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	221231-10-3;
3D model (JSmol)	Interactive image;
Abbreviations	YLRIVQCRSVEGSCGF
ChemSpider	57582224;
PubChem CID	71300630;
UNII	7UP768IP4M;
	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]

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.^[5] Development of AOD9604 was halted following insignificant efficacy in a later 24 week trial.^[5]

References

^ ^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.

[Heffernan-1] 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.

[:0-3] Calzada Limited press release (26 April 2013). "AOD9604 - Important Clarifications" (PDF).

[:1-4] Wallace, Natasha (2013-08-02). "Much ado about nothing: the peptide they say never worked". The Sydney Morning Herald. Retrieved 2024-08-14.

[auto-5] 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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