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Compound explainer · 15 min read

What is SS-31?

Written by [author]. Reviewed by [reviewer].

Updated . How we research and review.

Short answer

SS-31 (elamipretide) is a synthetic four-residue peptide, D-Arg-Dmt-Lys-Phe-NH2, that concentrates in the inner mitochondrial membrane and binds the phospholipid cardiolipin. [1][2] It came out of Hazel Szeto's laboratory at Weill Cornell. [3] Its randomised human trials mostly missed their primary endpoints, [4] and in September 2025 the USA granted it accelerated approval for Barth syndrome. [5]

What is SS-31?

SS-31 is a synthetic, cell-permeable tetrapeptide that belongs to the Szeto-Schiller (SS) peptides, a family designed to target the inner mitochondrial membrane. [10] Its international non-proprietary name is elamipretide. [1] Nothing in the body produces it. It entered clinical development with a commercial sponsor, Stealth, in 2010 as its acetate salt, the form the code MTP-131 refers to. [3]

Three facts shape everything below. SS-31 is small, at 639.8 g/mol. [1] It goes to one place in the cell, the inner mitochondrial membrane. And almost all of its clinical record comes from one sponsor's development programme. Research-grade SS-31 in 10mg vials is in stock with a batch certificate.

How does SS-31 work?

SS-31 works, as studied, by concentrating in the inner mitochondrial membrane and binding cardiolipin, a phospholipid found only there. A 2013 paper describes SS peptides crossing the cell membrane and concentrating more than 1000-fold in the inner mitochondrial membrane independently of mitochondrial membrane potential. [11] Its inventors report the same potential-independent uptake for the parent peptide SS-02, in contrast with lipophilic cations such as MitoQ. [3]

Using a fluorescent analogue of SS-31, Birk and colleagues reported high-affinity binding to cardiolipin in 2013, and found that the SS-31 and cardiolipin complex inhibited cytochrome c peroxidase activity. [2] A 2014 review sets out the proposed chain of events: [10]

  1. Cardiolipin organises the respiratory complexes into supercomplexes and shapes the cristae.
  2. The interaction between cardiolipin and cytochrome c decides whether cytochrome c acts as an electron carrier or as a peroxidase.
  3. SS-31 binds cardiolipin through electrostatic and hydrophobic interactions and, in the authors' account, keeps cytochrome c in its electron-carrying role.

A 2020 biophysics study from the University of Connecticut found that SS-31 sits in the membrane's interfacial region and changes the surface electrostatics of model and mitochondrial membranes. [12] A 2020 study in aged mice and rats reported that SS-31 associated with the adenine nucleotide translocase ANT1 and the mitochondrial ATP synthasome. [13]

Most of this mechanism work involves the compound's inventor. The 2020 membrane paper states that Szeto invented the peptides and founded Stealth BioTherapeutics, and that she has financial interests in the company. [12]

What is the structure of SS-31?

SS-31 is a linear tetrapeptide with an amidated C-terminus: D-arginine, 2',6'-dimethyltyrosine, lysine, phenylalanine amide. Its inventors' structure table gives it as H-d-Arg-Dmt-Lys-Phe-NH2. [3]

FieldValueSource
NameElamipretide (INN); SS-31PubChem
CAS number736992-21-5PubChem
PubChem CID11764719PubChem
UNII87GWG91S09PubChem
Molecular formulaC32H49N9O5PubChem
Molecular weight639.8 g/molPubChem
Exact mass639.3857 DaPubChem
Length4 residuesInventors' structure table
SequenceH-D-Arg-Dmt-Lys-Phe-NH2 (one-letter: r-[Dmt]-K-F-NH2)Inventors' structure table
Non-coded residuesD-Arg at position 1; Dmt (2',6'-dimethyltyrosine) at position 2Inventors' structure table
C-terminusAmidePubChem IUPAC name
Development codeMTP-131 (acetate salt)Inventors' 2014 review

The identifiers come from PubChem [1] and the sequence and salt form from the inventors' 2014 review. [3] We checked each value on 29 September 2026.

SS-31 has a sequence twin. SS-02, also called [Dmt1]DALDA, is H-Dmt-d-Arg-Phe-Lys-NH2: the same four residues in a different order. [3] The two therefore share the formula C32H49N9O5 and the same mass, so a mass spectrometry result matching 639.8 g/mol confirms composition, and the HPLC trace and the lab's identity method speak to the rest.

The 2004 paper that introduced this peptide class describes a motif of alternating aromatic and basic residues, with dimethyltyrosine providing the scavenging properties; analogues without Dmt did not inhibit mitochondrial ROS generation. [14]

What has research on SS-31 examined?

