SS-31 (elamipretide): what the research shows

What SS-31 is

SS-31 is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2,6-dimethyltyrosine, a non-standard amino acid, and the C-terminus is amidated. It belongs to the Szeto-Schiller family of peptides, a series designed in the early 2000s by Hazel Szeto and Peter Schiller and numbered in sequence; SS-31 is the member that went furthest. The D-arginine at the N-terminus and the unnatural tyrosine make it unusually resistant to the peptidases that clear ordinary short peptides.

The molecule's defining property is where it goes. Its alternating aromatic-cationic motif lets it cross the plasma membrane without a transporter and then concentrate in the inner mitochondrial membrane, where it binds cardiolipin, a phospholipid found almost exclusively in that membrane. Most of the literature follows from that single interaction.

The same compound appears under several names. Elamipretide is the international non-proprietary name used in clinical development; MTP-131 and Bendavia are earlier development codes and trade names. On a research catalogue, SS-31 is the name that persists, and it is the name on our product page and certificate.

The mechanism the literature studied

Cardiolipin does structural work. It holds the folds of the inner membrane, the cristae, in their tight curvature, and it anchors the complexes of the electron transport chain into supercomplexes so that electrons pass between them efficiently. When cardiolipin is oxidised or lost, cristae loosen, the complexes drift apart, and more electrons leak out of the chain to form reactive oxygen species, which oxidise more cardiolipin. That feedback loop is the injury model much of the field works from.

SS-31 is proposed to interrupt it by binding cardiolipin directly. The published work associates that binding with preserved cristae architecture, better-organised supercomplexes, higher ATP output per unit of oxygen consumed, and lower electron leak. Several studies also report that it blocks cardiolipin from converting cytochrome c into a peroxidase, which is one of the early steps in the intrinsic apoptosis pathway.

What it is not is a free-radical scavenger in the conventional sense. Its measured antioxidant capacity in solution is modest; the reduction in reactive oxygen species reported in cells is attributed to the chain leaking less, not to the peptide mopping up what leaks. That distinction is why it is used as a mechanistic probe rather than as another antioxidant.

The preclinical models

Ischemia-reperfusion is the largest group. Isolated perfused hearts from rats and guinea pigs, coronary-occlusion models in rabbits and sheep, and renal artery clamp models in rats are the usual formats, with infarct size, tissue ATP, mitochondrial respiration and markers of oxidative damage as endpoints. Kidney work extends into angiotensin II hypertension models, renal artery stenosis in pigs, and rodent models of diabetic and contrast-induced kidney injury.

Heart failure models include pressure overload by aortic constriction in mice, pacing-induced failure in dogs, and angiotensin II infusion, where the readouts are ventricular function, fibrosis and mitochondrial proteomics. In skeletal muscle, the work is mostly in aged mice: mitochondrial energetics measured in vivo by phosphorus magnetic resonance and ex vivo in permeabilised fibres, with fatigue resistance and cristae ultrastructure alongside.

Retinal studies use mouse models of light-induced and age-related retinal degeneration, diabetic retinopathy and inherited optic neuropathy, together with retinal pigment epithelium cell culture under oxidative stress. Isolated-mitochondria and liposome experiments underpin all of it, and they are where the cardiolipin-binding claim was actually measured. Every one of these is an animal, tissue or cell study; none establishes what the molecule does in a person.

Clinical development as elamipretide

SS-31 is unusual among research peptides in having a full clinical development history. It went into trials as elamipretide across a series of conditions in which mitochondrial dysfunction is the proposed cause, and the results are mixed enough to be worth stating plainly.

In primary mitochondrial myopathy, a late-stage trial did not meet its primary endpoints of walking distance and fatigue. In dry age-related macular degeneration, a mid-stage trial missed its primary endpoints while reporting signals on retinal structure that led to a further late-stage programme. In Barth syndrome, a rare inherited cardiolipin disorder, a small crossover trial did not meet its endpoints in the randomised phase; longer open-label follow-up was the basis for a regulatory submission that first drew a complete response letter and then, in 2025, an accelerated approval in the United States restricted to that indication and conditional on a confirmatory study. Earlier trials in heart failure and reperfusion after heart attack were negative or inconclusive.

None of this changes what the vial on our shelf is. A research-use-only reference standard is not the drug product, and no elamipretide product is authorised in Canada. The clinical record is useful context for reading the preclinical literature, not evidence about what research material does.

Why it is grouped with NAD+ and MOTS-c

The three compounds on our longevity shelf at /research/longevity/ share a subject rather than a mechanism. Each is studied for its effect on mitochondrial function, and each reaches it by a different route. NAD+ is a coenzyme, the redox carrier that moves electrons into the transport chain and the substrate that sirtuins and PARP enzymes consume; its library entry is at /library/nad/. MOTS-c is a peptide encoded in the mitochondrial genome that acts as a signal, moving to the nucleus under stress and altering metabolic gene expression; see /library/mots-c/.

