AOD-9604 5 mg

AOD-9604 is a synthetic hexadecapeptide. Its sequence is Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe, closed by a single disulfide bridge between the cysteine residues at positions 7 and 14. The molecular formula is C78H123N23O23S2 and the average molecular mass is 1815.1 g/mol. It carries no lipidation, no PEG chain and no other modification; the disulfide is the only ring closure in the molecule.

The sequence is taken from the C-terminal region of human growth hormone, a 191-residue protein. The primary literature describes AOD-9604 as hGH(177-191) with an additional tyrosine at the N-terminus, added for stabilisation (Stier et al., 2013; Cox et al., 2015). Catalogue listings often render the same molecule as "hGH fragment 176-191". The two labels point to the same compound but not to the same native sequence: residue 176 of mature human growth hormone is phenylalanine, so the tyrosine at position 1 of AOD-9604 is a substitution, not a copy of the parent protein. Anyone comparing a certificate of analysis against a reference sequence should work from the sixteen residues listed above rather than from the hGH numbering.

The peptide was developed under the code AOD9604 by Metabolic Pharmaceuticals Limited (Valentino et al., 2010), working from research carried out at Monash University in Melbourne, the affiliation listed on the founding rodent papers. Development as an obesity drug candidate was terminated in 2007 (Valentino et al., 2010). The molecule did not stop there. The FDA substance registry holds it as a single record, UNII 7UP768IP4M, CAS 221231-10-3, under the preferred name LAT-8881, with AOD-9604 and AOD9604 as synonyms; work published under the LAT-8881 code continues to appear (Harpur et al., 2023; Spanswick et al., 2026). Supplied lyophilised. For laboratory research use only, not for human consumption.

The published record on AOD-9604 opens with rodent obesity models. Ng and colleagues treated obese Zucker rats with an oral dose of 500 micrograms per kilogram of body weight per day for 19 days. They reported body weight gain of 15.8 plus or minus 0.6 g in the treated animals against 35.6 plus or minus 0.8 g in controls, a difference the authors characterised as a reduction of more than 50 percent, together with increased lipolytic activity in adipose tissue. Euglycaemic clamp measurements in the same animals showed no adverse effect on insulin sensitivity, which the authors contrasted with chronic treatment using intact hGH (Ng et al., 2000). Heffernan and colleagues subsequently treated obese (ob/ob) and lean C57BL/6J mice for 14 days using mini-osmotic pumps, measuring body weight, caloric intake, resting energy expenditure, fat and glucose oxidation, and plasma glucose, insulin and glycerol. They reported reduced body weight gain in the obese animals alongside increased in vivo fat oxidation and increased plasma glycerol, and, unlike hGH, no induced hyperglycaemia (Heffernan et al., 2001a).

The same 2001 paper tested receptor interaction directly. In BaF-BO3 cells transfected with the human GH receptor, AOD9604 did not compete for 125I-hGH binding and did not induce cell proliferation, whereas hGH did both (Heffernan et al., 2001a). A companion study looked at the beta-3 adrenergic receptor. After 14 days of intraperitoneal administration in obese mice the authors reported increased beta-3 AR RNA expression, restored to levels comparable with lean animals, and in beta-3 AR knockout mice long-term treatment with either hGH or AOD9604 failed to produce the body weight and lipolysis changes seen in wild-type controls. The authors' own conclusion is more guarded than the knockout result on its own implies. Because AOD9604 still increased energy expenditure and fat oxidation in the knockout animals in an acute experiment, they concluded that the lipolytic actions of both compounds are not mediated directly through the beta-3 AR, although both increase its expression (Heffernan et al., 2001b). Secondary write-ups frequently invert this and describe the receptor as an obligate part of the mechanism; the paper does not say that.

The human obesity programme is unusually well documented for a compound of this class, because the sponsor's trials were later summarised in a single paper. Stier and colleagues described six randomised, double-blind, placebo-controlled studies run between 2001 and 2006 with 893 participants in total. The programme ran from a phase I intravenous dose escalation (25 to 400 micrograms per kilogram, 15 healthy adult male volunteers) through three phase IIa studies (an intravenous single-dose study, an oral single-dose study and a seven-day oral multiple-dose study) to two long-term oral trials: a 12-week study in 300 clinically obese participants and a 24-week study in 502 obese adults. Across the programme the authors reported no effect on serum IGF-1, no significant changes or trends in oral glucose tolerance testing, and no anti-AOD9604 antibodies detected in the samples assayed. They also recorded five serious adverse events in the 12-week trial, three in the 20 mg arm (basal cell carcinoma, lipoma, squamous cell carcinoma), one in the 5 mg arm (breast cancer) and one in the 10 mg arm (malignant melanoma), and concluded that no withdrawal or serious adverse event in any of the six studies was related to intake of AOD9604 (Stier et al., 2013). The paper is written by and for the sponsor, in support of a food-ingredient safety position, and should be read with that in mind.

Efficacy is where that programme stopped. A 2010 review of anti-obesity pharmacotherapy reported that in a 12-week randomised trial participants receiving 1 mg per day lost an average of 2.6 kg against 0.8 kg in the placebo group, and that the response was not dose-dependent, with the 10 mg per day group showing a smaller reduction. The same review states that development was terminated in 2007 after a 24-week trial in 536 subjects failed to induce significant weight loss, and notes a 2009 agreement licensing the peptide for evaluation as a transdermal cosmeceutical ingredient (Valentino et al., 2010). The subject count for the 24-week trial differs between sources: Stier and colleagues give 502.

Outside metabolism the literature divides into two strands. The larger is analytical and anti-doping. Cox and colleagues validated a solid-phase extraction method for AOD9604 in urine with a limit of detection of 50 pg/mL, identified six candidate metabolites after incubation of the peptide in serum and urine, and found one metabolite corresponding to residues CRSVEGSCG that was substantially more stable than the parent compound; their paper states the peptide is banned by the World Anti-Doping Agency (Cox et al., 2015). Orlovius and colleagues published a short report titled "AOD-9604 does not influence the WADA hGH isoform immunoassay" (Orlovius et al., 2013). Vanhee and colleagues reported the identification and characterisation of the peptide in unlabelled pharmaceutical preparations seized by the Belgian authorities (Vanhee et al., 2014).

The second strand follows the molecule after the obesity programme ended, and it is the part most merchant copy omits. Kwon and Park used a collagenase-induced knee osteoarthritis model in 32 New Zealand white rabbits randomised to four weekly intra-articular injection groups: saline, 6 mg hyaluronic acid, 0.25 mg AOD9604, and 0.25 mg AOD9604 combined with 6 mg hyaluronic acid, with gross morphology, histopathology and lameness duration scored at eight weeks (Kwon and Park, 2015). Under the later code LAT-8881, Spanswick and colleagues reported that the peptide reversed mechanical allodynia in several rodent neuropathic models and identified lanthionine synthetase C-like protein 1 as its binding target in spinal cord, validated by siRNA knockdown; several authors declare employment, shareholding or advisory roles with the sponsor, Lateral Pharma (Spanswick et al., 2026). Harpur and colleagues tested it in a mouse model of severe influenza A infection and state in that paper that LAT8881 has been assessed in clinical trials for the treatment of obesity and of neuropathy (Harpur et al., 2023). A systematic review of investigational postherpetic neuralgia drugs lists LAT8881, as a LANCL activator, among fifteen molecules covered by phase II to IV trials registered or published between 2016 and 2023 (Huerta et al., 2023). Two things follow. The human record is not confined to the terminated obesity programme, and while the founding mechanistic work of 2000 and 2001 does come from a single group at Monash University, the later work does not.