AOD 9604 is a synthetic 16-amino-acid peptide corresponding to residues 176-191 of the human growth hormone C-terminus, with an added N-terminal tyrosine. CAS 221231-10-3, molecular weight ~1815 g/mol. It isolates the lipolytic domain of hGH.

Research Guide

AOD 9604: The hGH 176-191 Lipolytic Fragment, Explained

Q: How does AOD 9604 differ from Growth Hormone?

Full-length hGH drives hepatic IGF-1 production and growth signalling. AOD 9604 is only the 176-191 fragment: published work reports lipolysis and reduced lipogenesis without measurable IGF-1 elevation and without the hyperglycaemic effects reported for hGH.

Q: What is the proposed mechanism of AOD 9604?

The fragment acts through beta-3 adrenergic receptor associated signalling in adipose tissue, increasing hormone-sensitive lipase activity and fatty-acid release while suppressing lipogenic enzyme expression.

Q: What clinical evidence exists for AOD 9604?

AOD 9604 reached Phase 2b with Metabolic Pharmaceuticals. A 12-week randomised study reported greater weight change than placebo in lower dose arms, but the larger Phase 2b trial did not meet its primary endpoint. It received FDA GRAS status as a food ingredient in 2014 and was never approved as a therapeutic.

Q: How is lyophilised AOD 9604 stored and reconstituted?

Store sealed vials at -20 C protected from light. Reconstitute with bacteriostatic water added slowly against the vial wall: 2 mL into a 5 mg vial gives 2.5 mg/mL. Swirl, do not shake. Store reconstituted solution at 2-8 C and use within 28 days.

AOD 9604 isolates a single functional domain of human growth hormone — the C-terminal 176–191 sequence responsible for fat metabolism — and leaves the rest of the molecule behind. This guide covers the fragment's proposed beta-3 adrenergic mechanism, the pharmacological reasons it behaves differently from full-length Growth Hormone, what the clinical program actually showed, and how the lyophilised compound is handled in the laboratory. For in-vitro research use only.

Bottom line: AOD 9604 (CAS 221231-10-3, MW ~1815 g/mol) is a 16-amino-acid synthetic fragment of human growth hormone spanning residues 176–191, with an N-terminal tyrosine added for stability. In published work it stimulates lipolysis and suppresses lipogenesis in adipose tissue through beta-3 adrenergic-associated signalling, while — unlike full-length hGH — producing no measurable rise in IGF-1 and no meaningful effect on glucose tolerance. Its clinical program reached Phase 2b without meeting the primary weight endpoint; it later received FDA GRAS status as a food ingredient but was never approved as a therapeutic. WADA-prohibited (S0). PeptidesDirect supplies AOD 9604 strictly for in-vitro laboratory research.

What the Fragment Is

Human growth hormone is a 191-amino-acid single-chain polypeptide. Structure–function work in the 1990s at Monash University mapped its metabolic activity to a discrete C-terminal region: residues 176–191. Synthesising that region alone, with a tyrosine added at the N-terminus, produced AOD 9604 — a peptide roughly one twelfth the mass of hGH that retains the fat-metabolising signal and discards the growth-signalling one.

Property	AOD 9604
Sequence origin	hGH residues 176–191 + N-terminal Tyr
Length	16 amino acids
CAS	221231-10-3
Molecular weight	~1815 g/mol
Form supplied	Lyophilised powder, 5 mg vial
Developer	Metabolic Pharmaceuticals (Australia)

Proposed Lipolytic Mechanism

In adipocyte models the fragment increases the rate of triglyceride breakdown and reduces the expression of lipogenic enzymes. The effect is closely associated with beta-3 adrenergic receptor (β3-AR) signalling: β3-AR expression rises in treated adipose tissue, and the lipolytic response is attenuated in some β3-AR-deficient models — though not abolished in all of them, which is why the literature stops short of calling the pathway exclusively β3-AR-mediated.

Lipolysis ↑

Increased hormone-sensitive lipase activity and free fatty-acid release from adipocytes, reported in rodent and in-vitro fat-cell models.

Lipogenesis ↓

Reduced expression of enzymes governing fatty-acid synthesis and triglyceride re-esterification, limiting re-accumulation.

🧬 AOD 9604 vs Full-Length Growth Hormone

Attribute	hGH (191 aa)	AOD 9604 (16 aa)
Lipolytic activity	Yes	Yes — retained domain
IGF-1 induction	Marked hepatic increase	Not reported at studied exposures
Tissue / skeletal growth signalling	Yes, via GH receptor + IGF-1	Not observed
Effect on glucose tolerance	Can reduce insulin sensitivity	No clinically meaningful effect reported
Cartilage / chondrocyte proliferation	Yes	Not observed
Typical research framing	Endocrine hormone replacement models	Isolated adipose-metabolism models

The practical significance for researchers: AOD 9604 allows adipose-tissue lipolysis to be studied without the confounding systemic IGF-1 axis activation that accompanies full-length hGH administration.