SS-31 is the structural one. It does not supply a substrate or send a signal; it binds a membrane lipid and changes how the machinery embedded in that membrane is organised. An investigator building a panel of mitochondrial tool compounds has one from each category: substrate, signal, structure. That is the logic of the grouping, and it is the whole of it. Being sold on the same page implies nothing about combined use, and there is no controlled human evidence on any pairing. The SS-31 dictionary entry is at /library/ss-31/.

Stability, storage and reconstitution

SS-31 ships as a lyophilised powder in a sealed vial, in 10 mg and 50 mg sizes. As a short peptide with a D-amino acid and a non-standard tyrosine, it is more stable in the dry state than most catalogue peptides, but the same handling rules apply. Keep unopened vials refrigerated, or frozen for storage beyond a few months, dry and out of light. Lyophilised material is hygroscopic; let a cold vial reach room temperature before opening it so that condensation does not land on the powder.

Reconstitution uses bacteriostatic water, run slowly down the inside wall of the vial rather than onto the powder, followed by gentle swirling until the solution is clear. Do not shake. Once in solution, keep at 2 to 8 C, avoid repeated freezing and thawing, and discard anything that turns cloudy or shows particulates. Our general reconstitution guide is at /library/bacteriostatic-water-reconstitution/.

Diluent volume, the resulting concentration and everything downstream of that is protocol, and it is deliberately not on this page. The reported protocol for SS-31, including a concentration table computed from the vial masses we actually ship, is at /protocols/ss-31/.

Reading the certificate for an SS-31 lot

Pure North commissioned Canada Peptide Testing, as a paying client. Published reports for this product: 10 mg vial, CPT-SS31-10-091226 (99.46% area purity; 10.28 mg measured content). Read the original documents at /lab-results/.

The published Canada Peptide Testing reports measure RP-HPLC-UV area purity and content. They do not include mass-spectrometry identity, endotoxin, water content or a related-substances breakdown. These results do not establish clinical safety or regulatory approval.

Match the compound, vial size and printed lot to the report before relying on it. An assigned reference is not automatically the batch code on a vial. If they differ, email purenorthpeptides@proton.me with the vial details and report number to confirm the connection. Do not extend a report to another size or lot.

Regulatory status in Canada

SS-31 is supplied in Canada as a research-use-only laboratory reference standard. It is not approved by Health Canada for any use in people and carries no Drug Identification Number or Natural Product Number. The accelerated approval elamipretide holds in the United States is for one rare condition, applies to that manufacturer's drug product, and does not extend to research material or to Canada. That is the category the vial sits in, and it constrains what we can say: no health claims and no outcomes. The schedules that appear on the protocol page summarise what the literature reports; they are not a recommendation, and they carry the same research-use framing as this page.

Every order requires a research-use declaration at checkout confirming that the material is for laboratory research. That is the buyer's side of the same category.

This page is general information, not legal advice. Classification is compound-specific and can change, Health Canada is the authority, and our overview of the research-use framework is at /library/are-research-peptides-legal-in-canada/.

Frequently asked

What is SS-31?

SS-31 is a synthetic tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2, from the Szeto-Schiller series. It crosses cell membranes without a transporter, concentrates in the inner mitochondrial membrane and binds cardiolipin, which is why it is used as a tool compound in bioenergetics research. It is supplied as a research-use-only laboratory reference standard.

Is SS-31 the same as elamipretide?

Yes, chemically. Elamipretide is the non-proprietary name given to SS-31 for clinical development, and MTP-131 and Bendavia are earlier codes for the same molecule. The research-use-only reference standard we sell is not the approved drug product, which is manufactured, formulated and regulated separately.

What has SS-31 been studied for?

In preclinical research the question is what the molecule does in a given model. SS-31 has been studied in isolated-mitochondria and cardiolipin-liposome binding experiments, ischemia-reperfusion models of the heart and kidney in rodents, rabbits, pigs and sheep, heart-failure models in mice and dogs, aged-mouse skeletal muscle energetics, and mouse retinal degeneration models with retinal pigment epithelium cell culture. Those studies report effects on cristae structure, electron transport efficiency, ATP output and reactive oxygen species in those systems. None of it is human evidence about research material.

How is SS-31 stored?

Lyophilised vials are kept refrigerated, or frozen for longer storage, dry and out of light. After reconstitution with bacteriostatic water the solution is kept at 2 to 8 C, not repeatedly frozen and thawed, and discarded if it turns cloudy. Let a cold vial reach room temperature before opening it so condensation stays off the powder.

Is SS-31 legal in Canada?

It is sold as a research-use-only laboratory reference standard, a category distinct from products approved for human use. It is not approved by Health Canada and carries no DIN or NPN, and buyers sign a research-use declaration at checkout. The United States accelerated approval of elamipretide for Barth syndrome does not apply to research material or in Canada. Classification can change; confirm your own position with Health Canada rather than with a supplier's website.

Referenced in our catalog