AOD-9604
Tyr-hGH(177-191), a 16-residue disulfide-bridged fragment of human growth hormone, freeze-dried in a sealed vial. Every lot is tested in the manufacturer’s own laboratory and has a certificate.
| Compound | AOD-9604 Tyr-hGH(177–191); lipolytic C-terminal fragment of human growth hormone |
|---|---|
| CAS number | 221231-10-3 |
| Molecular formula | C78H123N23O23S2 |
| Theoretical mass | 1815.1 Da |
| Sequence / structure | H-YLRIVQCRSVEGSCGF-OH (16 residues; Cys7–Cys14 disulfide; free N- and C-termini) |
| Label claim | 5 mg/vial |
| Form | Lyophilized (freeze-dried) powder or cake in a sealed glass vial with a rubber stopper and aluminium crimp cap |
| Storage, sealed | −20 °C, desiccated, dark |
| Purity specification | 99.0% or higher by RP-HPLC |
| Format | Lyophilized powder, sealed vial |
Sizes and lots
- 5 mg · 1 vial — $62.00 · lot PL-2609-006, certificate PL-26-00006
- 5 mg · Kit of 10 — $559.00 · lot PL-2609-006, certificate PL-26-00006
AOD-9604 is a 16-residue synthetic fragment of human growth hormone: the hormone's residues 177 to 191 with a tyrosine added at the N-terminus, closed into a loop by one disulfide between its two cysteines. This listing is a sealed vial holding 5 mg of the peptide as freeze-dried powder. Its literature comes mostly from one Australian research program and covers fat metabolism and insulin sensitivity in obese rodents, along with earlier work on what shorter C-terminal fragments of the hormone do.
AOD-9604 or fragment 176-191
AOD-9604 and HGH fragment 176-191 are often sold under each other's names, but they are different molecules. Both are sixteen residues long. The native fragment starts with phenylalanine, residue 176 of the hormone. AOD-9604 starts with tyrosine, followed by hormone residues 177 to 191; the AOD-9604 guide notes the tyrosine was added so the peptide could be radiolabelled in early tracer work. The certificate gives the sequence of this vial as H-YLRIVQCRSVEGSCGF-OH with a Cys7 to Cys14 disulfide, formula C78H123N23O23S2 and theoretical mass 1815.1 Da. Tyrosine carries one more oxygen atom than phenylalanine, so the native fragment comes in about 16 Da lighter, and the LC-MS identity result on the certificate settles which one is present. At 1815.1 Da, 5 mg is about 2.8 µmol, slightly less once the certificate's water content is allowed for. The same peptide is sold dissolved, in a preloaded AOD-9604 pen and an AOD-9604 nasal spray, and the HGH fragment 176-191 guide compares the two related peptides in detail.
What the research covers
Where the fragment came from
Interest in the C-terminal end of growth hormone goes back to the 1970s. Ng and Bornstein made synthetic peptides matching hormone residues 172-191, 176-191, 177-191, 178-191, 179-191 and 180-191 and tested them in normal rats1. The four longest caused a short-lived rise in blood glucose and a more sustained rise in plasma insulin, while 179-191 and 180-191 were inert1. Peptides containing the 178-191 sequence also reduced insulin sensitivity in insulin tolerance tests1. The authors concluded that activity needed both a minimum sequence and the correct physical configuration1. Two decades later, Ng and colleagues described AOD-9604 as a synthetic analogue of the hormone's lipolytic domain2.
Rodent studies of fat metabolism
In obese Zucker rats, a 19-day oral study found that AOD-9604 cut body weight gain by more than half compared with controls, and adipose tissue from treated animals showed higher lipolytic activity2. Euglycaemic clamps showed no adverse effect on insulin sensitivity, in contrast to chronic treatment with intact growth hormone2. Heffernan and colleagues followed with a 14-day study in obese ob/ob and lean mice using mini-osmotic pumps3. Growth hormone and AOD-9604 both reduced body weight gain in the obese mice, with higher fat oxidation and higher plasma glycerol, an index of lipolysis3. Unlike growth hormone, AOD-9604 did not cause hyperglycaemia or lower insulin secretion3.
A companion paper looked at the beta-3 adrenergic receptor4. Both compounds raised beta-3 receptor RNA in obese mice to lean levels, and their long-term effects on body weight and lipolysis failed to appear in beta-3 knockout mice; in an acute test, though, AOD-9604 still raised energy expenditure and fat oxidation in the knockouts4. The authors concluded that the lipolytic action was not mediated directly through that receptor4.
Receptor binding and structure
In cells transfected with the growth hormone receptor, AOD-9604 did not compete for receptor binding and did not induce cell proliferation, both of which growth hormone did3. What it binds instead was not identified in these papers. The structure may matter. Hogg reviewed evidence that disulfide bonds are not always inert, and that cleaving them controls the function of some secreted proteins and cell-surface receptors5, while Ng and Bornstein had already tied fragment activity to physical configuration1. None of the abstracts compared AOD-9604's closed ring with an open, reduced form, so the role of the disulfide is untested.
What is not established
Every finding above comes from rodents or cultured cells, and nearly all the AOD-9604 work from one research program. The developer also ran human studies, and Stier and colleagues published on the safety and tolerability of AOD-9604 in humans in 20136; this page does not summarise those trials, which used an oral tablet. The AOD-9604 guide covers the trials, the metabolism data and a later rabbit cartilage study. None of the studies used SCALE Performance material.
Frequently asked questions
Is AOD-9604 the same as HGH fragment 176-191?
No. Both are sixteen residues from the end of growth hormone, but AOD-9604 starts with tyrosine and the native fragment with phenylalanine. The certificate for this vial gives the sequence YLRIVQCRSVEGSCGF and a theoretical mass of 1815.1 Da, which LC-MS separates from the lighter native fragment.
What does the disulfide mean in practice?
The cysteines at positions 7 and 14 are joined in a ring, matching the bond between hormone residues 182 and 189. Reducing agents such as DTT or thiol buffers can open it, so keep them out of solutions unless an open form is what the experiment needs.
How should the vial be stored?
Sealed at −20 °C, desiccated and dark, as the certificate specifies. Let the vial warm to room temperature before opening so moisture does not condense on the powder. A reconstituted solution goes to 2 to 8 °C, protected from light, for no longer than your laboratory has established.
What has AOD-9604 been shown to do?
In obese rats and mice it reduced body weight gain and raised markers of lipolysis without the high blood glucose that growth hormone caused, and in cell tests it did not bind the growth hormone receptor. These are animal and cell findings, mostly from one program, and they show nothing about people.
References
- Ng FM, Bornstein J. Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. Am J Physiol. 1978;234(5):E521-6. DOI · PubMed
- Ng FM, Sun J, Sharma L, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274-8. DOI · PubMed
- Heffernan MA, Thorburn AW, Fam B, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001;25(10):1442-9. DOI · PubMed
- Heffernan M, Summers RJ, Thorburn A, et al. 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. 2001;142(12):5182-9. DOI · PubMed
- Hogg PJ. Disulfide bonds as switches for protein function. Trends Biochem Sci. 2003;28(4):210-4. DOI · PubMed
- Stier. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism. 2013. DOI
For laboratory research use only. Not for human or veterinary consumption. Products have not been evaluated by the U.S. Food and Drug Administration and are not intended to diagnose, treat, cure or prevent any disease.