What the Evidence Actually Shows

Preclinical: consistent reductions in adipose mass in obese rodent models, with no change in IGF-1 or growth parameters.
Phase 2 (12 weeks): oral dosing arms reported greater mean weight change than placebo, with the lower dose arms performing best — a non-monotonic dose response.
Phase 2b: the larger confirmatory study did not separate from placebo on its primary endpoint, and therapeutic development was discontinued.
Safety signal: across trials the fragment was well tolerated, with no IGF-1 elevation and no significant glycaemic effect reported.
Regulatory: FDA GRAS notification accepted in 2014 for use as a food ingredient in the US; never approved as a drug in any jurisdiction.

Readers should consult the primary literature (Heffernan et al., Endocrinology 2001; Ng et al., Hormone Research 2000; Stier et al., Journal of Obesity 2013) rather than relying on secondary summaries.

Laboratory Handling & Reconstitution

The 5 mg lyophilised vial reconstitutes to 2.5 mg/mL with 2 mL of bacteriostatic water, or 5 mg/mL with 1 mL. Add diluent slowly down the vial wall and swirl until fully dissolved; never shake, as mechanical shear degrades short peptide chains.

Sealed lyophilised vials: −20 °C, protected from light.
Reconstituted solution: 2–8 °C, use within 28 days.
Avoid repeated freeze–thaw cycles; aliquot for long studies.
Use low-dead-space syringes to preserve microgram-level accuracy.

Full technique is covered in the peptide reconstitution guide and the bacteriostatic water guide.

Frequently Asked Questions

What is AOD 9604?

AOD 9604 (Anti-Obesity Drug 9604) is a synthetic 16-amino-acid peptide corresponding to residues 176–191 of the human growth hormone (hGH) C-terminus, with an added tyrosine at the N-terminus. CAS 221231-10-3, molecular weight ~1815 g/mol. It isolates the lipolytic domain of hGH without the rest of the hormone's structure.

How does AOD 9604 differ from Growth Hormone?

Full-length hGH (191 amino acids) binds the growth hormone receptor and drives hepatic IGF-1 production, which mediates growth, tissue proliferation, and much of hGH's effect on insulin sensitivity. AOD 9604 is only the 176–191 fragment: in published work it stimulates lipolysis and inhibits lipogenesis without measurably raising IGF-1, without binding the GH receptor in the classical growth-signalling manner, and without the hyperglycaemic effects reported for hGH.

What is the proposed mechanism of AOD 9604?

The fragment appears to act through beta-3 adrenergic receptor (β3-AR) signalling in adipose tissue, increasing hormone-sensitive lipase activity and fatty-acid release while suppressing lipogenic enzyme expression. Some rodent data also point to β3-AR-independent effects on adipocyte metabolism, so the pathway is best described as β3-AR-associated rather than exclusively β3-AR-mediated.

Does AOD 9604 raise IGF-1 or blood glucose?

Published preclinical and early clinical work reports no significant increase in IGF-1 and no clinically meaningful effect on glucose tolerance or insulin sensitivity at studied exposures — the principal reason the fragment was investigated as an anti-obesity candidate rather than a GH analogue.

What clinical evidence exists for AOD 9604?

AOD 9604 was developed by Metabolic Pharmaceuticals and reached Phase 2b. A 12-week randomised placebo-controlled study in obese participants reported greater weight change than placebo at lower dose arms, but the larger Phase 2b trial did not meet its primary endpoint versus placebo. The compound was subsequently granted FDA GRAS status as a food ingredient in the United States in 2014, but it has never been approved as a therapeutic drug.

What dosing was used in AOD 9604 research?

Human studies used oral and subcutaneous routes at daily doses in the 250 µg–1 mg range; the frequently cited Phase 2 arms were 1 mg, 5 mg, 10 mg and 20 mg orally, once daily. Laboratory protocols using the lyophilised 5 mg vial commonly reconstitute with bacteriostatic water for in-vitro work. All figures here describe published study designs, not use recommendations.

How is lyophilised AOD 9604 stored and reconstituted?

Store the sealed lyophilised vial at −20 °C, protected from light. Reconstitute with bacteriostatic water (0.9% benzyl alcohol) added slowly against the vial wall — 2 mL into a 5 mg vial gives a 2.5 mg/mL working solution. Swirl, do not shake. Keep the reconstituted solution at 2–8 °C and use within 28 days; avoid repeated freeze–thaw cycles.

Is AOD 9604 a banned substance in sport?

Yes. AOD 9604 is listed by WADA under S0 (non-approved substances) and is prohibited at all times in competitive sport. PeptidesDirect supplies it strictly as a research chemical for in-vitro laboratory use.

For research use only. AOD 9604 sold by PeptidesDirect is supplied strictly for in-vitro laboratory research conducted by qualified professionals. It is not approved as a therapeutic in any jurisdiction, is prohibited in competitive sport under WADA class S0, and is not intended for human or veterinary consumption.

AOD 9604 — Research Compound

5 mg vial · ≥98% HPLC purity · CAS 221231-10-3

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