SS-31 (Elamipretide) — clinical & mechanistic profile
SS-31 (elamipretide) is a mitochondria-targeting tetrapeptide that binds cardiolipin on the inner mitochondrial membrane. FDA-approved for Barth syndrome (FORZINITY). 2025-2026 preclinical data shows neuroprotection: upregulates mitochondrial biogenesis against Aβ in Alzheimer's models, protects dopaminergic neurons in Parkinson's, and improves retinal survival in diabetic models. AMD trials slowed progressive ellipsoid zone degradation.
Research status
clinical investigational
Sequence
D-Arg-Dmt-Lys-Phe-NH2
Molecular weight
639.76 g/mol
Molecular formula
C32H49N9O5
Studied applications
- •Cardiolipin binding: stabilizes cardiolipin content, prevents peroxidation and oxidation critical for mitochondrial structure and ETC function
- •Membrane stabilization: protects cristae structure and prevents destabilization during apoptosis
- •mPTP inhibition: inhibits mitochondrial permeability transition pore opening, accelerates ATP supply
- •Calcium stress reduction: modulates surface electrostatics of mitochondrial membranes, reducing calcium stress
- •FDA approval: approved as FORZINITY for Barth syndrome (2025)
- •Selective action: rapidly improves physiological function in aging and mitochondrial disorders, no effect on healthy mitochondria
Mechanisms of action
- •Cardiolipin interaction: binds reversibly to cardiolipin, stabilizing content and preventing peroxidation/oxidation
- •Cristae protection: maintains cristae structure and prevents destabilization during apoptosis
- •mPTP regulation: inhibits mitochondrial permeability transition pore opening, promotes electron transfer while reducing electron leakage
- •Multiple protein interactions: interacts with cardiolipin-binding proteins involved in oxidative phosphorylation and metabolic processes
- •ROS suppression: prevents cardiolipin oxidation, reduces reactive oxygen species, decreases apoptosis
- •Membrane electrostatics: modulates surface electrostatics, alters ion distribution, reduces calcium stress
- •FDA approved only for Barth syndrome—other indications still investigational
- •Clinical trials for primary mitochondrial myopathy showed mixed Phase 3 results
- •Selective for dysfunctional mitochondria—no benefit in healthy tissue
- •Subcutaneous administration required for chronic use
- •Cost and availability limitations as orphan drug
Peer-reviewed references
- SS-31 mitochondrial mechanisms in aging musclePMID: 26631564View
- Elamipretide cardiolipin interaction (PNAS 2020)PMID: 32341003View
- Phase 2 trial in primary mitochondrial myopathy (Neurology 2018)PMID: 29241563View
- Heart failure mechanisms and clinical potentialPMID: 30127997View
- PMC9192202 — SS-31 comprehensive mechanisms review
For research use only. This summary is a research-scientific overview compiled from peer-reviewed sources. It is not medical advice and is not intended for human or veterinary consumption.
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