Research Peptide · For laboratory research use only

AOD9604

Also known as Anti-Obesity Drug 9604, Tyr-hGH Frag 177-191

Formula
C78H123N23O23S2
CAS
221231-10-3

Overview

AOD9604 is a synthetic 16-residue peptide corresponding to the C-terminal region of human growth hormone (residues 177 to 191) with an added N-terminal tyrosine, and is also described as Tyr-hGH(177-191). Earlier work had shown that the synthetic hGH 177-191 fragment had antilipogenic activity in rat adipose tissue identical to that of the intact hormone, and that a related synthetic fragment had lipolytic and antilipogenic activity in rodent models1,2.

Published research is preclinical and centres on lipid metabolism in rodent models of obesity, including obese Zucker rats, ob/ob mice and beta(3)-adrenergic receptor knockout mice3,4,5. A separate study examined the peptide in a rabbit model of collagenase-induced knee osteoarthritis6.

Mechanism of action

As described in the research literature

As described in the research literature, the C-terminal domain of growth hormone was proposed to carry the hormone's antilipogenic activity: the hGH 177-191 fragment reduced lipogenesis in rat epididymal fat pads without a significant lipolytic effect in that assay1. A related fragment, AOD-9401, was reported to reduce lipogenic and increase lipolytic activity in isolated adipose tissue from obese rodents and in human adipose tissue in vitro2.

For AOD9604 itself, in vitro work in cells transfected with the hGH receptor reported that the peptide did not compete for receptor binding and did not induce cell proliferation, unlike intact hGH4. In obese mice, both hGH and AOD9604 increased expression of beta(3)-adrenergic receptor RNA in adipose tissue; however, the effect on energy expenditure and fat oxidation was still observed acutely in beta(3)-AR knockout mice, and the authors concluded that the lipolytic actions are not mediated directly through this receptor5.

Research areas

What published studies have examined

Lipid metabolism in rodent obesity models

Studies in obese Zucker rats examined body weight gain, adipose tissue lipolytic activity and insulin sensitivity by euglycaemic clamp3. Work in ob/ob and lean C57BL/6J mice measured body weight, caloric intake, resting energy expenditure, fat and glucose oxidation, and plasma glucose, insulin and glycerol, comparing AOD9604 with intact hGH4.

Sources [3] [4]

Growth hormone receptor and adrenergic signalling

Receptor binding and proliferation assays in hGH receptor-transfected BaF-BO3 cells were used to test whether AOD9604 acts through the growth hormone receptor4. Studies in obese and beta(3)-AR knockout mice examined beta(3)-adrenergic receptor expression and its contribution to the lipolytic response5.

Sources [4] [5]

Origin of the C-terminal fragment

Earlier work characterised the antilipogenic activity of the synthetic hGH 177-191 sequence in rat fat pads1, and the lipolytic and antilipogenic activity of the related fragment AOD-9401 in ob/ob mice and in isolated rodent and human adipose tissue2.

Sources [1] [2]

Cartilage model

A study in New Zealand white rabbits with collagenase-induced knee osteoarthritis compared AOD9604, hyaluronic acid, their combination and saline, assessing cartilage by gross morphological and histopathological scoring and recording the duration of lameness6.

Sources [6]

Specifications

Sequence
Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (YLRIVQCRSVEGSCGF), with a disulfide bridge between the two cysteines
Molecular formula
C78H123N23O23S2
Molecular weight
1815.1 g/mol
CAS number
221231-10-3
Form
White to off-white lyophilised powder in a sealed vial (5 mg or 10 mg)
Storage
Store lyophilised powder at -20 °C, protected from light and moisture. Once reconstituted, keep refrigerated at 2 to 8 °C and protect from light.
Solubility and reconstitution
Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and swirl gently until clear; do not shake.

References

  1. 1

    Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone.

    Wu Z, Ng FM Biochemistry and Molecular Biology International, 1993.

  2. 2

    Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism.

    Heffernan MA, Jiang WJ, Thorburn AW, et al. American Journal of Physiology. Endocrinology and Metabolism, 2000.

  3. 3

    Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone.

    Ng FM, Sun J, Sharma L, et al. Hormone Research, 2000.

  4. 4

    Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.

    Heffernan MA, Thorburn AW, Fam B, et al. International Journal of Obesity and Related Metabolic Disorders, 2001.

  5. 5

    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.

    Heffernan M, Summers RJ, Thorburn A, et al. Endocrinology, 2001.

  6. 6

    Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.

    Kwon DR, Park GY Annals of Clinical and Laboratory Science, 2015.

This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.

RUO. For research purposes only. Not for human consumption. Not for veterinary use.

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