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SS-31

SS-31 (Elamipretide, MTP-131, CAS 736992-21-5): a mitochondria-targeted tetrapeptide for research in Mexico. Mechanism, evidence and technical data.

SS-31: Scientific Profile

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SS-31 (Elamipretide; development code MTP-131; CAS 736992-21-5) is an aromatic-cationic tetrapeptide targeting the inner mitochondrial membrane, with the sequence D-Arg-Dmt-Lys-Phe-NH2. In research studies it binds to cardiolipin to stabilize mitochondrial cristae and improve the efficiency of the electron transport chain. Material intended exclusively for research use.

SS-31, also known by its international name elamipretide and by the development code MTP-131 (CAS 736992-21-5; molecular formula C32H49N9O5; molecular weight ~639.8 g/mol), is a synthetic tetrapeptide classified within the anti-aging category for its link to mitochondrial biology. It belongs to the family of aromatic-cationic peptides known as Szeto-Schiller (SS) peptides, originally developed by the groups of Hazel Szeto and Peter Schiller. Its sequence, D-Arg-Dmt-Lys-Phe-NH2, includes the non-standard amino acid 2',6'-dimethyltyrosine (Dmt) and a D-arginine residue, a design that confers resistance to degradation by peptidases and a characteristic alternation of aromatic and basic residues. This structure is the basis of its most distinctive property: the ability to concentrate selectively in the inner mitochondrial membrane without depending on the membrane potential, unlike other cationic compounds that accumulate only when the potential is intact.

From a structural standpoint, SS-31 is a small, stable, water-soluble peptide whose net positive charge at physiological pH and its two aromatic rings allow it to cross membranes and partition into the inner lipid bilayer of the mitochondrion. Once there, preclinical research has documented that the compound interacts preferentially with cardiolipin, an anionic phospholipid exclusive to the inner mitochondrial membrane that is essential for the organization of the cristae and for the correct assembly and function of the electron transport chain complexes. This affinity for cardiolipin is the central axis around which the proposed mechanism of the peptide is articulated.

As for the mechanism of action, research models suggest that SS-31, by associating with cardiolipin, helps preserve the architecture of the mitochondrial cristae and the integrity of the respiratory supercomplexes. By stabilizing these structures, an improvement in the efficiency of electron transport, an increase in ATP production, and a reduction in the electron leak that gives rise to reactive oxygen species (ROS) have been observed in experimental systems. Unlike a classical antioxidant that neutralizes radicals already formed, the predominant view is that SS-31 acts "upstream," decreasing ROS generation by optimizing the coupling of oxidative phosphorylation. In models of ischemia-reperfusion injury, age-associated mitochondrial dysfunction, and various myopathies, this stabilization has been correlated with reduced opening of the mitochondrial permeability transition pore and with the preservation of cellular function. It is important to emphasize that these are findings from preclinical research and from ongoing or completed clinical trials, not claims of established therapeutic efficacy.

The documented research applications of SS-31/elamipretide are unusually broad for a peptide of this size, in large part because mitochondrial dysfunction is a common denominator of many processes. In the cardiovascular field it has been explored in models of heart failure and of ischemia-reperfusion injury. In the area of primary mitochondrial diseases, elamipretide has been the subject of clinical development programs sponsored by Stealth BioTherapeutics, including studies in primary mitochondrial myopathy (the MMPOWER series of trials) and in Barth syndrome (the TAZPOWER trial), a tafazzin-related disorder linked to cardiolipin abnormalities. In ophthalmology it has been investigated in dry-type age-related macular degeneration and in other retinopathies (the ReCLAIM program), given the high mitochondrial component of the retinal pigment epithelium. Additionally, basic research on aging has used SS-31 to study the recovery of skeletal muscle function, exercise capacity and renal physiology in models of senescence, which supports its placement within the anti-aging category in this catalog.

Regarding the level of evidence, SS-31 occupies an intermediate and relatively robust position compared with many research peptides: there is a substantial body of peer-reviewed preclinical literature and, notably, several human clinical trials conducted by its developer. Nevertheless, it is essential to remain honest about the results: some of these clinical trials did not meet their primary endpoints (for example, certain analyses in primary mitochondrial myopathy and in Barth syndrome yielded mixed or negative results on the prespecified objectives), while others showed signals of benefit on secondary objectives. Therefore, although the molecule is highly characterized at the chemical and mechanistic level and has clinical data, it should not be presented as a compound of demonstrated efficacy or with broadly approved therapeutic use. Its value to the researcher lies precisely in being a well-defined tool for interrogating the biology of cardiolipin and mitochondrial bioenergetics.

