SS-31 10mg

SS-31 is a synthetic peptide built from only four amino acids. Two of those residues are non-standard, and that is the point. Position one carries D-arginine rather than the ordinary L-form, and position two carries 2',6'-dimethyltyrosine, an aromatic residue not found in natural proteins. The chain ends in an amide group. This short aromatic-cationic design belongs to the Szeto-Schiller peptide family, named for the two researchers who first developed the class for mitochondrial work.

The compound is best known by its International Nonproprietary Name, elamipretide, and by the development code MTP-131. The label SS-31 comes from the original Szeto-Schiller numbering. All three names describe the same tetrapeptide. Researchers reading older and newer literature will encounter every variant, and the page uses them interchangeably.

What sets this compound apart from most research peptides is where it goes once inside a cell. The alternating positive charge and aromatic bulk let the compound cross membranes and gather in the inner mitochondrial membrane, and it does so without depending on the membrane voltage that most mitochondrial probes require, a property documented during the development of the peptide class (PMID 19076436). Once concentrated there, the compound associates with cardiolipin, the four-tailed phospholipid that defines the inner membrane and shapes the folds called cristae.

SS-31 is supplied as a lyophilized — freeze-dried — white-to-off-white powder in a sealed amber-glass vial under inert gas. Each vial contains 10 mg of peptide. Reconstitution with bacteriostatic water is required before the peptide can be drawn into an insulin syringe. Reconstitution mechanics are covered in the Reconstitution accordion.

The research record on SS-31 is broad and, unusually for a research peptide, includes several published human clinical trials alongside the preclinical work. Mechanism research has converged on the cardiolipin interaction (PMID 32273339), while disease-model work spans cardiac, renal, neurological, and skeletal-muscle systems. The clinical trials — in heart failure and in primary mitochondrial myopathy — have produced mixed and often null primary results, a fact this listing reports plainly rather than glossing.

No regulatory authority — Health Canada, the FDA, the EMA, the TGA, or any equivalent — has cleared SS-31 for therapeutic use in humans or animals. Ronin Peptides ships the compound exclusively as a research-grade reagent for benchwork. Dosing protocols, treatment regimens, and administration instructions are out of scope and are not provided in any form.

The mechanistic centre of SS-31 research is its binding to cardiolipin. A 2020 study in the Journal of Biological Chemistry demonstrated that the peptide associates with lipid bilayers and changes their surface electrostatics, and the authors argued that this physical interaction — not a simple chemical scavenging action — is the key component of how the molecule works (PMID 32273339). Cardiolipin is concentrated in the inner mitochondrial membrane, so a peptide that targets cardiolipin is, in effect, targeting the machinery of energy production directly.

The mitochondrial targeting itself is a property of the sequence. The aromatic-cationic Szeto-Schiller design lets the compound partition into the inner membrane and accumulate there independent of membrane potential, a behaviour documented and measured across the early development of the peptide class (PMID 19076436). This distinguishes it from charge-driven mitochondrial probes, which require an intact membrane voltage and therefore fail in exactly the damaged mitochondria that are most of interest.

Downstream of the cardiolipin interaction, reviews have compiled a consistent set of preclinical observations: stabilisation of cristae architecture, protection of electron-transport-chain supercomplex organisation, improved efficiency of ATP synthesis, and reduced generation of mitochondrial reactive oxygen species (PMID 35037146, PMID 34302976). The framing has shifted over time. Earlier papers described SS-31 as a mitochondria-targeted antioxidant; current reviews treat the reduced oxidative output as a consequence of the structural cardiolipin interaction rather than as the primary action.

An early in-vivo demonstration anchored the field. A 2011 study reported that the peptide accelerated ATP recovery and reduced injury in a renal ischemia-reperfusion model, linking the membrane-level mechanism to a measurable functional outcome in living tissue (PMID 21546574). Mechanism research remains active, and recent reviews continue to refine the cardiolipin model and map it onto the various disease systems in which the compound has been studied (PMID 39940712, PMID 40294492).

