AOD-9604 is a synthetic peptide built from the C-terminal end of human growth hormone (hGH), specifically the sequence spanning residues 177 to 191, with an added tyrosine joined at the N-terminus to complete a 16-amino-acid chain researchers refer to as hGH fragment 176-191. It was designed at Monash University in Australia in the early 1990s to let researchers study this single structural domain of hGH in isolation from the rest of the hormone. It is not an approved drug and is supplied here strictly as a research chemical for laboratory use.
AOD-9604 at a glance
| Attribute | Detail |
|---|---|
| Common name | AOD-9604 (also written AOD9604) |
| Classification | Synthetic peptide, modified C-terminal fragment of human growth hormone |
| Sequence | 16 amino acids: an added tyrosine joined to the native hGH sequence spanning residues 177-191 (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Val-Ser-Glu-Gly-Ser-Cys-Gly-Phe) |
| Structural note | Contains two cysteine residues, as in native hGH, positioned to allow an intramolecular disulfide bond (Wu and Ng, 1993) |
| Origin | Designed and first characterized at Monash University, Australia (Wu and Ng, 1993) |
| What studies examine | Lipid metabolism in rodent models, hGH-receptor binding, cell proliferation assays, analytical detection methods |
| FDA drug status | Not an FDA-approved drug; reviewed only as a nominated (later withdrawn) compounding bulk substance (FDA) |
| Form supplied | Lyophilized powder, research use only |
What is AOD-9604 and where does its structure come from?
Human growth hormone is a 191-amino-acid protein. In the early 1990s, researchers at Monash University set out to determine which region of that protein was responsible for its antilipogenic activity, meaning its effect on lipid synthesis in fat tissue, as distinct from its growth-promoting and insulin-antagonizing effects. Wu and Ng synthesized the C-terminal sequence of hGH, residues 177 through 191, and reported that this isolated fragment reproduced the antilipogenic activity of the intact hormone in treated rats, while no significant lipolytic effect was detected by glycerol release from fat pads in that same study (Wu and Ng, 1993). A tyrosine residue was subsequently joined to the N-terminus of that 15-residue fragment to improve stability and enable radiolabeling and immunoassay detection, producing the 16-amino-acid analog named AOD-9604, short for Anti-Obesity Drug 9604 (Cox et al., 2015). The resulting sequence retains the two cysteine residues present in the native hGH backbone at that position, arranged so they can form an internal disulfide bond, the same structural feature found in the corresponding region of full-length hGH (Wu and Ng, 1993). Our AOD-9604 research library monograph collects this structural and study data in one reference page.
What is the Monash University research history behind AOD-9604?
The compound traces to a research program run by Frank M. Ng and colleagues at Monash University, who spent the 1990s mapping which structural domains of hGH controlled which of the hormone's separate activities. After the 1993 fragment-mapping paper, the same group reported that chronic treatment with the hGH 177-191 peptide reduced cumulative body weight gain and adipose tissue mass in obese (ob/ob) mice relative to untreated controls, and inhibited lipogenesis in adipose tissue in that model (Natera et al., 1994). This body of work was later licensed and developed further by an Australian pharmaceutical company under the name AOD-9604, which took the compound through additional preclinical work and into human clinical study before its development program ended without the compound reaching market as an approved drug. Independent of that commercial history, the peptide has continued to appear in the academic literature, including analytical chemistry papers on how to detect it (Cox et al., 2015; Orlovius et al., 2013).
What did preclinical studies examine?
Follow-on preclinical work moved from the original mouse and rat fragment studies into other rodent models. Ng and colleagues studied AOD-9604 in obese Zucker rats, reporting that daily oral dosing over 19 days reduced body weight gain by more than half relative to control animals and increased lipolytic activity measured in adipose tissue, with no adverse effect on insulin sensitivity as assessed by euglycemic clamp, in contrast to what the same group observed with intact hGH treatment (Ng et al., 2000). A separate study compared chronic treatment with intact hGH against AOD-9604 in obese and lean mice, measuring body weight, caloric intake, resting energy expenditure, and substrate oxidation rates, and used in vitro receptor-binding assays in cells transfected with the hGH receptor to test whether AOD-9604 engages that receptor the way intact hGH does (Heffernan et al., 2001). These are cell-line and rodent findings; none of the cited studies describe outcomes in unmedicated humans, and none of this preclinical work constitutes evidence of an effect in people.
What did clinical development examine, and did AOD-9604 receive FDA approval?
AOD-9604 was carried into human clinical study as part of a pharmaceutical development program in the 2000s that examined safety, tolerability, and metabolic markers such as IGF-1 levels and glucose handling in study participants. That development program did not result in an FDA-approved drug, and AOD-9604 has never been approved by the FDA for any indication, in contrast to hGH-pathway drugs that are FDA-approved, such as tesamorelin, which carries its own approved label and prescribing information.
Separately from the drug-approval pathway, FDA's Pharmacy Compounding Advisory Committee evaluated AOD-9604, in both free-base and acetate forms, as a nominee for the Section 503A bulk drug substances list, the list of substances compounding pharmacies may use to prepare patient prescriptions. FDA's published summary states that AOD-9604 was nominated and subsequently withdrawn from that review, and that "FDA has identified no, or only limited, safety-related information" on the substance, that compounded drugs containing AOD-9604 "may pose significant risk for immunogenicity for certain routes of administration" along with complexities in characterizing peptide-related impurities, and that serious adverse events have been reported in association with AOD-9604 though causality has not been established (FDA). None of this FDA review process constitutes drug approval, and it does not apply to material sold and labeled for research use only.
