Monograph in Growth-hormone axis peptides
AOD-9604
A modified C-terminal fragment of human growth hormone, developed as an obesity drug in the early 2000s. The peer-reviewed record is rodent studies; the human trials were never published in PubMed.
Also called AOD9604 · hGH fragment 177-191 analogue · Tyr-hGH(177-191)
Best evidence: Preclinical only
All peer-reviewed efficacy data we found are from rats and mice. A phase IIa program was reported underway in 2002, but no results are indexed in PubMed.
Not FDA-approved · FDA compounding nomination withdrawn
Residue Editorial Team · updated
What is AOD-9604?
AOD-9604 is a synthetic analog of growth hormone's fat-releasing C-terminal region. In obese rodents it reduced weight gain and raised fat oxidation without full growth hormone's effect on blood sugar, and did not bind the growth-hormone receptor1PubMedIncrease of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Heffernan MA et al. Int J Obes Relat Metab Disord. 2001.,2PubMedMetabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Ng FM et al. Horm Res. 2000.. No human efficacy results are published in PubMed, and FDA lists serious adverse events that may be associated with it3FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..
Key findings
- In obese Zucker rats, oral AOD-9604 at 500 µg/kg for 19 days cut body-weight gain by more than half compared with controls, without impairing insulin sensitivity2.
- In obese mice, both hGH and AOD-9604 reduced weight gain and increased fat oxidation, but AOD-9604 did not cause hyperglycemia, did not compete for the hGH receptor and did not induce cell proliferation1.
- Its fat-reducing effect in mice depended on beta-3 adrenergic receptors: it failed in beta-3 knockout mice4PubMedThe 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. Heffernan M et al. Endocrinology. 2001..
- A 2004 drug-development profile reported phase IIa trials underway by February 20025PubMedAOD-9604 Metabolic. Wilding J Curr Opin Investig Drugs. 2004.; we found no published results.
- AOD-9604 does not interfere with the WADA immunoassay for hGH isoforms6PubMedAOD-9604 does not influence the WADA hGH isoform immunoassay. Orlovius AK et al. Drug Test Anal. 2013..
What is AOD-9604, chemically?
| PubChem CID | 71300630 “Aod-9604” |
|---|---|
| Formula | C78H123N23O23S2 |
| Molecular weight | 1,815.1 g/mol |
| CAS (as listed) | 221231-10-3 |
| FDA UNII | 7UP768IP4M |
| InChIKey | GVIYUKXRXPXMQM-BPXGDYAESA-N |
| Length | 16 residues |
| Route in trials | Oral and intraperitoneal in rodent studies |
| Mechanism | Modified hGH C-terminal fragment; lipolytic, does not bind the GH receptor |
- Hydrophobic
- Polar
- Basic (+)
- Acidic (−)
- Gly / Pro / Cys
How does AOD-9604 work?
Human growth hormone has metabolic actions, including stimulating fat breakdown, that researchers in the 1990s mapped to its C-terminal region. AOD-9604 is a synthetic analog of that "lipolytic domain"2. The key finding of the mouse work is that it does not compete for the hGH receptor and does not stimulate cell proliferation — so whatever it does to fat, it does not do by acting as a small growth hormone1.
The mechanism appears to involve beta-3 adrenergic receptors, the main lipolytic receptor on fat cells. Chronic treatment restored repressed beta-3 receptor RNA in obese mice to lean-mouse levels, and in beta-3 receptor knockout mice neither hGH nor AOD-9604 produced the expected weight loss or lipolysis4.
What have studies found?
Rats. Obese Zucker rats given oral AOD-9604 (500 µg/kg daily for 19 days) gained 15.8 g versus 35.6 g in controls. Their fat tissue showed higher lipolytic activity, and euglycemic clamps showed no adverse effect on insulin sensitivity — in contrast to chronic intact hGH2.
Mice. Both hGH and AOD-9604 reduced body-weight gain in obese mice, with higher fat oxidation and plasma glycerol. Unlike hGH, AOD-9604 did not induce hyperglycemia or reduce insulin secretion1.
