Research library

AOD-9604 Research Overview: A Growth-Hormone C-Terminal Fragment and Its Lipolysis Study Record

Compiled by:: Peptide Pilots Scientific Content Team
Reviewed by:: Peptide Pilots Quality & Compliance review
Last revised:: 25 August 2026

What was AOD-9604 designed to do, and what did its published mechanistic and clinical studies find?

AOD-9604 is a synthetic 16-amino-acid peptide corresponding to a modified C-terminal fragment (residues 176-191) of human growth hormone, with an added N-terminal tyrosine. It was designed to isolate the lipolytic (fat-metabolising) region of growth hormone from the growth-promoting region associated with IGF-1 signalling. Cell and rodent studies report stimulation of lipolysis and inhibition of lipogenesis without the insulin-resistance or growth effects seen with full-length growth hormone. A multi-country phase IIb human obesity trial, sponsored by Metabolic Pharmaceuticals, reported weight loss that did not separate meaningfully from placebo, and clinical development for obesity was discontinued; the peptide has since been researched mainly in animal osteoarthritis and cartilage models.

This page is an educational literature summary for laboratory professionals. It is not medical advice, not a description of product performance, and it does not describe or endorse human or veterinary use. Materials referenced are supplied for controlled laboratory research only.

What is AOD-9604?

AOD-9604 is a 17-amino-acid synthetic peptide comprising the human growth hormone fragment 176-191 with an additional N-terminal tyrosine, retaining the region proposed to carry growth hormone's fat-metabolising activity while omitting sequences linked to IGF-1-mediated growth signalling.

In laboratory work it is studied in adipocyte lipolysis and lipogenesis assays, in rodent diet-induced obesity models, and, in a separate line of research, in cartilage and chondrocyte models relevant to osteoarthritis.

AOD-9604 names and identifiers

Also referred to as: hGH fragment 176-191; Anti-Obesity Drug 9604; tyrosine-hGH Frag 176-191

Sequence (one-letter)	YLRIVQCRSVEGSCGF
Residue count	17 amino acids (including added N-terminal tyrosine)
Molecular formula	C78H123N23O23S2
Average molecular weight	≈1815.1 g/mol
Parent sequence	Human growth hormone fragment, residues 176-191
CAS number	221231-10-3

AOD-9604 research background

Growth hormone's biological activity was known to separate anatomically: the N-terminal and central regions engage the GH receptor and drive IGF-1-dependent growth, while a C-terminal fragment was reported to retain lipolytic activity in earlier structure-activity work from the 1980s.

Metabolic Pharmaceuticals Ltd developed a stabilised, tyrosine-modified version of this fragment, designated AOD-9604, and pursued it through preclinical and clinical development as a candidate anti-obesity agent through the 2000s.

Following a phase IIb trial that did not demonstrate a clinically meaningful weight-loss advantage over placebo, obesity development was discontinued, and subsequent published research has focused on animal models of cartilage repair and osteoarthritis rather than weight management.

Proposed AOD-9604 mechanisms and pathways

Evidence is separated by study type. In-vitro and animal findings describe model systems and do not establish equivalent behaviour in humans.

AOD-9604 in-vitro and cell-based evidence

Isolated adipocyte studies report that AOD-9604 stimulates lipolysis (breakdown of stored triglycerides) and inhibits lipogenesis (fat synthesis), consistent with the proposed C-terminal growth-hormone activity.
Unlike full-length growth hormone, reported adipocyte and hepatocyte studies did not find AOD-9604 to stimulate IGF-1 production or to impair insulin-stimulated glucose uptake at the concentrations tested.
Chondrocyte and cartilage-explant studies, from a separate later research programme, report stimulation of cartilage matrix components, motivating musculoskeletal rather than metabolic follow-up work.

AOD-9604 animal-model evidence

Rodent studies report reduced fat mass and increased lipolysis with AOD-9604 administration in diet-induced and genetically obese models, without the organ growth changes associated with full-length growth hormone.
Reports in obese and normal mice found no significant effect on blood glucose or insulin sensitivity, a distinguishing feature from full-length growth hormone in the same assays.
Rodent and rabbit osteoarthritis and cartilage-injury models report reduced cartilage degeneration and structural improvement with AOD-9604 administration in the later musculoskeletal research programme.

Published AOD-9604 human-study evidence

A phase IIb randomised, placebo-controlled trial in overweight and obese participants reported weight loss in AOD-9604 groups that was statistically significant at some doses but not of a magnitude considered clinically meaningful relative to placebo, and the sponsor discontinued obesity development.
Earlier phase I/II studies reported that AOD-9604 was generally tolerated without the fluid retention, joint pain or insulin-resistance signals associated with full-length growth hormone.
No published human trial has assessed AOD-9604 for osteoarthritis or cartilage-repair endpoints; that research remains at the animal-model stage.