How does AOD-9604 differ from full-length growth hormone?
The receptor-binding work from the original Monash research program is the clearest point of comparison. Using cells transfected with the hGH receptor, Heffernan and colleagues reported that AOD-9604 did not compete for the hGH receptor and did not induce the receptor-mediated cell proliferation that intact hGH produced in the same assay system (Heffernan et al., 2001). Because AOD-9604 is only the C-terminal domain of the hormone plus an added tyrosine, it lacks the receptor-binding surfaces distributed across the rest of the 191-residue hGH molecule. That distinction is also why analytical chemists treat AOD-9604 as a separate detection target from intact hGH: it requires its own extraction and mass-spectrometry method to identify in a sample rather than being picked up by an hGH assay (Cox et al., 2015).
How does AOD-9604 differ from growth hormone secretagogues?
AOD-9604 and growth hormone secretagogues are studied for entirely different mechanisms and should not be treated as interchangeable in a protocol. AOD-9604 is a direct structural fragment of hGH itself, synthesized to reproduce one domain of the hormone. Secretagogues such as ipamorelin, sermorelin, and CJC-1295 are separate peptide classes that act on ghrelin or growth-hormone-releasing-hormone receptors at the pituitary to stimulate the body's own endogenous hGH release, and they do not share AOD-9604's C-terminal hGH sequence. Our overview of growth hormone secretagogues in research covers how ipamorelin, CJC-1295, sermorelin, and tesamorelin are studied, and it links to the receptor pharmacology that separates that class from a direct hGH fragment like AOD-9604. Researchers designing comparative studies sometimes stock both a fragment and a secretagogue, such as our sermorelin reference material, to keep the two mechanisms distinct within a single project.
Handling notes for the research bench
AOD-9604 ships as a lyophilized powder and should be treated with standard peptide bench practice: keep it frozen and protected from light prior to use, reconstitute immediately before an experiment rather than storing reconstituted solution for extended periods, and use aseptic technique when opening vials. Our guide to reconstituting lyophilized peptides walks through the concentration math for preparing a stock solution at the bench. Because AOD-9604 requires its own extraction protocol to distinguish it from intact hGH or other fragments in a sample, confirming vial identity by mass spectrometry rather than assuming it from the label is good practice; our explainer on how LC-MS confirms peptide identity describes the general method, and the same detection principle underlies the AOD-9604-specific assay reported in the analytical literature (Cox et al., 2015). Our AOD-9604 research material ships with a certificate of analysis for lot-specific verification.
Frequently asked questions
Is AOD-9604 the same molecule as hGH fragment 177-191?
No. hGH fragment 177-191 is the unmodified 15-residue C-terminal sequence of human growth hormone studied in the original Monash mapping work (Wu and Ng, 1993). AOD-9604 is that same sequence with an additional tyrosine joined at the N-terminus, making it a 16-amino-acid analog (Cox et al., 2015). The two are related but distinct research articles.
Is AOD-9604 approved by the FDA?
No. AOD-9604 has never been approved by the FDA as a drug for any indication. FDA has separately reviewed it only in the context of the Section 503A bulk drug substances list for compounding pharmacies, a nomination that was later withdrawn (FDA).
Does AOD-9604 bind the growth hormone receptor the same way hGH does?
Published receptor-binding assays reported that AOD-9604 did not compete for the hGH receptor and did not trigger the receptor-mediated cell proliferation observed with intact hGH in the same cell system (Heffernan et al., 2001).
What models have been used to study AOD-9604?
Published work spans rat adipose tissue and epididymal fat pad assays, obese Zucker rats, obese and lean (ob/ob) mice, hGH-receptor-transfected cell lines, and analytical chemistry work on detecting the peptide in biological samples (Wu and Ng, 1993; Natera et al., 1994; Ng et al., 2000; Heffernan et al., 2001; Cox et al., 2015).
Is AOD-9604 the same thing as a growth hormone secretagogue?
No. AOD-9604 is a direct structural fragment of hGH itself. Secretagogues such as ipamorelin, sermorelin, and CJC-1295 act through ghrelin or GHRH receptors to stimulate the body's own hormone release and do not share AOD-9604's sequence or mechanism. See our growth hormone secretagogues overview for the receptor-level comparison.
What form does Homegrown Peptides supply AOD-9604 in?
As a lyophilized powder intended for laboratory research use only, not for human or animal administration. See the AOD-9604 product page for lot documentation and certificate of analysis.
References
- Wu Z, Ng FM. Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Biochem Mol Biol Int. 1993. PubMed 8358331.
- Natera SH, Jiang WJ, Ng FM. Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. Biochem Mol Biol Int. 1994. PubMed 7987248.
- Ng FM, Sun J, Sharma L, et al.. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000. PubMed 11146367.
- 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. PubMed 11673763.
- Cox HD, Smeal SJ, Hughes CM, et al.. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015. PubMed 25208511.
- Orlovius AK, Thomas A, Schänzer W, et al.. AOD-9604 does not influence the WADA hGH isoform immunoassay. Drug Test Anal. 2013. PubMed 24124033.
- U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks. FDA.gov
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
