AOD-9604

AOD-9604 is a 16-amino-acid peptide fragment corresponding to the C-terminal lipolytic domain of human growth hormone (hGH amino acids 177–191), with a single tyrosine-to-alanine substitution at position 178 to enhance stability. This fragment was rationally designed based on the discovery that hGH's metabolic effects (lipolysis, insulin resistance) are mediated by a different receptor region than its anabolic effects (IGF-1 elevation, proliferation) — and that these functions can be pharmacologically separated.

The lipolytic mechanism of AOD-9604 involves activation of hormone-sensitive lipase (HSL) in adipose tissue via β-adrenergic receptor / PKA signaling, similar to catecholamine-induced lipolysis. Critically, AOD-9604 does not bind the full hGH receptor dimerization interface — it interacts with a distinct receptor region that triggers the β3-adrenergic cascade without activating the JAK2/STAT5 pathway responsible for IGF-1 synthesis. This functional selectivity means AOD-9604 stimulates fat breakdown without elevating blood glucose (no diabetogenic effect) and without inducing cell proliferation (no mitogenic risk).

AOD-9604 was developed by Metabolic Pharmaceuticals (Melbourne, Australia) in the early 2000s as an anti-obesity therapeutic. Phase 2b clinical trials in obese human subjects demonstrated statistically significant weight loss compared to placebo over 12 weeks, with no adverse effects on insulin sensitivity or glycemic control — differentiating it sharply from full-length hGH, which reliably induces insulin resistance at pharmacologic doses.

A Phase 3 trial for obesity was initiated but discontinued for commercial rather than safety reasons. The compound has since been repurposed in the research community as a tool for studying selective lipolysis — particularly valuable because it isolates the fat-burning component of the GH axis without the confounding hyperglycemic effects that complicate hGH research.

Store lyophilized AOD-9604 at -20°C, protected from light and moisture. Stability exceeds 18 months under these conditions. The peptide fragment is relatively stable — the tyrosine-to-alanine substitution at position 1 removes a major oxidative degradation pathway.

Reconstituted AOD-9604 should be stored at 2–8°C and used within 21 days. The solution should be clear and colorless. The 1–2× daily research protocol makes AOD-9604 one of the more administration-intensive research peptides; some protocols reconstitute larger multi-dose vials and aliquot into sterile single-use portions.