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FIELD NOTES / AOD 9604: THE HGH FRAGMENT 176-191 EXPLAINED

AOD 9604: The hGH Fragment 176-191 Explained

AOD 9604 explained: a modified C-terminal fragment of human growth hormone. Sequence, identity data, research history and regulatory context.

AOD9604 5mg - Compound Cave research material

AOD 9604 is a synthetic peptide based on the C-terminal region of human growth hormone (hGH), corresponding to residues 177-191 with an added N-terminal tyrosine. It is often described as a modified hGH fragment 176-191. The compound was developed in Australia in the 1990s and has been studied mainly in rodent models of lipid metabolism. This article explains where AOD 9604 came from, how it is built and what the published literature examined.

For laboratory research use only. Not for human or veterinary use. See our research use only policy.

At a glance: AOD 9604 identity

  • Name: AOD 9604
  • Synonyms: AOD9604, Tyr-hGH(177-191), modified hGH fragment 176-191, anti-obesity drug 9604 (development code)
  • Sequence: Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (disulfide Cys7-Cys14)
  • Molecular formula: C78H123N23O23S2
  • Molecular weight: 1815.1 g/mol
  • CAS number: 221231-10-3
  • Form: Lyophilised powder
  • Purity: >99% (HPLC)
  • Storage: 2-8°C, dark, upright, do not freeze. Keep sealed until use.

From growth hormone to a fragment

Human growth hormone is a 191-amino-acid protein with two disulfide bridges. In the 1980s and 1990s, researchers at Monash University in Melbourne, including Frank Ng and colleagues, investigated whether different regions of the hormone carried distinct activities. Their work focused on the C-terminal segment, and they reported that synthetic peptides from this region affected lipid metabolism in rodent adipose tissue, while appearing not to share the growth-related activity of the full hormone in the models tested.

AOD 9604 was the optimised peptide from this programme. It covers hGH residues 177-191 and carries an extra tyrosine at the N-terminus, which is why it is sometimes described as "176-191" even though residue 176 of native hGH is not tyrosine. The extra tyrosine was introduced during optimisation of the peptide, so the term "modified fragment" is the more accurate description.

Structure

AOD 9604 is a 16-residue peptide containing two cysteines at positions 7 and 14, which form an intramolecular disulfide bond. This creates a small cyclic loop, mirroring the disulfide between Cys182 and Cys189 in native hGH. Points of note for laboratory work:

  • The disulfide. The cyclic form is the intended structure. Reducing conditions will break the bond, and analytical methods should distinguish the oxidised (cyclic) form from the reduced linear form, which differ in mass by 2 Da.
  • Charge. Two arginines and one glutamate give the peptide a modest net positive charge at neutral pH.
  • Aromatic residues. The N-terminal tyrosine and C-terminal phenylalanine give UV absorbance useful in HPLC detection.

Identity is confirmed by mass spectrometry against the calculated molecular weight of 1815.1 g/mol. Our guide on how to read a peptide certificate of analysis explains how mass and HPLC data are interpreted.

What the research investigated

Rodent studies

Published work from the Monash group and the developing company examined AOD 9604 in obese mouse and rat models. A 2001 paper by Heffernan and colleagues in Endocrinology compared hGH with AOD 9604 in obese mice and in beta-3 adrenergic receptor knockout mice, reporting changes in lipid metabolism markers and examining whether the beta-3 adrenergic receptor was involved. Earlier work by Ng and colleagues (Hormone Research, 2000) reported effects on lipolysis and lipogenesis in rodent adipose tissue. The authors also reported that the fragment did not alter markers such as IGF-1 in the way full hGH did in those models.

Receptor question

A recurring point in the literature is that AOD 9604 was reported not to bind the growth hormone receptor in a meaningful way in the assays used. The mechanism proposed for its activity in rodent fat tissue has therefore been discussed as separate from classical GH receptor signalling, and it has not been fully defined.

Clinical development

AOD 9604 entered human clinical trials as a potential obesity medicine in the early 2000s. The development programme was discontinued after later-stage trials, and AOD 9604 is not an approved medicine in the UK. The material supplied by Compound Cave is a research chemical, not a medicine.

Related compounds and context

AOD 9604 is sometimes confused with other growth hormone-related peptides. It is not a growth hormone secretagogue and is chemically unrelated to GHRH analogues such as tesamorelin, or to ghrelin-receptor agonists such as ipamorelin. For that area of research, see tesamorelin, the GHRH analogue and CJC-1295 and ipamorelin.

Within this metabolic research cluster, AOD 9604 sits apart from the mitochondrial compounds. MOTS-c, the mitochondrial-derived peptide is our pillar guide to the cluster and links to the other compounds covered, including 5-Amino-1MQ and NAD+.

Handling and storage

AOD 9604 is supplied as a lyophilised powder. Store sealed vials at 2-8°C, in the dark and upright, and do not freeze. Allow vials to reach room temperature before opening to prevent condensation, and keep them sealed when not in use. Because the disulfide bond is important to the intended structure, avoid exposing the material to reducing agents unless that is part of the experimental design. See how to store lyophilised peptides for general guidance.

View AOD 9604 in the catalogue.

Frequently asked questions

Is AOD 9604 the same as hGH fragment 176-191?

They are closely related. AOD 9604 corresponds to hGH residues 177-191 with an additional tyrosine at the N-terminus, so it is often called a modified 176-191 fragment. Some suppliers use the names interchangeably, but the sequence should always be checked.

Does AOD 9604 contain a disulfide bond?

Yes. The cysteines at positions 7 and 14 form an intramolecular disulfide bond, mirroring the Cys182-Cys189 bridge in native growth hormone.

Is AOD 9604 a growth hormone secretagogue?

No. It is a fragment of the hormone itself, not a compound that acts on the pituitary. It is unrelated to GHRH analogues and ghrelin-receptor agonists.

Is AOD 9604 an approved medicine?

No. Its clinical development as an obesity medicine was discontinued, and it is not approved as a medicine in the UK. Compound Cave supplies it for laboratory research use only.

What is the CAS number of AOD 9604?

The CAS number is 221231-10-3. The molecular formula is C78H123N23O23S2 and the molecular weight is 1815.1 g/mol.

References

  • Heffernan M, Summers RJ, Thorburn A, et al. (2001). Endocrinology, 142(12), 5182-5189. hGH and AOD9604 in obese and beta-3 adrenergic receptor knockout mice.
  • Ng FM, Sun J, Sharma L, et al. (2000). Hormone Research, 53(6), 274-278. Metabolic studies of a synthetic C-terminal hGH fragment in rodents.
  • Heffernan MA, Jiang WJ, Thorburn AW, Ng FM. (2000). American Journal of Physiology Endocrinology and Metabolism, 279(3), E501-E507. hGH fragment and adipose tissue metabolism in obese mice.

AOD 9604 offers a defined, disulfide-bridged peptide for studying the C-terminal region of growth hormone, with a literature concentrated in rodent models from the late 1990s and early 2000s.

For laboratory research use only. Not for human or veterinary use. See our research use only policy.