Longevity & Cellular

SS-31 (Elamipretide)

Mitochondria-targeted tetrapeptide

A mitochondria-targeting tetrapeptide studied in cellular-energy and longevity research.

Also referenced as: Elamipretide, MTP-131

4 aa

Overview

SS-31 (elamipretide, also known as MTP-131 or Bendavia) is a synthetic, cell-permeable, mitochondria-targeted tetrapeptide developed from the Szeto-Schiller (SS) family of aromatic-cationic peptides. It is one of the most studied members of that peptide series.

At a glance

ClassMitochondria-targeted tetrapeptide

CategoryLongevity & Cellular

SequenceD-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2 (D-Arg-Dmt-Lys-Phe-NH2)

Chain length4 amino acids

Molecular weight639.8 g/mol (approx.)

Typical formLyophilized powder

AliasesElamipretide, MTP-131

Use designationResearch / in-vitro only

Regulatory statusSS-31/elamipretide is an investigational drug studied in clinical trials; it is not broadly FDA- or EMA-approved. Research and educational information only, not medical advice.

What SS-31 (Elamipretide) does

SS-31, known clinically as elamipretide, is a synthetic mitochondria-targeted tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine). Its defining action is to selectively concentrate in the inner mitochondrial membrane, where it binds cardiolipin, a signature phospholipid essential for the structure of mitochondrial cristae and for the proper assembly and function of the electron-transport-chain complexes. Because it accumulates in the inner membrane at concentrations reported to be over 1,000-fold higher than in cytoplasm, it acts almost exclusively at the organelle that produces the cell's energy.

By stabilizing cardiolipin, SS-31 helps preserve cristae architecture and cardiolipin-dependent respiratory-complex assembly, which in studies improves electron-transport efficiency and ATP output while reducing electron leak and reactive-oxygen-species generation. Downstream, the reduction in oxidative stress has been linked to NRF2-mediated antioxidant gene expression and dampened NF-kB inflammatory signaling, and it influences expression of nuclear-encoded mitochondrial genes. It is therefore best described as a mitochondrial 'protectant' that restores bioenergetic quality in dysfunctional mitochondria rather than as a stimulant.

SS-31 is the most clinically advanced peptide in this set. It has been tested in humans across primary mitochondrial myopathy, dry age-related macular degeneration, heart failure, and ischemia-reperfusion injury, with mixed results, notably a pivotal Phase 3 primary-mitochondrial-myopathy trial that missed its primary endpoints in the overall population. In September 2025 elamipretide received FDA approval for Barth syndrome, the first approval of any mitochondria-targeted peptide. Its broader anti-aging applications remain investigational, but the underlying cardiolipin-targeting mechanism is unusually well documented.

Effects reported in research

Selectively binds cardiolipin in the inner mitochondrial membrane, concentrating there at >1,000-fold cytoplasmic levels (mechanistic).
Stabilizes mitochondrial cristae structure and cardiolipin-dependent electron-transport-chain complex assembly.
Improves electron-transport efficiency and ATP production in dysfunctional mitochondria in preclinical models.
Reduces mitochondrial reactive-oxygen-species generation and electron leak, lowering oxidative stress.
Reduced oxidative load has been linked to NRF2 antioxidant gene activation and dampened NF-kB inflammatory signaling (preclinical).
Ameliorated cardiac mitochondrial morphology and restored defective mitophagy in a murine Barth-syndrome model (preclinical).
In humans, tested across primary mitochondrial myopathy, dry AMD, and heart failure with mixed results; the pivotal Phase 3 myopathy trial missed its primary endpoints.
FDA-approved in September 2025 as elamipretide for Barth syndrome, the first mitochondria-targeted peptide ever approved; broader anti-aging uses remain investigational.

Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.

Mechanism of action

SS-31/elamipretide selectively concentrates in the inner mitochondrial membrane, where it is reported to bind the phospholipid cardiolipin. By associating with cardiolipin, it is proposed to stabilize the structure of the inner membrane and cristae, support electron transport chain organization and efficiency, and reduce excessive reactive oxygen species production. These actions are intended to improve mitochondrial bioenergetics under conditions of mitochondrial dysfunction.

Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.

What it's studied for

Research contexts in which SS-31 (Elamipretide) appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.

Key characteristics

Aromatic-cationic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2)
Targets the inner mitochondrial membrane and binds cardiolipin
Aims to stabilize cristae and improve bioenergetics, reducing ROS
Investigational drug (elamipretide) evaluated in human clinical trials
Studied in mitochondrial diseases, heart failure, and Barth syndrome
Distinct from the naturally occurring mitochondrial peptide humanin

Reported research dosing reference only

Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. SS-31 (Elamipretide) is a research compound.

