AOD9604

AOD9604
Names
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
Other names
H-Tyr-Leu-Arg-Ile-Val-Gln-Cys(1)-Arg-Ser-Val-Glu-Gly-Ser-Cys(1)-Gly-Phe-OH
Identifiers
CAS Number
3D model (JSmol)
Abbreviations YLRIVQCRSVEGSCGF
ChemSpider
PubChem CID
UNII
InChI
  • InChI=1S/C78H123N23O23S2/c1-9-41(8)62(101-68(115)47(18-14-28-86-78(83)84)91-69(116)50(29-38(2)3)95-63(110)45(79)30-43-19-21-44(104)22-20-43)75(122)100-61(40(6)7)74(121)94-49(23-25-56(80)105)67(114)98-55-37-126-125-36-54(65(112)88-32-57(106)89-51(76(123)124)31-42-15-11-10-12-16-42)97-70(117)52(34-102)90-58(107)33-87-64(111)48(24-26-59(108)109)93-73(120)60(39(4)5)99-71(118)53(35-103)96-66(113)46(92-72(55)119)17-13-27-85-77(81)82/h10-12,15-16,19-22,38-41,45-55,60-62,102-104H,9,13-14,17-18,23-37,79H2,1-8H3,(H2,80,105)(H,87,111)(H,88,112)(H,89,106)(H,90,107)(H,91,116)(H,92,119)(H,93,120)(H,94,121)(H,95,110)(H,96,113)(H,97,117)(H,98,114)(H,99,118)(H,100,122)(H,101,115)(H,108,109)(H,123,124)(H4,81,82,85)(H4,83,84,86)/t41-,45-,46-,47-,48-,49-,50-,51-,52-,53-,54-,55-,60-,61-,62-/m0/s1
    Key: GVIYUKXRXPXMQM-BPXGDYAESA-N
SMILES
  • CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC1=O)CCCNC(=N)N)CO)C(C)C)CCC(=O)O)CO)C(=O)NCC(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3=CC=C(C=C3)O)N
Properties
Chemical formula
 C78H123N23O23S2
Molar mass 1815.10 g·mol−1
Related compounds
Related compounds
 HGH Fragment 176–191
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

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] Despite its limited efficacy, AOD9604 is still banned in athletes and tested for in competition.[5][6][7]

Mechanism of action

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

In a 12 week randomised clinical trial, subjects receiving AOD9604 lost, on average, 1.8kg more than those receiving placebo.[8] Development of AOD9604 was halted following insignificant efficacy in a later 24 week trial.[8]

References

  1. 1 2 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.
  2. ↑ 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.
  3. ↑ Calzada Limited press release (26 April 2013). "AOD9604 - Important Clarifications" (PDF).
  4. ↑ Wallace, Natasha (2013-08-02). "Much ado about nothing: the peptide they say never worked". The Sydney Morning Herald. Retrieved 2024-08-14.
  5. ↑ Thevis M, Thomas A, Schänzer W. Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions. Expert Rev Proteomics. 2014 Dec;11(6):663-73. doi:10.1586/14789450.2014.965159 PMID 25382550
  6. ↑ Cox HD, Smeal SJ, Hughes CM, Cox JE, Eichner D. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015 Jan;7(1):31-8. doi:10.1002/dta.1715 PMID 25208511
  7. ↑ Schänzer W, Thevis M. Human sports drug testing by mass spectrometry. Mass Spectrom Rev. 2017 Jan;36(1):16-46. doi:10.1002/mas.21479 PMID 26213263
  8. 1 2 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.
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