AOD-9604

What Is AOD-9604?

AOD-9604 is a 16-amino-acid synthetic fragment of human growth hormone, corresponding to residues 177 to 191 of the hGH C-terminus with an added N-terminal tyrosine. The tyrosine distinguishes it from native HGH Fragment 176-191 and was introduced by Metabolic Pharmaceuticals to improve stability and permit radiolabelling during development. The compound was designed to reproduce the lipolytic and anti-lipogenic actions of growth hormone without engaging the growth, IGF-1, or insulin-resistance pathways.

In rodent models, AOD-9604 stimulates lipolysis in adipocytes and increases beta-3 adrenergic receptor expression. The human data did not replicate this: the fragment binds a high-affinity but uncharacterised adipose receptor (not GH-R and not beta-3-AR directly), and the in-vivo lipolytic signal in humans proved far weaker than the rodent work predicted. The Australian Phase 2b obesity trial failed its primary endpoint at every tested dose. The safety side of the design brief held up, with no growth, IGF-1, or insulin effects and a clean adverse-event profile across roughly 900 trial participants. AOD-9604 has since been studied in cartilage-repair and osteoarthritis models, where the mechanism under investigation is distinct from its original metabolic rationale.