SS-31 10 mg

SS-31 (Elamipretide) — 10 mg

Purity: ≥98% (HPLC)
Form: lyophilized powder, 3 mL vial
Storage: −20 °C (before opening), +2…+8 °C (after reconstitution, no more than 28 days)
Verification: Janoshik Analytical (Czech Republic) — independent blind test of every batch
Synonyms: SS-31, Elamipretide, MTP-131, Bendavia

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Contents

1. What is SS-31?
2. Why SS-31 attracts researchers' attention
3. Peptide structure
4. Cardiolipin — the key to understanding SS-31
5. How SS-31 enters mitochondria
6. Clinical studies
7. SS-31 and aging
8. SS-31 and MOTS-C — two approaches to mitochondria
9. Sources

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1. What is SS-31?

SS-31 is a synthetic tetrapeptide developed by Hazel Szeto at Cornell University (Weill Medical College) in the early 2000s. The name "SS" comes from Szeto-Schiller, the surnames of its creators. It is the first peptide in its class capable of penetrating into mitochondria and stabilizing their inner membrane.

In clinical development, SS-31 is known as elamipretide. In 2025, the FDA approved it for the treatment of Barth syndrome — a rare genetic disorder associated with a defect in the mitochondrial phospholipid cardiolipin [4]. This makes SS-31 the only peptide approved by the FDA specifically for a mitochondrial disease.

In addition to Barth syndrome, SS-31 is studied in clinical programs for heart failure, age-related macular degeneration, primary mitochondrial myopathy, and age-related decline in skeletal muscle function.

For research use only. Not a medicinal product. Not intended for use in humans or animals.

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2. Why SS-31 attracts researchers' attention

SS-31 is unique on several parameters at once:

• A single target — cardiolipin. This is a phospholipid embedded exclusively in the inner mitochondrial membrane. Cardiolipin is critically important for the operation of the respiratory chain — the system that produces ATP (cellular energy). When cardiolipin is damaged, mitochondria lose efficiency. SS-31 stabilizes cardiolipin directly [1][2].

• It penetrates into mitochondria. Most molecules cannot cross the two mitochondrial membranes. SS-31 can: it concentrates in mitochondria 1,000–5,000 times higher than in the cytoplasm [1]. This is not a "systemic antioxidant" — it is a "surgical instrument" that works precisely where the energy decline begins.

• FDA approved. For Barth syndrome (2025) — the first approval of a peptide for a mitochondrial disease [4]. This confirms both the mechanism and the safety.

• A broad clinical program. Phase 2/3 in heart failure, macular degeneration, and skeletal myopathy — all of these are different manifestations of one process: mitochondrial dysfunction [3].

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3. Peptide structure

Parameter	Value
Amino acid sequence	D-Arg — Dmt — Lys — Phe-NH₂
Number of amino acids	4
Molecular weight	~640 Da
CAS number	736992-21-5
Dmt	2',6'-dimethyltyrosine (modified amino acid)
Type	Synthetic cell-penetrating tetrapeptide
Family	Szeto-Schiller (SS) peptides
Target	Cardiolipin of the inner mitochondrial membrane

Two unusual structural features make SS-31 possible:

D-arginine (instead of ordinary L-arginine) — provides resistance to enzymatic breakdown. Peptidases "do not recognize" the D-form and cannot cleave the molecule.

Dimethyltyrosine (Dmt) — a modified aromatic amino acid. It is precisely the alternation of aromatic (Dmt, Phe) and basic (D-Arg, Lys) residues that creates a structure with high affinity for cardiolipin.

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4. Cardiolipin — the key to understanding SS-31

To understand why SS-31 works, one needs to understand its target.

Cardiolipin is a unique phospholipid. It is located in only one place: in the inner mitochondrial membrane. Nowhere else in the cell does it exist. Cardiolipin performs a critical function — it "holds in place" the protein complexes of the respiratory chain (Complexes I, III, IV, and ATP synthase). Without cardiolipin, these complexes fall apart, the electron transport chain breaks, and ATP production drops.

What happens with age:

• Cardiolipin becomes oxidized (damaged by free radicals)
• The cristae (folds of the inner membrane) lose their structure
• The complexes of the respiratory chain become destabilized
• ATP production declines, electron leakage increases
• More free radicals → more damage to cardiolipin → a vicious circle

SS-31 binds directly to cardiolipin and stabilizes its structure [1][2]. In experiments, this led to restoration of cristae architecture, stabilization of the respiratory complexes, and a reduction in electron leakage. In essence, SS-31 breaks the vicious circle of "damage → dysfunction → even more damage."

