SS-31: Research, Handling and Batch Documentation

Identity and research status

Also referred to as

Elamipretide, Bendavia, MTP-131

Sequence

D-Arg-Dmt-Lys-Phe-NH2

Full residue names

D-arginine, 2',6'-dimethyl-L-tyrosine, L-lysine, L-phenylalanine amide

Molecular Formula (free base)

C32H49N9O5

Molecular Weight (free base)

639.8 g/mol

CAS Number

736992-21-5

PubChem CID

11764719

InChIKey

SFVLTCAESLKEHH-WKAQUBQDSA-N

Acetate salt

C34H53N9O7, 699.8 g/mol (PubChem CID 163336973)

Trihydrochloride salt

C32H52Cl3N9O5, 749.2 g/mol (PubChem CID 137528200)

Net charge at pH 7.4

3+

Compound class

Aromatic-cationic Szeto-Schiller tetrapeptide, mitochondria-targeted

Synonyms

Elamipretide, MTP-131, Bendavia, Forzinity

Appearance

White lyophilised powder

Solubility

Water soluble

CAS number

736992-21-5

Mechanism, in brief

SS-31 has no receptor. It is not a signalling peptide and nothing on the cell surface recognises it. Zhao and colleagues showed in 2004 that peptides built on this alternating aromatic and basic motif cross the plasma membrane without a carrier and then concentrate roughly 1000-fold in the inner mitochondrial membrane relative to the surrounding medium. In neuronal N2A cells they blocked tert-butylhydroperoxide toxicity with EC50 values in the nanomolar range, and in isolated mitochondria they prevented calcium-induced swelling and cytochrome c release. Analogues built without the dimethyltyrosine residue neither suppressed mitochondrial reactive oxygen species nor prevented myocardial stunning in the ex vivo heart, which is the first evidence that the aromatic residue is structural to the effect and not decorative.

1. Carrier-free membrane entry. The alternating aromatic and basic motif lets the peptide cross the plasma membrane without a transporter, which is unusual for a compound carrying a 3+ charge (Zhao, 2004).
2. Mitochondrial concentration. Accumulates roughly 1000-fold in the inner mitochondrial membrane relative to the surrounding medium, which is why effects are seen at nanomolar external concentrations.
3. Cardiolipin binding. Binds cardiolipin with high affinity through combined electrostatic and hydrophobic interactions, demonstrated with a polarity-sensitive fluorescent analogue (Birk, 2013).
4. Cytochrome c protection. The peptide and cardiolipin complex inhibits cytochrome c peroxidase activity by shielding the heme iron, preserving cytochrome c as an electron carrier rather than a lipid oxidant.
5. Cristae and supercomplex stabilisation. Cardiolipin is required for cristae curvature and for organising respiratory complexes into supercomplexes. Protecting it preserves membrane architecture and oxidative phosphorylation.
6. PLSCR3 dependence. A genome-wide CRISPR screen found phospholipid scramblase 3 to be necessary for the effect in kidney cells and in mice, a finding the cardiolipin model does not yet accommodate (Silvaroli, 2024).

The full research write-up, including the findings behind each claim and the model each came from, is on the SS-31 10mg 10mg page.

Vial sizes available

Every size of SS-31 Volta lists, in stock or not. Each is a separate catalogue page with its own batch number and specification table.

• SS-31 10mg 10mgBatch #: VPS310100
  In stock

Purity and batch documentation

Volta's release specification is >99% (HPLC). That is a threshold we set. >99% is the specification every batch is released to. The figure on a certificate is what a laboratory measured for one lot.

• SideChain Analytics reported 99.6% by HPLC-MS/MS on September 24, 2026.

  Covers the SS-31 10mg vial.

  Read the certificateVerify on lab's website (Verify on SideChain Analytics's website, opens in a new tab)

Research on SS-31

Handling and stability

Regulatory context

United States

FDA-approved (September 2025) as Forzinity for Barth syndrome — first FDA-approved mitochondria-targeted therapeutic. Accelerated approval pathway. FDA Fast Track and Orphan Drug designation.