Research on SS-31 runs from cell and animal models of mitochondrial injury and ageing to randomised human trials in rare mitochondrial disease, heart disease and eye disease. The preclinical record is broad and mostly positive. The controlled human record is mostly negative on primary endpoints.

Laboratory and animal studies:

YearStudy (PMID)ModelReported finding
2004Zhao et al. (15178689)Neuronal cells, isolated mitochondria, ex vivo heartSS peptides concentrated 1000-fold in the inner mitochondrial membrane and reduced ROS and cell death after oxidative challenge [14]
2013Birk et al. (23813215)Rat kidney ischaemia; fluorescent analogueHigh-affinity cardiolipin binding; cristae protected during renal ischaemia [2]
2013Siegel et al. (23692570)Old (27-month) and young (5-month) miceAge-related declines in mitochondrial ATP production reversed one hour after a single treatment; no observable effect on young muscle [11]
2020Mitchell et al. (32273339)Model and mitochondrial membranesPartitioned into the membrane interface and modulated surface electrostatics [12]
2020Zhang et al. (33319746)Naturally aged mice and ratsPrevented age-related excess proton entry; the authors report substantial reversal of diastolic dysfunction [13]
2022Mitchell et al. (35913044)NMR, molecular dynamics, cell cultureSS-31 was the only one of four analogues that did not form a compact reverse turn when membrane bound [15]

Randomised and open-label human trials:

YearTrial (PMID)DesignWho was studiedReported finding
2016EMBRACE STEMI (26586786)Phase 2a, placebo controlledAdults with first anterior STEMI undergoing PCINo significant reduction in infarct size: CK-MB area under the curve 5785 ng h/mL on placebo, 5570 on SS-31 [6]
2017Daubert et al. (29217757)Placebo controlled, single 4-hour infusion36 adults with HFrEF (ejection fraction 35% or less)Highest of three cohorts: LVEDV -18 mL and LVESV -14 mL against placebo at end of infusion [16]
2020PROGRESS-HF (32068002)Phase 2, placebo controlled, 28 days71 adults with HFrEFChange in LVESV at week 4 not significantly different from placebo [17]
2020MMPOWER-2 (32096613)Crossover, 4-week periods30 adults with primary mitochondrial myopathy6-minute walk difference 19.8 m (P = 0.0833), primary endpoint not met; fatigue scores lower than placebo (P = 0.0006) [7]
2021TAZPOWER (33077895)Phase 2/3 crossover, then open label12 people with Barth syndromeNeither primary endpoint met in the randomised part; 6-minute walk +95.9 m at 36 weeks open label [18]
2023MMPOWER-3 (37268435)Phase 3, placebo controlled, 24 weeks218 adults with primary mitochondrial myopathyPrimary endpoints not met; 6-minute walk difference -3.2 m (p = 0.69) [4]
2024TAZPOWER extension (38602181)Open label, no control, 168 weeks10 entered; 8 reached week 168Cumulative 96.1 m 6-minute walk change from extension baseline [9]
2024LHON trial (37923251)Phase 2, vehicle controlled, eye drops12 adults with Leber hereditary optic neuropathyVisual acuity change not significantly different from vehicle eyes [19]
2024ReCLAIM-2 (39605874)Phase 2, placebo controlled, 48 weeks176 adults with dry AMD and geographic atrophyPrimary endpoints not met; progression of ellipsoid zone loss 43% lower than placebo (nominal P = 0.0034) [8]

The Daubert total is our arithmetic: three cohorts of 8 plus 12 on placebo. Every finding above is what a trial reported for its own population using the sponsor's pharmaceutical product.

The regulatory end point came in 2025. A 2026 review in Drugs reports that elamipretide received accelerated approval in the USA in September 2025 for muscle strength in adult and paediatric patients with Barth syndrome. [5] A second review adds that the approval requires a confirmatory trial. [20] The Drugs review also lists phase 3 development in dry age-related macular degeneration and mitochondrial myopathies. [5]

What does the SS-31 evidence not show?

The SS-31 evidence does not show consistent benefit in controlled human trials. Seven of the randomised trials above missed their primary efficacy endpoints, including the phase 3 trial MMPOWER-3, where the authors classed the result as Class I evidence of no improvement in walk distance or fatigue at 24 weeks. [4]

Five further limits are worth stating plainly.

