabolic or diabetogenic effects of hGH was the rationale for its development as a potential anti-obesity therapeutic.

AOD-9604 was developed in the 1990s by Professor Frank Ng and colleagues at Monash University in Melbourne, Australia. The research programme sought to isolate the fat-reducing activity of growth hormone from its other biological effects by identifying the minimal peptide fragment responsible for lipolysis.

The fragment corresponding to hGH residues 176-191 was identified as having potent lipolytic activity in adipose tissue without affecting IGF-1 or blood glucose. Metabolic Pharmaceuticals Limited subsequently licensed the compound and advanced it through Phase IIb clinical trials for obesity, which showed modest but statistically significant weight loss compared to placebo. Although the compound did not progress to Phase III for obesity, it received GRAS (Generally Recognized as Safe) status from the FDA in 2014 for use in food products, and it continues to be researched for fat metabolism, cartilage repair, and osteoarthritis applications.