Cardiac research is one of the largest streams. The compound has been examined extensively in heart-failure models, and unusually for a research peptide, it has also been investigated in a published human trial. A 2017 randomized, placebo-controlled phase 2 study delivered a single intravenous infusion to patients with heart failure and reduced ejection fraction (PMID 29217757). The trial is important precisely because its primary findings were modest: it marks the gap between encouraging preclinical cardiac data and the harder reality of controlled human results.

Primary mitochondrial myopathy is the most-developed clinical program. A 2018 randomized dose-escalation study established a starting point in adults with the condition (PMID 29500292), followed by a 2020 crossover trial (PMID 32096613). The pivotal phase 3 trial, MMPOWER-3, was published in 2023 and did not meet its co-primary endpoints (PMID 37268435). Researchers reviewing SS-31 should weigh this outcome carefully: the compound has a fuller clinical record than most research peptides, and that record includes a large negative trial.

Neurological and neuroinflammatory models form a third stream. A 2019 study reported that the compound improved markers of mitochondrial dysfunction along with synaptic and memory measures in a lipopolysaccharide-challenge mouse model, where investigators measured both cognitive and biochemical endpoints (PMID 31747905). A 2021 review surveyed the peptide across diabetic and Alzheimer's-disease preclinical contexts, organising the metabolic and neurodegenerative findings under the shared theme of mitochondrial dysfunction (PMID 34302976).

The renal and ischemia-reperfusion work runs back to the foundational period of the field, where the ATP-recovery and injury-reduction findings first connected the membrane-level mechanism to organ-level outcomes (PMID 21546574). Across these systems the common thread is mitochondrial energetics rather than any single tissue, which is why reviews tend to organise the SS-31 literature by mechanism rather than by organ (PMID 35037146).

Translation to approved clinical use has not occurred. Despite the breadth of preclinical work and the existence of several human trials, the two pivotal controlled studies — in heart failure and in primary mitochondrial myopathy — largely missed their primary endpoints (PMID 29217757, PMID 37268435). Researchers planning new work should review the most current literature before designing protocols, with attention to that preclinical-to-clinical gap and to the evolving cardiolipin mechanism (PMID 40294492).

Unopened lyophilized vials hold up well under dry ambient storage; usable activity persists for several weeks even without refrigeration. The recommended container is the unopened original vial — keep the seal intact until reconstitution. Refrigeration at 2–8 °C is appropriate once the working timeline extends past a month. A standard freezer at −20 °C handles archival storage; ultra-low storage at −80 °C is rarely needed for typical bench-research timescales.

Keep vials shielded from light, ideally in their original outer packaging. Repeated temperature cycling accelerates degradation noticeably more than steady storage at any single temperature inside the recommended bands — minimise transitions between cold and ambient.

After reconstitution, refrigerate the solution at 2–8 °C without delay. The typical working window for a reconstituted preparation is four to six weeks at fridge temperature. Past that window, peptide concentration drifts downward through chemical degradation pathways even though the bacteriostatic water's benzyl alcohol still suppresses microbial growth. The 0.9% benzyl alcohol holds back bacterial contamination — the dominant spoilage path — but does not arrest the slower hydrolysis, oxidation, and aggregation processes that accumulate in any aqueous peptide solution.

When a research timeline extends past six weeks, common practice is splitting the reconstituted solution into single-use volumes and freezing them at −20 °C immediately. Ice-crystal formation during each freeze-thaw cycle inflicts mechanical damage on peptide chains, and pre-splitting eliminates the cumulative loss that comes from thawing one vial multiple times. Thaw individual aliquots overnight in a refrigerator — never at room temperature — and use them within a few days of thaw.

The reconstituted product should be visually clear and colourless. Discard any vial showing turbidity, suspended particulate, yellowing, or visible precipitate. The diluent of choice is USP-grade bacteriostatic water containing 0.9% benzyl alcohol — see the bacteriostatic water product page for reconstitution-grade water.