  1. The positive Barth syndrome data are uncontrolled. The 168-week result comes from an open-label extension with no placebo group, which 10 patients entered and 8 completed. [9] The randomised part of the same trial met neither primary endpoint. [18]
  2. Independence is limited. Stealth BioTherapeutics employees are authors on the TAZPOWER papers and MMPOWER-3. [18][4] The inventor founded the company and holds financial interests in it. [12]
  3. The ageing data come from rodents. The age-reversal findings in the research table are from mice and rats. [11][13] No trial reviewed here tested SS-31 on ageing itself in people.
  4. The approval is narrow and conditional. It covers one ultra-rare disease in one country, and it was granted on an accelerated basis with a confirmatory trial required. [5][20]
  5. The trials used the sponsor's product. Purity, identity and peptide content of a research vial are separate questions, and a batch certificate answers them.

What adverse events have studies of SS-31 reported?

Studies of SS-31 most often reported reactions at the site where the study drug was given, mostly rated mild. In MMPOWER-2, these site reactions were the most commonly reported adverse events with elamipretide, at 80%, the majority mild, and no serious adverse events or deaths were reported. [7]

The other trials recorded these events:

  • Primary mitochondrial myopathy (MMPOWER-3, 218 adults, 24 weeks): the authors report that most adverse events were mild to moderate in severity. [4] The abstract gives no percentages.
  • Barth syndrome extension (10 patients, up to 168 weeks): site reactions were the most common adverse events. [9]
  • Dry AMD (ReCLAIM-2, 176 adults, 48 weeks): adverse events were reported in 86% of the elamipretide group and 71% of the placebo group. The most common were site reactions, including itching, pain, bruising and redness. [8]
  • Leber hereditary optic neuropathy (12 adults, eye drops): most adverse events were mild to moderate and resolved spontaneously, with no serious adverse events reported. [19]
  • Heart failure, single infusion (36 adults): no serious adverse events; blood pressure and heart rate stayed stable in all cohorts. [16]
  • Heart failure, 28 days (PROGRESS-HF, 71 adults): rates of study drug-related adverse events were similar across the three groups. [17]

These are clinical-trial observations in specific patient populations. Most abstracts give no adverse-event percentages, and exposure ran from a single infusion to 168 weeks.

Is SS-31 approved or scheduled in Australia?

SS-31 is not named in the Poisons Standard. We searched the June 2026 instrument (F2026L00633), which commenced on 1 June 2026, for elamipretide, SS-31 and MTP-131 and found no entry in any schedule or appendix. [21] The only regulatory approval reported in the literature reviewed here is the US accelerated approval of September 2025. [5]

For sport, SS-31 is not named on the WADA 2026 Prohibited List, which took effect on 1 January 2026. [22] The list's S0 class prohibits at all times any pharmacological substance not covered elsewhere on the List and with no current approval by any governmental regulatory health authority for human therapeutic use. Elamipretide has held a US approval since September 2025. [5] WADA revises the List every year, so check the current edition before relying on this.

MOTS-c is a different case: WADA names it under S4.4.1 as an AMPK activator. [22] Our guide to Australian peptide law and the Poisons Standard explains what each schedule means and why status is set compound by compound.

How does SS-31 compare with MOTS-c and NAD+?

SS-31 is a synthetic four-residue peptide that binds cardiolipin, MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, and NAD+ is a coenzyme with no amino acids at all. All three are studied in mitochondrial research.

FeatureSS-31MOTS-cNAD+
What it isSynthetic tetrapeptideMitochondrial-derived peptideDinucleotide coenzyme
Natural or syntheticSynthetic, with two non-coded residuesEncoded in the mitochondrial 12S rRNAPresent in all living cells
Length4 residues16 amino acidsNo amino acids
Molecular weight639.8 g/mol2174.6 g/mol663.4 g/mol
Studied targetCardiolipin, inner mitochondrial membraneInsulin sensitivity and metabolic signallingRedox reactions
Human evidenceRandomised trials; US approval in 2025Measures of the body's own MOTS-c; no controlled trials giving it to people identifiedMainly trials of oral precursors
WADA 2026Not namedNamed under S4.4.1Not named

The molecular weights come from PubChem. [1][23][24] MOTS-c was first described in 2015 as a 16-amino-acid peptide encoded by a short open reading frame in the mitochondrial 12S rRNA. [25] The other rows come from our own compound checks of 29 September 2026. Our explainers on what MOTS-c is and what NAD+ is cover each in full, and all three sit in our longevity research peptides range.

How is SS-31 stored and handled in the lab?

