AOD9604
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Names | |
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IUPAC name
(2S)-2-[[2-[[(4R,7S,13S,16S,19S,22S,25R)-25-[[(2S)-5-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-5-oxopentanoyl]amino]-22-(3-carbamimidamidopropyl)-13-(2-carboxyethyl)-7,19-bis(hydroxymethyl)-6,9,12,15,18,21,24-heptaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carbonyl]amino]acetyl]amino]-3-phenylpropanoic acid
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Other names
H-Tyr-Leu-Arg-Ile-Val-Gln-Cys(1)-Arg-Ser-Val-Glu-Gly-Ser-Cys(1)-Gly-Phe-OH
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Identifiers | |
3D model (JSmol)
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Abbreviations | YLRIVQCRSVEGSCGF |
ChemSpider | |
PubChem CID
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UNII | |
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Properties | |
C78H123N23O23S2 | |
Molar mass | 1815.10 g·mol−1 |
Related compounds | |
Related compounds
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HGH Fragment 176–191 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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AOD9604 is an orally active, lipolytic peptide fragment of human growth hormone and derivative of the C-terminal domain of human growth hormone (HGH). It consists of HGH residues 176–191, with a tyrosine in place of the phenylalanine at the N-terminal end.[1] Initial human trials showed that it retains the lipolytic properties of human growth hormone without stimulating IGF-1 production.[2] However, later studies failed to demonstrate a sufficient lipolytic effect. Its development was terminated in 2007.[3][4]
Mechanism of action
[edit]AOD9604 appears to enhance lipolysis in mice by upregulating beta-3 adrenergic receptors. Beta-3 adrenergic receptor knockout mice are unresponsive to the lipolytic effects of AOD9604.[1]
Clinical data
[edit]In a 12 week randomised clinical trial, subjects receiving AOD9604 lost, on average, 1.8kg more than those receiving placebo.[5] Development of AOD9604 was halted following insignificant efficacy in a later 24 week trial.[5]
References
[edit]- ^ a b Heffernan, M.; Summers, R. J.; Thorburn, A.; Ogru, E.; Gianello, R.; Jiang, W. J.; Ng, F. M. (December 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. 142 (12): 5182–5189. doi:10.1210/endo.142.12.8522. ISSN 0013-7227. PMID 11713213.
- ^ Stier, Heike; Vos, Evert; Kenley, David (2013-04-23). "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans". Journal of Endocrinology and Metabolism. 3 (1–2): 7–15. doi:10.4021/jem157w. ISSN 1923-287X.
- ^ Calzada Limited press release (26 April 2013). "AOD9604 - Important Clarifications" (PDF).
- ^ Wallace, Natasha (2013-08-02). "Much ado about nothing: the peptide they say never worked". The Sydney Morning Herald. Retrieved 2024-08-14.
- ^ a b Valentino, Michael A.; Lin, Jieru E.; Waldman, Scott A. (June 2010). "Central and Peripheral Molecular Targets for Anti-Obesity Pharmacotherapy". Clinical Pharmacology and Therapeutics. 87 (6): 652–662. doi:10.1038/clpt.2010.57. ISSN 0009-9236. PMC 3136748. PMID 20445536.