SS-31 (Elamipretide)
SS-31 (elamipretide) is a mitochondria-targeting tetrapeptide that binds cardiolipin in the inner mitochondrial membrane and, in September 2025, became the first such peptide to receive FDA accelerated approval (as FORZINITY) for the ultra-rare Barth syndrome while remaining investigational for other indications.
SS-31 — known generically as elamipretide and historically as MTP-131, Bendavia, and RX-31 — is a synthetic cell-permeable tetrapeptide developed by Stealth BioTherapeutics. Its sequence is D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2, an aromatic-cationic motif that lets the molecule cross the plasma membrane and concentrate in the inner mitochondrial membrane without depending on the membrane potential.
Mechanistically, elamipretide binds reversibly to cardiolipin, the signature phospholipid of the inner mitochondrial membrane. In preclinical work this association is reported to stabilize cristae architecture and the cardiolipin-dependent assembly of electron-transport-chain supercomplexes, with downstream effects described as improved ATP production and reduced reactive-oxygen-species output in stressed cells. These are mechanistic findings from laboratory and animal models rather than established clinical outcomes.
In September 2025 elamipretide became the first mitochondria-targeted therapeutic to gain FDA approval. The agency granted accelerated approval on 19 Sep 2025 for the brand FORZINITY (elamipretide hydrochloride, NDA 215244) to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg — an ultra-rare X-linked disorder caused by TAFAZZIN mutations that disrupt cardiolipin remodelling. The approval drew on the randomized, placebo-controlled crossover TAZPOWER trial (NCT03098797) and its open-label extension. Outside this single indication the peptide remains investigational: it has been studied for heart failure and ischemia-reperfusion injury (formerly under the name Bendavia), acute and chronic kidney disease, primary mitochondrial myopathy, and dry age-related macular degeneration, without approvals for those uses. It is not authorized by the UK MHRA or the EMA.
In the clinical program the most common adverse reactions were injection-site reactions (erythema, induration, pruritus, pain), generally mild-to-moderate; hypersensitivity reactions have been reported. The approved injectable contains benzyl alcohol as a preservative and is not approved for use in neonates. Material sold elsewhere as a "research chemical" is unregulated, with no assurance of identity, purity, sterility, or dosing, and long-term safety is not established. This entry is reference information only and is not a recommendation for use.
A cell-permeable aromatic-cationic tetrapeptide (D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2) that selectively concentrates in the inner mitochondrial membrane and binds reversibly to cardiolipin. This association is reported to stabilize mitochondrial cristae architecture and the cardiolipin-dependent assembly of electron-transport-chain supercomplexes, with downstream effects on ATP production and reduced reactive-oxygen-species output in preclinical models.
- Human evidence
- Human clinical-trial data (Phase 2/3); FDA accelerated approval for one ultra-rare indication (Barth syndrome)
- Regulatory status
- Received FDA accelerated approval on 19 Sep 2025 as FORZINITY (elamipretide HCl, Stealth BioTherapeutics, NDA 215244) for Barth syndrome in patients weighing at least 30 kg — the first approved mitochondria-targeted therapeutic. It remains investigational (not approved) for all other indications under study (e.g. heart failure, acute kidney injury, primary mitochondrial myopathy, dry AMD). Not approved by the UK MHRA or EMA; supplied elsewhere as a research chemical, not a licensed medicine.
- Studied in research and clinical trials as a mitochondria-targeted agent for primary mitochondrial diseases, including the Barth syndrome program that supported its accelerated approval.
- Investigated preclinically and clinically for cardiovascular conditions such as heart failure and ischemia-reperfusion injury (formerly branded Bendavia).
- Examined in models of acute kidney injury and chronic kidney disease for effects on mitochondrial structure and function.
- Used as a tool compound in aging and longevity research to probe cardiolipin biology, cristae stability and bioenergetic decline.
- In the controlled and open-label clinical program the most common adverse reactions were injection-site reactions (erythema, induration, pruritus, pain); per the FORZINITY prescribing information these are generally mild-to-moderate.
- Hypersensitivity reactions have been reported; the approved injectable formulation contains benzyl alcohol as a preservative and is not approved for use in neonates (benzyl alcohol has been associated with serious, sometimes fatal, reactions in low-birth-weight and preterm newborns).
- In the TAZPOWER open-label extension, 2 of 10 participants discontinued because of treatment-related injection-site reactions, indicating tolerability is not universal.
- Long-term safety and the safety of unregulated 'research chemical' material (purity, sterility, dosing) are not established; this entry is reference material only and is not a use recommendation.
- [1]PubChem Compound: Elamipretide (CID 11764719)PubChem
- [2]Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential (PMC11816484)PubMed Central
- [3]Stealth BioTherapeutics Announces FDA Accelerated Approval of FORZINITY (elamipretide HCl)Stealth BioTherapeutics (PR Newswire)
- [4]FORZINITY (elamipretide) Prescribing InformationFDA