No published stability study covers lyophilised research-grade SS-31, so general peptide guidance is the reference point. Bachem's handling guide recommends storing lyophilised peptide in a tightly closed container below -15°C for longer storage, with lower temperatures preferred, and says a refrigerator at 4°C suits short-term use. [26]

StagePublished guidanceSource
Lyophilised, long termTightly closed container below -15°C; -50°C or lower preferred for long-term storageBachem
Lyophilised, short termRefrigerator at 4°C; may ship at room temperatureBachem
Before openingPeptides are hygroscopic; let the container reach ambient temperature in a desiccator firstBachem
In solutionAliquot and keep frozen below -15°C; long-term storage in solution is not recommendedBachem

The same guide says peptides containing Asn, Gln, Met, Cys or Trp have limited shelf lives. [26] SS-31 contains none of those five residues, which is our reading of its sequence. It is still a peptide, so the guidance above applies in full.

On solvents, the clearest primary detail comes from the 2013 aged-mouse study, which dissolved SS-31 in isotonic saline at a concentration of 0.3 mg/mL. [11] SS-31 is also a basic peptide by Bachem's definition: it carries three basic groups (the N-terminal amine, arginine and lysine), no acidic residue and an amidated C-terminus. Bachem notes that peptides with a large share of Arg and Lys residues tend to be soluble at neutral pH, and names PBS at pH 7.0 to 7.4 as the safest diluent for basic peptides where 1 mg/mL or less is enough. [26]

We stock BAC Water in 3ml vials for A$8 for laboratory reconstitution. Record the solvent and the resulting mg per mL concentration on the vial label. Our peptide storage guide covers temperatures, light, moisture and labelling for lyophilised and reconstituted peptides.

Where can researchers buy SS-31 in Australia?

Peptides Collective sells SS-31 for laboratory research use only, as lyophilised powder in 10mg vials for A$98. Stock ships from Western Australia with tracking.

Every batch is tested by an independent lab before it goes on sale. The certificate reports purity by HPLC and identity by mass spectrometry, and it is published under the batch number printed on the vial. You can search the certificate of analysis library by that batch number and match the report to the vial in your hand.

Read the certificate against the structure table. The identity result should correspond to a peptide of 639.8 g/mol. A spectrum reported as the protonated ion sits about one mass unit higher, near 640.4. Clinical development used an acetate salt, and a salt form adds counter-ion weight to the powder, which is one reason net peptide content is reported separately from purity. Our guide on how to read a peptide certificate of analysis explains the HPLC trace, the mass spectrum and net peptide content. The SS-31 product page links the certificate for the current batch.

Bottom line

SS-31 is a four-residue synthetic peptide that concentrates in the inner mitochondrial membrane and binds cardiolipin. Its preclinical record is broad, its controlled human trials mostly missed their primary endpoints, and its one approval is a conditional US approval for Barth syndrome. In Australia it is not named in the June 2026 Poisons Standard, and WADA's 2026 List does not name it. For a research vial, the batch certificate is the evidence that settles what is in the vial.

Questions

Can SS-31 reverse aging?

No human study has tested that. The ageing data come from rodents: a 2013 study reported that age-related declines in mitochondrial ATP production in 27-month-old mice reversed an hour after a single treatment, and a 2020 study in aged mice and rats reported substantial reversal of diastolic dysfunction. Both are animal results. None of the human trials reviewed here measured ageing as an outcome.

Where can I buy SS-31 peptide online?

Peptides Collective sells SS-31 online for laboratory research use only, in 10mg lyophilised vials for A$98, dispatched from Western Australia with tracking. Each batch is tested by an independent lab, and its certificate is published under the batch number printed on the vial, so you can check the report before you order.

What is the main difference between MOTS-c and SS-31 peptides?

SS-31 is a synthetic four-residue peptide that binds cardiolipin in the inner mitochondrial membrane. MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial 12S rRNA and studied for metabolic signalling. Their evidence also differs: SS-31 has randomised human trials, while MOTS-c research is mainly in cells and mice. WADA names MOTS-c under S4.4.1 and does not name SS-31.

Is SS-31 a prescription medicine in Australia?

SS-31 is not listed in Schedule 4 or any other schedule. It has no entry in the June 2026 Poisons Standard, which commenced on 1 June 2026. The only regulatory approval reported in the literature reviewed here is the September 2025 US accelerated approval for Barth syndrome. Peptides Collective sells SS-31 for laboratory research use only.

Is SS-31 banned in sport?

SS-31 is not named on the WADA 2026 Prohibited List, effective 1 January 2026. The S0 class covers substances with no current governmental approval for human therapeutic use, and elamipretide has held a US approval since September 2025. WADA revises the List every year, so check the current edition.

