AOD-9604 vs SS-31
AOD-9604 and SS-31 are studied in overlapping research areas, which is why they are frequently compared. This is a neutral side-by-side reference drawn from published preclinical literature and laboratory handling data.
How they actually differ
Comparing the two: AOD-9604 is 16-residue hgh c-terminal fragment analogue with one intramolecular disulfide, while SS-31 is mitochondria-targeting aromatic-cationic tetrapeptide (cardiolipin-binding) — different molecular classes with different handling consequences; their leading degradation routes differ (disulfide exchange (scrambling) and formation of disulfide-linked dimers, accelerated above about ph 8. for AOD-9604, adsorptive loss to plasticware from the cationic charge for SS-31), so the storage precautions that matter are not the same; their practical working windows differ once reconstituted. The sections below set out each in full.
AOD-9604 — origin
AOD-9604 is residues 177-191 of human growth hormone with an extra tyrosine added at the N-terminus (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe), closed by a disulfide between the two cysteines. It came out of Frank Ng's group at Monash University in Australia and was developed by Metabolic Pharmaceuticals in Melbourne as an obesity candidate. That programme was discontinued in 2007 after a 24-week phase 2b trial did not show a clinically meaningful outcome, and the compound never reached approval as a medicine.
SS-31 — origin
SS-31 (Elamipretide) is a Szeto-Schiller aromatic-cationic tetrapeptide (D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2) that concentrates in the inner mitochondrial membrane and binds cardiolipin, the lipid unique to that membrane. Its structure is the reason it is studied specifically at the mitochondrion rather than as a general antioxidant.
AOD-9604 research themes
Heffernan et al. (Endocrinology 2001) compared hGH and AOD9604 over 14 days in obese mice and in β3-adrenergic-receptor knockout mice. Both raised the repressed β3-AR expression in obese mice, but neither changed body weight or lipolysis in the knockout mice over the long-term protocol, leading the authors to conclude the lipolytic actions were not mediated directly through β3-AR.
Ng et al. (Horm Res 2000) studied oral administration of AOD9604 in obese Zucker rats, reporting reduced body-weight gain and increased adipose lipolytic activity, and — unlike intact hGH — no impairment of insulin sensitivity on euglycaemic clamp.
Stier et al. (J Endocrinol Metab 2013) pooled six randomised, double-blind, placebo-controlled trials and reported no change in serum IGF-1, no adverse effect on carbohydrate metabolism, and no anti-AOD9604 antibodies in tested participants. The same development programme did not show a clinically meaningful weight outcome.
Kwon and Park (Ann Clin Lab Sci 2015) gave intra-articular AOD9604, with or without hyaluronic acid, in a collagenase-induced knee osteoarthritis model in rabbits and scored cartilage morphology, histology and lameness.
SS-31 research themes
Studied for selective association with cardiolipin in the inner mitochondrial membrane, the basis of its mitochondrial targeting.
Examined for effects on mitochondrial energy production in research models of mitochondrial dysfunction.
Investigated around reactive-oxygen-species handling at the mitochondrion.
AOD-9604 handling
- Let the vial reach room temperature before opening.
- Add diluent gently down the vial wall and swirl; do not vortex.
- Keep reducing agents (DTT, TCEP, β-mercaptoethanol) and alkaline buffers away from the stock.
- Label aliquots with reconstitution date and diluent.
SS-31 handling
- Reach room temperature before opening.
- Use low-bind labware and buffers at low working concentrations to limit adsorption of the cationic peptide.
- Aliquot and refrigerate.
Both third-party tested
Every Popular Peptides batch of AOD-9604 and SS-31 is independently tested by HPLC and LC-MS with a published Certificate of Analysis. Enter a lot number to pull the COA for a specific vial.
AOD-9604 reference
Related comparisons
AOD-9604 and SS-31 are supplied strictly as research chemicals for in-vitro laboratory and research use only. They are not intended for human or animal consumption, diagnostic, or therapeutic use. This comparison summarizes published preclinical literature and laboratory handling data; it is not medical advice, not a claim of efficacy, and not usage guidance.