Humans. A 2004 drug-development profile stated that phase IIa trials in obesity were underway by February 20025. The full PubMed record for AOD-9604 has only a couple of dozen entries, none tagged as a clinical trial7PubMedPubMed search: (AOD9604[tiab] OR AOD-9604[tiab]). 22 records at fetch., and ClinicalTrials.gov returns no registered studies8TrialClinicalTrials.gov registry search: AOD9604 OR AOD-9604. 0 registered studies at fetch.. The only human-relevant paper in our set is an anti-doping assay study, which found AOD-9604 does not affect the WADA hGH isoform immunoassay6.
Is AOD-9604 FDA-approved?
| Record | Status | Source |
|---|---|---|
| FDA approval | No approved application Drugs@FDA returned no application for “AOD-9604”. | openFDA |
| Compounding: nominated, then withdrawn AOD-9604 | Withdrawn nomination FDA still lists its safety concerns: “Compounded drugs containing AOD-9604 may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. FDA has identified no, or only limited, safety-related information. Therefore, the agency lacks sufficient information to know whether the drug would cause harm when administered to humans. FDA has also…” | 3 |
FDA's entry for AOD-9604 notes possible significant immunogenicity risk and complexities in impurity characterization. It says FDA has identified no, or only limited, safety-related information, so it lacks sufficient information to know whether the drug would cause harm in humans, and it has also identified serious adverse events that may be associated with AOD-9604, though causality is not clear3.
What is still unknown?
- The phase II results. Whatever the early-2000s human trials found has not been published in a PubMed-indexed journal in the records we fetched.
- Translation. Rodent fat-metabolism effects frequently fail to translate to people; without human data, none can be assumed.
What effects has AOD-9604 shown, by body system?
Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.
| System | What was observed | Grade |
|---|---|---|
| Body fat (rodents) | Reduced weight gain and increased lipolysis and fat oxidation in obese rats and mice2,1. | D |
| Glucose (rodents) | No hyperglycemia or loss of insulin sensitivity, unlike intact hGH1,2. | D |
| Human data | No published human efficacy trial indexed in PubMed7. | D |
How much research is there on AOD-9604?
No studies listing AOD-9604 as an intervention were returned by ClinicalTrials.gov at the last fetch.
Compare and continue
- AOD-9604 vs tesamorelinComparison
- TesamorelinGrowth-hormone axis peptides
- IpamorelinGrowth-hormone axis peptides
- CJC-1295Growth-hormone axis peptides
Questions readers ask
Is AOD-9604 FDA-approved?
No. Drugs@FDA has no application for it. FDA lists AOD-9604 among withdrawn compounding nominations, says it lacks sufficient information to know whether the drug would cause harm in humans, and notes serious adverse events that may be associated with it, though causality is not clear3.
How is AOD-9604 different from growth hormone?
It is a modified fragment from the C-terminus of hGH. In mice, it reduced weight gain like hGH but did not bind the hGH receptor, raise blood sugar or stimulate cell proliferation1.
References
Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.
- 1 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. PMID 11673763; doi:10.1038/sj.ijo.0801740.
- 2 PubMed Ng FM, Sun J, Sharma L, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res 2000. PMID 11146367; doi:10.1159/000053183.
- 3 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
- 4 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. PMID 11713213; doi:10.1210/endo.142.12.8522.
- 5 PubMed Wilding J. AOD-9604 Metabolic. Curr Opin Investig Drugs 2004. PMID 15134286.
- 6 PubMed Orlovius AK, Thomas A, Schänzer W, et al. AOD-9604 does not influence the WADA hGH isoform immunoassay. Drug Test Anal 2013. PMID 24124033; doi:10.1002/dta.1557.
- 7 PubMed PubMed search: (AOD9604[tiab] OR AOD-9604[tiab]). 22 records at fetch. PMID aod-9604.
- 8 ClinicalTrials.gov ClinicalTrials.gov registry search: AOD9604 OR AOD-9604. 0 registered studies at fetch.
- 9 FDA EGRIFTA SV prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-07-29.