AOD 9604
[CAS# 221231-10-3]

Identification

• Classification: Biological >> Proteins and peptides >> Hormone
• Name: AOD 9604
• Synonyms: (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
• Protein Sequence: YLRIVQCRSVEGSCGF
• Molecular Formula: C₇₈H₁₂₃N₂₃O₂₃S₂
• Molecular Weight: 1815.08
• CAS Registry Number: 221231-10-3 (386264-39-7)
• 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

• Density: 1.5±0.1 g/cm³ Calc.^*
• Index of refraction: 1.667 (Calc.)^*

Discovory and Applicatios

AOD 9604 is a synthetic peptide fragment derived from the C‑terminal sequence of human growth hormone. The peptide corresponds to amino acids 176–191 of the full growth hormone molecule, with a tyrosine residue added to enhance stability. It was originally developed in the late 1990s by researchers seeking to isolate the part of growth hormone responsible for fat‑metabolism effects, specifically stimulation of fat breakdown (lipolysis) and inhibition of fat formation (lipogenesis), without triggering the systemic endocrine effects associated with full‑length hormone administration. Preclinical research in obese animal models showed that AOD 9604 can reduce weight gain, increase fat oxidation and enhance lipolytic sensitivity, effects that were associated with increased expression of lipolytic receptors in adipose tissue.

AOD 9604 does not bind to or activate the conventional growth hormone receptor and does not stimulate the secretion of insulin‑like growth factor‑1, distinguishing its activity from that of intact growth hormone. In rodent studies, chronic administration of AOD 9604 resulted in body fat reduction and increased markers of fat oxidation without causing hyperglycemia or increased insulin secretion, which are common side effects of growth hormone therapy. These findings underscored the potential of AOD 9604 as a targeted modulator of adipose tissue metabolism rather than a general anabolic agent.

Human clinical research on AOD 9604 has been limited. Multiple early clinical trials were conducted to assess safety and tolerability, and these studies generally reported a favorable safety profile indistinguishable from placebo, with no evidence of adverse effects typically seen with systemic growth hormone therapy. However, efficacy results in controlled human weight‑loss trials were inconsistent or statistically modest. A larger Phase IIb trial did not demonstrate a significant weight‑loss benefit compared with placebo, and development of AOD 9604 as a therapeutic agent for obesity was discontinued by its developers in the mid‑2000s. As a result, AOD 9604 has not received regulatory approval for the treatment of obesity or any other medical indication in major jurisdictions.

Mechanistically, AOD 9604’s effects on fat metabolism are still under investigation. Preclinical models indicate interactions with adipose‑tissue signaling pathways that enhance lipolysis and fat oxidation. Although early hypotheses suggested involvement of β‑adrenergic receptors, subsequent studies in receptor knockout models showed that the peptide’s actions are not entirely dependent on a single receptor pathway, implying broader regulatory effects on adipose tissue metabolism. Research also continues into potential applications in areas such as cartilage repair and metabolic regulation, although these applications remain experimental and lack convincing clinical evidence.

AOD 9604 has attracted interest beyond academic research because of its purported metabolic effects, and it is often discussed in non‑clinical contexts such as athletic performance and weight management communities. It has also been classified as a prohibited substance for athletic competition by anti‑doping authorities, reflecting concerns that peptides with metabolic activity might confer unfair advantages. Because AOD 9604 remains an investigational compound without regulatory approval, its use outside controlled research settings is not sanctioned, and healthcare providers generally do not prescribe it for medical indications.

Overall, AOD 9604 represents a targeted peptide fragment derived from human growth hormone that demonstrated promising fat‑metabolism effects in animal studies and was well‑tolerated in early human trials. However, the lack of consistent evidence of therapeutic efficacy in weight‑loss clinical trials has limited its development as an approved treatment. Its primary value today lies in research settings as a tool to explore mechanisms of adipose tissue regulation and metabolic signaling pathways distinct from classical growth hormone activity.

References

Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM (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

Heffernan M, Ng FM, et al. Safety and tolerability of the hexadecapeptide AOD9604 in humans. Journal of Endocrinology and Metabolism (2013) article detailing clinical study safety profiles.

Principal clinical trials report on AOD9604 development termination due to lack of statistically significant weight‑loss efficacy in Phase IIb trials (development terminated 2007).