Reported dosing comes from clinical trials of elamipretide using either slow IV infusion across a dose range or a fixed subcutaneous daily dose. These are reference figures for research context only, not dosing guidance for humans.

Clinical trial reference: 40 mg subcutaneously once daily (e.g. TAZPOWER / Barth syndrome trials)
IV infusion reference: ~0.01-0.25 mg/kg/hour over several hours in human studies

Reported frequencyOnce daily for the subcutaneous protocol; infusion-based for IV studies

ReconstitutionSupplied lyophilized; reconstituted with bacteriostatic water or saline for subcutaneous injection

Elamipretide has a relatively short plasma half-life, supporting once-daily or infusion-based dosing in trials rather than infrequent administration.

How it compares

SS-31 is a synthetic mitochondria-targeting tetrapeptide that physically localizes to the inner membrane and binds cardiolipin, and unlike most peptides here it has advanced into human clinical trials as elamipretide.

Commonly studied alongside

Compounds frequently researched together with SS-31 (Elamipretide) in the literature. Cross-referenced for research context — not a usage or combination recommendation.

MOTS-cBoth are mitochondria-focused compounds studied together in mitochondrial-function and metabolic-aging research.NAD+Complementary mitochondrial-bioenergetics targets, discussed together in mitochondrial-aging research.HumaninBoth relate to mitochondrial protection and are co-studied in mitochondrial-derived and mito-targeted peptide research.

Compare and calculate

Side-by-side pages for the pairings the literature already documents for SS-31 (Elamipretide), plus the unit-conversion reference for a reconstituted vial. Factual comparisons of documented characteristics — not a recommendation to combine or use any compound.

Handling & Stability

Lyophilized peptides are stored cold, protected from light, and reconstituted only at the time of intended in-vitro work.

Avoid repeated freeze-thaw cycles
Verify supplier lot and Certificate of Analysis
Follow institutional lab-safety protocols

Analytical & COA Concepts

Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:

Category Context

SS-31 (Elamipretide) sits in the Longevity & Cellular area of the PeptiDex library.

Research Supplier Listing

Where researchers source SS-31 (Elamipretide)

For researchers studying SS-31 (Elamipretide), third-party suppliers such as Practically Natty Peptides offer research-grade material, third-party tests every batch and provides Certificates of Analysis on request, and ship from the US.

View research-supplier listing →

Outbound link to a third-party research supplier. Inclusion does not constitute endorsement; all editorial content is developed independently.

Frequently asked questions

What is SS-31 (elamipretide)?

SS-31 (elamipretide, also known by the codes Bendavia and SS-31) is a mitochondria-targeted tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2, that concentrates in the inner mitochondrial membrane by binding cardiolipin. It is studied in models of mitochondrial dysfunction, heart failure, ischemia-reperfusion, and age-related bioenergetic decline.

How does SS-31 target mitochondria?

Its alternating cationic and aromatic residues give it strong affinity for cardiolipin, a phospholipid found almost exclusively on the inner mitochondrial membrane. By binding cardiolipin it is thought to stabilize cristae structure and improve electron-transport efficiency, reducing reactive oxygen species.

What is the sequence and molecular weight of SS-31?

SS-31 is the tetrapeptide D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2 (D-Arg-Dmt-Lys-Phe-NH2), with molecular formula C32H49N9O5 and a molecular weight of about 639.8 g/mol. The unusual dimethyltyrosine and C-terminal amide are defining features.

Is SS-31 / elamipretide an approved drug?

Elamipretide has been studied extensively in clinical trials (e.g. for Barth syndrome and mitochondrial myopathy) and has moved toward regulatory approval in that indication, but availability as an approved drug is limited and indication-specific. As a research chemical it should not be treated as a broadly approved therapy.

How is SS-31 administered in research and trials?

Clinical trials have used both intravenous infusion over a dose range and a fixed subcutaneous daily dose (e.g. 40 mg SC in mitochondrial-disease trials). The route and dose depend on the study design and target tissue.

Answers are educational summaries of research-literature context and do not constitute medical advice. See the Research Library, COA guide, and Storage & Handling guide for more.

References

Primary literature indexed in PubMed for SS-31 (Elamipretide). Listing a study records that it exists and is indexed — it is not a claim of efficacy, a therapeutic indication, or an endorsement of its conclusions. Much of this literature is preclinical (in-vitro or animal-model).

The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin J Am Soc Nephrol, 2013. PubMed 23813215
Mitochondrial protein interaction landscape of SS-31 Proc Natl Acad Sci U S A, 2020. PubMed 32554501
Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential Int J Mol Sci, 2025. PubMed 39940712

Each reference was checked against its PubMed record on 2026-07-28: the PMID resolves and the title, journal and year match. Where no indexed literature exists for a compound, PeptiDex says so rather than substituting a citation about a different molecule. See the editorial policy.