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5. How SS-31 enters mitochondria

Mitochondria are surrounded by two membranes. Most molecules cannot cross both. SS-31 can, and does so without carriers or transporters.

The mechanism is electrostatic: the inner mitochondrial membrane has a strong negative membrane potential (about −180 mV). The positively charged amino acids of SS-31 (D-Arg and Lys) are attracted to this potential like a magnet. The result is that the peptide accumulates in mitochondria thousands of times faster than in the cytoplasm [1].

This property — "mitochondria-targeted delivery" — is what distinguishes SS-31 from ordinary antioxidants. Vitamin C or CoQ10 are distributed throughout the cell. SS-31 goes purposefully to where the problem is.

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6. Clinical studies

SS-31 has one of the broadest clinical programs among mitochondria-targeted molecules:

Barth syndrome (FDA approved, 2025)

A rare genetic disorder caused by a mutation in the TAFAZZIN gene, which encodes a cardiolipin-remodeling enzyme. In a Phase 2/3 study, 48-week administration of elamipretide led to a significant improvement in 6-minute walk test scores and in disease symptoms [4][5].

Heart failure

In Phase 2 studies in patients with heart failure, an improvement in peak VO₂ (maximal oxygen uptake) of 10–15% after 4 weeks of intravenous administration has been described [3].

Age-related macular degeneration (AMD)

Elamipretide is being studied in dry AMD — a condition in which the retinal pigment epithelium cells lose mitochondrial function.

Skeletal muscle and aging

In preclinical studies, Szeto and Liu (2018) described that cardiolipin-targeted peptides restore mitochondrial function and stimulate tissue regeneration in models of aging [6].

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7. SS-31 and aging

The mitochondrial theory of aging is one of the most developed in gerontology. The essence: with age, mitochondria accumulate damage, produce less ATP and more free radicals. This leads to a cascade of consequences — from a decline in muscle strength to neurodegeneration.

SS-31 is of interest in this context because it acts not on the symptoms (as antioxidants do) but on the root of the problem — damaged cardiolipin. The work of Szeto and Liu (2018) described:

• Restoration of cristae structure
• Normalization of respiratory chain function
• A reduction in the level of reactive oxygen species
• Stimulation of mitochondrial biogenesis

The authors use the phrase "rejuvenate mitochondrial function" — restoration, not merely slowing [6]. This makes SS-31 one of the most studied peptides in the field of fundamental aging research.

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8. SS-31 and MOTS-C — two approaches to mitochondria

In the LONGIVIYA catalog, two peptides target mitochondria, but through different mechanisms:

Parameter	SS-31	MOTS-C
Target	Cardiolipin (inner membrane)	AMPK (energy sensor)
Mechanism	Membrane stabilization → restoration of the respiratory chain	AMPK activation → enhancement of energy metabolism
Origin	Synthetic (Szeto-Schiller)	Endogenous (encoded in mtDNA)
Approvals	FDA (Barth, 2025)	None
Analogy	"Repairing the power plant"	"Switching on turbo mode"
Context	Restoration of damaged mitochondria	Optimization of working mitochondria

Both are included in Box 06 "Strength and Energy" — for research protocols that combine structural restoration of mitochondria (SS-31) and metabolic activation (MOTS-C).

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Sources

1. Szeto H.H. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br. J. Pharmacol., 171(8): 2029–2050, 2014. PubMed

2. Birk A.V. et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J. Am. Soc. Nephrol., 24(8): 1250–1261, 2013. PubMed

3. Szeto H.H., Birk A.V. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clin. Pharmacol. Ther., 96(6): 672–683, 2014. PubMed

4. 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. Genet. Med., 23: 471–478, 2021. PubMed

5. Hornby B. et al. Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome. Orphanet J. Rare Dis., 17: 336, 2022.

6. Szeto H.H., Liu S. Cardiolipin-targeted peptides rejuvenate mitochondrial function, remodel mitochondria, and promote tissue regeneration during aging. Arch. Biochem. Biophys., 660: 137–148, 2018. PubMed

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This material was prepared by the LONGIVIYA editorial team on the basis of published scientific research. The information is purely educational in nature and does not constitute a medical recommendation.

For research use only. Not a medicinal product. Not intended for use in humans or animals. Independent verification of every batch: Janoshik Analytical (Czech Republic).