AOD 9604

AOD 9604 is a synthetic hexadecapeptide corresponding to amino acids 176–191 of human growth hormone (hGH), with a tyrosine residue substituted at the N-terminus to confer metabolic stability. The "AOD" designation stands for "Anti-Obesity Drug," reflecting its origin as a drug development candidate by Metabolic Pharmaceuticals. The compound was engineered to isolate the lipolytic domain of hGH while eliminating the anabolic and diabetogenic properties associated with the full-length hormone.

Development as a pharmaceutical was formally discontinued in 2007 when a Phase IIb trial of 536 subjects failed to demonstrate statistically significant weight loss. Despite this regulatory failure, AOD 9604 has since been reclassified as a nutraceutical ingredient in some jurisdictions and remains widely used in research settings and compounding pharmacy formulations.

AOD 9604 exerts lipolytic effects through a mechanism distinct from full-length hGH. It does not bind the growth hormone receptor and does not stimulate IGF-1 production, which is why it lacks hGH's anabolic and insulin-sensitizing effects. Instead, it acts directly on adipocytes to stimulate lipolysis and inhibit lipogenesis, primarily through upregulation of beta-3 adrenergic receptor (beta-3 AR) expression in adipose tissue. Beta-3 AR activation promotes thermogenesis and fat oxidation by stimulating the production of cAMP in adipocytes, which activates hormone-sensitive lipase.

In beta-3 AR knockout mouse models, AOD9604 lost its long-term ability to reduce body weight and increase lipolysis, confirming the centrality of this receptor in the compound's metabolic mechanism. The peptide also appears to promote fat oxidation through direct stimulation of metabolic pathways independent of the pituitary-liver axis.