European Union

Investigational. EMA Orphan Drug designation.

• the legal status of research peptides in Canada
• Health Canada's regulatory position

Primary sources

1. Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. Journal of Biological Chemistry (2004). doi:10.1074/jbc.M402999200
2. Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, Seshan SV, Pardee JD, Szeto HH. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology (2013). doi:10.1681/ASN.2012121216
3. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology (2014). doi:10.1111/bph.12461
4. Silvaroli JA, Bisunke B, Kim JY, et al.. Genome-Wide CRISPR Screen Identifies Phospholipid Scramblase 3 as the Biological Target of Mitoprotective Drug SS-31. Journal of the American Society of Nephrology (2024). doi:10.1681/ASN.0000000000000338
5. Sabbah HN, Alder NN, Sparagna GC, et al.. Contemporary insights into elamipretide's mitochondrial mechanism of action and therapeutic effects. Biomedicine & Pharmacotherapy (2025). doi:10.1016/j.biopha.2025.118056
6. Siegel MP, Kruse SE, Percival JM, et al.. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell (2013). doi:10.1111/acel.12102
7. Chiao YA, Zhang H, Sweetwyne M, et al.. Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. eLife (2020). doi:10.7554/eLife.55513
8. Gibson CM, Giugliano RP, Kloner RA, 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. European Heart Journal (2016). doi:10.1093/eurheartj/ehv597
9. Butler J, Khan MS, Anker SD, et al.. Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. Journal of Cardiac Failure (2020). doi:10.1016/j.cardfail.2020.02.001
10. Saad A, Herrmann SMS, Eirin A, et al.. Phase 2a Clinical Trial of Mitochondrial Protection (Elamipretide) During Stent Revascularization in Patients With Atherosclerotic Renal Artery Stenosis. Circulation: Cardiovascular Interventions (2017). doi:10.1161/CIRCINTERVENTIONS.117.005487
11. Karaa A, Haas R, Goldstein A, Vockley J, Weaver WD, Cohen BH. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology (2018). doi:10.1212/WNL.0000000000005255
12. Karaa A, Haas R, Goldstein A, Vockley J, Cohen BH. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. Journal of Cachexia, Sarcopenia and Muscle (2020). doi:10.1002/jcsm.12559
13. Karaa A, Bertini E, Carelli V, et al.. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology (2023). doi:10.1212/WNL.0000000000207402
14. Karaa A, Bertini E, Carelli V, et al.. Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial. Orphanet Journal of Rare Diseases (2024). doi:10.1186/s13023-024-03421-5
15. Reid Thompson W, Hornby B, Manuel R, Bradley E, Laux J, Carr J, Vernon HJ. 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. Genetics in Medicine (2021). doi:10.1038/s41436-020-01006-8
16. Thompson WR, Manuel R, Abbruscato A, et al.. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genetics in Medicine (2024). doi:10.1016/j.gim.2024.101138
17. Hornby B, Thompson WR, Almuqbil M, Manuel R, Abbruscato A, Carr J, Vernon HJ. Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome. Orphanet Journal of Rare Diseases (2022). doi:10.1186/s13023-022-02469-5
18. Ehlers JP, Hu A, Boyer D, 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. Ophthalmology Science (2025). doi:10.1016/j.xops.2024.100628
19. Karanjia R, Sadun AA. Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial. Ophthalmology (2024). doi:10.1016/j.ophtha.2023.10.033
20. Shirley M. Elamipretide: First Approval. Drugs (2026). doi:10.1007/s40265-025-02269-8
21. National Center for Biotechnology Information. Elamipretide, PubChem Compound Summary CID 11764719. PubChem (2026)
22. Stealth BioTherapeutics. NuPOWER: Phase 3 trial of elamipretide in primary mitochondrial disease from nuclear DNA mutations (NCT05162768). ClinicalTrials.gov (2024)