In summary, SS-31 (elamipretide, MTP-131) is a mitochondria-targeted tetrapeptide, chemically well characterized, whose proposed mechanism revolves around binding to cardiolipin and stabilization of the inner mitochondrial membrane, with the consequent improvement of bioenergetic efficiency and reduction of ROS in experimental systems. It has a broad preclinical evidence base and clinical-trial data with heterogeneous results. All the material described here is intended exclusively for laboratory research use and its handling must be carried out in accordance with good practices of the scientific setting.

Mechanism of action

SS-31 is an aromatic-cationic peptide that partitions into the inner mitochondrial membrane independently of membrane potential, owing to its net positive charge and its aromatic residues (including 2',6'-dimethyltyrosine). Once in the inner membrane, preclinical research describes a preferential association with cardiolipin, an anionic phospholipid essential for cristae curvature and for the assembly of the complexes and supercomplexes of the electron transport chain.

By interacting with cardiolipin, it has been proposed that SS-31 preserves the architecture of the cristae and the integrity of the respiratory supercomplexes. In experimental systems this translates into more efficient electron transport, greater ATP synthesis, and less electron leakage toward oxygen, thus decreasing the production of reactive oxygen species (ROS) at their origin instead of neutralizing them once formed.

This stabilizing effect has been correlated in research models with a reduction in the opening of the mitochondrial permeability transition pore, attenuation of oxidative stress, and preservation of cellular function in contexts of ischemia-reperfusion, age-associated mitochondrial dysfunction, and myopathies. These are mechanisms documented in preclinical research and in clinical trials, not established therapeutic actions.

Mechanism summary

SS-31 concentrates in the inner mitochondrial membrane and binds to cardiolipin, stabilizing the cristae and the respiratory supercomplexes; in research models this improves the efficiency of electron transport and reduces the generation of reactive oxygen species.

Clinical Studies (5)

  • SS-31@Fer-1 Alleviates ferroptosis in hypoxia/reoxygenation cardiomyocytes via mitochondrial targeting (Zheng H et al. · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025) PMID 39848110.
  • Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice (Zhao W et al. · Journal of neuroinflammation · 2019) PMID 31747905.
  • Protection of mitochondria prevents high-fat diet-induced glomerulopathy and proximal tubular injury (Szeto, et al. · Kidney International · 2016) PMID 27519664.
  • Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential (Tung, et al. · International Journal of Molecular Sciences · 2025) PMID 39940712.
  • Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome (Hornby, et al. · Orphanet Journal of Rare Diseases · 2022) PMID 36056411.

Warnings

SS-31 is a compound exclusively for research use (RUO); the following warnings and handling considerations apply to its use in the laboratory:

  • Material intended exclusively for laboratory research use
  • The results of clinical trials have been heterogeneous and demonstrated therapeutic efficacy should not be assumed
  • Must be handled only by qualified personnel in a research environment
  • Models with known hypersensitivity to SS-31 (elamipretide)
  • The results of clinical trials have been heterogeneous: do not assume demonstrated therapeutic efficacy
  • Pregnant or lactating models (insufficient data)

Technical data

CAS
736992-21-5
Molecular formula
C32H49N9O5
Molecular weight
639.8 Da
Compound type
peptide
Storage
Lyophilized: -20°C; reconstituted: 2-8°C protected from light
Light-sensitive
No

Available for research

SS-31 is available as a research-use-only (RUO) reagent with HPLC-verified purity and a per-batch COA:

Frequently asked questions about SS-31

What is SS-31?

SS-31 (Elamipretide; development code MTP-131; CAS 736992-21-5) is an aromatic-cationic tetrapeptide targeting the inner mitochondrial membrane, with the sequence D-Arg-Dmt-Lys-Phe-NH2. In research studies it binds to cardiolipin to stabilize the mitochondrial cristae and improve the efficiency of the chain of…

What is the mechanism of action of SS-31?

SS-31 concentrates in the inner mitochondrial membrane and binds to cardiolipin, stabilizing the cristae and the respiratory supercomplexes; in research models this improves the efficiency of electron transport and reduces the generation of reactive oxygen species.

What is SS-31 researched for?

In preclinical research, SS-31 is studied mainly in: Research on bioenergetics and mitochondrial function; Models of oxidative stress and reduction of reactive oxygen species; Studies on stabilization of cristae and cardiolipin. Material exclusively for scientific research.

What are the chemical properties of SS-31?

Molecular formula C32H49N9O5; molecular weight 639.8 Da; CAS number 736992-21-5.

How is SS-31 stored?

Storage conditions: Lyophilized: -20°C; reconstituted: 2-8°C protected from light.

What routes of administration are studied for SS-31?

In research models the following are described: Reconstitution in bacteriostatic water, Subcutaneous (in research models), Intravenous (in research protocols). Use is exclusively for scientific research.

See also