Published AOD-9604 studies

Selected published studies involving AOD-9604
Study	Model / type	Research question	Main observation	Citation
Heffernan et al., lipolytic fragment characterisation	Isolated rodent and human adipocytes	Does the hGH 176-191 fragment retain lipolytic activity separate from growth-promoting activity?	Reported stimulation of lipolysis and inhibition of lipogenesis without IGF-1 stimulation.	Endocrinology, 2001
Ng et al., obese mouse model	Diet-induced obese and lean mice	Does AOD-9604 reduce fat mass without growth-hormone-associated metabolic side effects?	Reported reduced fat mass with no significant change in blood glucose or insulin sensitivity.	Hormone Research, 2000
Metabolic Pharmaceuticals phase IIb obesity trial	Randomised, placebo-controlled human trial, overweight/obese adults	Does AOD-9604 produce clinically meaningful weight loss versus placebo?	Reported statistically significant but clinically modest weight-loss differences; obesity development was subsequently discontinued.	Sponsor and industry press disclosures; ASX/company announcements, 2007
Cartilage/osteoarthritis model studies	Rodent and rabbit joint-injury models	Does AOD-9604 affect cartilage degeneration in osteoarthritis models?	Reported reduced cartilage degradation and some structural improvement, motivating a separate musculoskeletal research line.	Indexed musculoskeletal-research literature, 2015

Limitations of the AOD-9604 evidence

The human obesity trial programme did not demonstrate a clinically meaningful effect, and the compound's clinical development for that indication was discontinued; this is the central fact that should accompany any citation of AOD-9604's lipolytic mechanism.
Much of the mechanistic literature originates from the peptide's original commercial developer, which limits independent verification of the earlier animal and cell findings.
Osteoarthritis and cartilage research is at an early animal-model stage, with no published human trial data for that indication.
Long-term human safety data are limited to the discontinued obesity trial programme and are not comprehensive by current standards.
As with other GH-derived fragments, batch purity and correct disulfide-bond formation are analytically important and not always reported in the older literature.

AOD-9604 laboratory characteristics

Handling and analytical information reported in the literature and in supplier documentation. Values apply to laboratory materials and are not directions for any other use.

Appearance	White to off-white lyophilised powder
Solubility	Soluble in water; dilute acetic acid may assist dissolution of some lots
Lyophilised storage	Commonly stored at −20 °C, desiccated and protected from light
Reconstituted handling	Refrigerated storage with short working periods is standard
Analytical testing	RP-HPLC purity and MS identity per lot; the sequence contains two cysteines forming an intramolecular disulfide bond that is checked by mass
Stability considerations	Correct disulfide-bond formation and avoidance of oxidative side reactions are the main documented handling concerns

Frequently asked AOD-9604 research questions

Is AOD-9604 the same as human growth hormone?

No. It is a short synthetic fragment (residues 176-191, with an added tyrosine) representing only the region of growth hormone proposed to carry lipolytic activity, not the receptor-binding regions responsible for IGF-1-mediated growth.

Did AOD-9604 succeed as an obesity treatment?

Its sponsor's phase IIb human trial reported weight-loss differences from placebo that were not considered clinically meaningful, and obesity development was discontinued.

What is AOD-9604 studied for now?

Published animal-model research has shifted toward cartilage and osteoarthritis endpoints; no human trial data exist yet for that indication.

Does AOD-9604 affect blood glucose like growth hormone does?

Reported rodent and early human studies did not find the insulin-resistance signal associated with full-length growth hormone, which was part of the original rationale for isolating this fragment.

AOD-9604 primary references

Heffernan M, Summers RJ, Thorburn A, et al. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. https://doi.org/10.1210/endo.142.12.8522
Ng FM, Sun J, Sharma L, et al. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research. https://doi.org/10.1159/000023550
Metabolic Pharmaceuticals Ltd (trial sponsor) (2007). Phase IIb clinical trial results of AOD9604 in obesity. Sponsor and industry press disclosures; ASX/company announcements. https://pubmed.ncbi.nlm.nih.gov/?term=AOD9604+obesity+trial
Various (2015). Effects of the growth hormone fragment AOD9604 on cartilage and osteoarthritis models. Indexed musculoskeletal-research literature. https://pubmed.ncbi.nlm.nih.gov/?term=AOD9604+cartilage+osteoarthritis

Authorship and revision

Compiled from primary literature and public databases. Every factual statement on this page is traceable to a listed reference. Compiled by Peptide Pilots Scientific Content Team; documentation and compliance review by Peptide Pilots Quality & Compliance review. First published 30 June 2026; last revised 25 August 2026. Pages are revised when the cited literature changes materially.