SS-31 sits in the mitochondrial and longevity-adjacent group rather than the tissue-repair group. It acts at the inner mitochondrial membrane directly, while MOTS-c works through mitochondrial-derived signalling and AMPK, and NAD+ supplies a redox cofactor for energy metabolism. Researchers exploring mitochondrial energetics often examine these compounds as related but mechanistically distinct lines of investigation.

A 10 mg vial of SS-31 reconstituted with 2 mL of bacteriostatic water yields a final concentration of 5 mg/mL, or 5,000 mcg/mL. Other diluent volumes scale linearly: 1 mL gives 10 mg/mL, 3 mL gives approximately 3.33 mg/mL, 5 mL gives 2 mg/mL.

Reconstitution procedure:

1. Bring both vials — peptide and bacteriostatic water — to room temperature before opening.
2. Sanitise both rubber stoppers with an alcohol swab.
3. Pull the chosen diluent volume into a sterile transfer syringe.
4. Direct the water against the inner wall of the peptide vial as it is injected — never onto the lyophilized cake, since direct impact foams the solution and denatures peptide at the air-water interface.
5. Invert slowly or swirl gently until everything dissolves. Do not vortex; do not shake.
6. Refrigerate at 2–8 °C the moment reconstitution completes.

A finished preparation should be visually transparent with no suspended particulate. If the solution is hazy or contains visible material, treat it as degraded or contaminated and discard.

For dose-volume calculations on insulin syringes, use the Ronin peptide reconstitution calculator. The calculator pre-loads vial size and converts target volumes to U-100 syringe units automatically.

In published research, SS-31 has been administered by intravenous infusion in the heart-failure trial and by subcutaneous injection in the mitochondrial-myopathy program, with preclinical studies also using intraperitoneal routes in rodents (PMID 29217757, PMID 37268435, PMID 21546574). These figures are research-reference only — Ronin Peptides does not provide dosing recommendations or administration instructions for any non-laboratory purpose.

1. Mitchell W et al. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. J Biol Chem. 2020;295(21):7452-7469. PMID: 32273339 | doi:10.1074/jbc.RA119.012094
2. Szeto HH et al. Development of mitochondria-targeted aromatic-cationic peptides for neurodegenerative diseases. Ann N Y Acad Sci. 2008;1147:112-121. PMID: 19076436 | doi:10.1196/annals.1427.013
3. Szeto HH et al. Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury. J Am Soc Nephrol. 2011;22(6):1041-1052. PMID: 21546574 | doi:10.1681/ASN.2010080808
4. Daubert MA et al. Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. Circ Heart Fail. 2017;10(12):e004389. PMID: 29217757 | doi:10.1161/CIRCHEARTFAILURE.117.004389
5. Karaa A et al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. 2018;90(14):e1212-e1221. PMID: 29500292 | doi:10.1212/WNL.0000000000005255
6. Karaa A et al. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. J Cachexia Sarcopenia Muscle. 2020;11(4):909-918. PMID: 32096613 | doi:10.1002/jcsm.12559
7. Karaa A et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023;101(3):e238-e252. PMID: 37268435 | doi:10.1212/WNL.0000000000207402
8. Obi C et al. Targeting mitochondrial dysfunction with elamipretide. Heart Fail Rev. 2022;27(5):1925-1932. PMID: 35037146 | doi:10.1007/s10741-021-10199-2
9. Ding XW et al. Mitochondrial dysfunction and beneficial effects of mitochondria-targeted small peptide SS-31 in Diabetes Mellitus and Alzheimer's disease. Pharmacol Res. 2021;171:105783. PMID: 34302976 | doi:10.1016/j.phrs.2021.105783
10. Zhao W et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice. J Neuroinflammation. 2019;16(1):230. PMID: 31747905 | doi:10.1186/s12974-019-1627-9