What is the half-life of SS-31?

The elimination half-life of SS-31 was about 4 hours in phase I studies in healthy volunteers, and about 2 hours in rats, dogs and monkeys, according to the inventors' 2014 review. The same review reports hydrolysis from the C-terminus into tripeptide and dipeptide fragments, with the parent peptide and its fragments excreted by the kidneys within 48 hours.

What is the molecular weight of SS-31?

PubChem lists the molecular weight of SS-31 as 639.8 g/mol for the formula C32H49N9O5, with an exact mass of 639.3857 Da. Clinical development used the acetate salt, and the counter-ion adds weight to the powder without adding peptide, so check which form a certificate describes.

How should SS-31 be stored?

Store lyophilised SS-31 sealed and frozen. Bachem's general peptide guidance is below -15°C in a tightly closed container for longer storage, 4°C for short-term use, and warming the container to ambient temperature in a desiccator before opening. No published stability study covers research-grade SS-31.

Which solvent is used to reconstitute SS-31?

Published animal work dissolved SS-31 in isotonic saline at 0.3 mg/mL. As a basic peptide rich in arginine and lysine, it fits Bachem's guidance that such peptides tend to dissolve at neutral pH, with PBS at pH 7.0 to 7.4 as the safest diluent at 1 mg/mL or less. Peptides Collective stocks BAC Water for laboratory reconstitution.

Where does the SS-31 sequence come from?

The SS-31 sequence comes from SS-02, also called [Dmt1]DALDA, a synthetic opioid peptide Szeto's group was studying. They found SS-02 entered cells readily, then designed analogues, including SS-31, that target the inner mitochondrial membrane with negligible opioid receptor affinity. SS-31 uses the same four residues as SS-02 in a new order.

Who discovered SS-31?

SS-31 came from Hazel H. Szeto's research group at Weill Cornell Medical College, and the family is known as the Szeto-Schiller peptides. Peter W. Schiller co-authored the 2004 paper introducing the class. Szeto describes the discovery as serendipitous. The Cornell Research Foundation licensed the technology to Stealth BioTherapeutics.

Is SS-31 a peptide or a small molecule?

SS-31 is a peptide: four residues joined by peptide bonds, with a C-terminal amide and a molecular weight of 639.8 g/mol. Its inventors also call the SS peptides a new class of small molecules, since the family is small and enters cells without transporters. It is a tetrapeptide of small-molecule size.

What is the CAS number for SS-31?

The CAS number for SS-31 (elamipretide) is 736992-21-5. Its PubChem compound ID is 11764719 and its UNII code is 87GWG91S09. The same CAS number covers the names elamipretide, SS-31 and MTP-131 in PubChem's synonym list.

Sources

  1. 1. PubChem, NCBI
  2. 2. Birk AV et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol, 2013.
  3. 3. Szeto HH et al. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clin Pharmacol Ther, 2014.
  4. 4. Karaa A et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology, 2023.
  5. 5. Shirley M et al. Elamipretide: First Approval. Drugs, 2026.
  6. 6. Gibson CM et al. EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Eur Heart J, 2016.
  7. 7. Karaa A et al. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. J Cachexia Sarcopenia Muscle, 2020.
  8. 8. Ehlers JP et al. ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation. Ophthalmol Sci, 2025.
  9. 9. Thompson WR et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med, 2024.
  10. 10. Szeto HH et al. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol, 2014.
  11. 11. Siegel MP et al. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell, 2013.
  12. 12. 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.
  13. 13. Zhang H et al. Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte. Elife, 2020.
  14. 14. Zhao K et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem, 2004.
  15. 15. Mitchell W et al. Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds. Elife, 2022.
  16. 16. Daubert MA et al. Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. Circ Heart Fail, 2017.
  17. 17. Butler J et al. Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. J Card Fail, 2020.
  18. 18. Reid Thompson W et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genet Med, 2021.
  19. 19. Karanjia R et al. Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial. Ophthalmology, 2024.
  20. 20. Zhao C et al. Elamipretide: The first cardiolipin-directed mitochondrial therapeutic for Barth syndrome approved under accelerated approval. Drug Discov Ther, 2026.
  21. 21. Federal Register of Legislation, Poisons Standard June 2026 (F2026L00633)
  22. 22. World Anti-Doping Agency, 2026 Prohibited List
  23. 23. PubChem, NCBI
  24. 24. PubChem, NCBI
  25. 25. Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 2015.
  26. 26. Bachem