Comparison
Elamipretide vs. FOXO4-DRI
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Research other
CAS no.
736992-21-5
2074706-72-8
Molecular weight
639.8 g/mol
3735 g/mol
Half-life
no data
0.5 h
Sequence
D-Arg-Dmt-Lys-Phe-NH2D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Mechanism of action
Elamipretide
Elamipretide is a cell-permeable tetrapeptide with alternating aromatic and basic residues that selectively concentrates on cardiolipin — a phospholipid found almost exclusively in the inner mitochondrial membrane that is important for cristae curvature and the organisation of the respiratory-chain complexes. By binding cardiolipin, elamipretide is proposed to stabilise cristae architecture, support electron transport and ATP production, and reduce the formation of reactive oxygen species. These mechanistic models derive largely from cell and animal models and biophysical work; the extent to which they explain clinical efficacy in humans is, given the mixed trial results, a matter of ongoing research.
FOXO4-DRI
FOXO4-DRI is the D-retro-inverso variant of a peptide fragment of the FOXO4 transcription factor. In senescent cells, FOXO4 is bound to p53, which suppresses p53-mediated apoptosis — the cells survive in a secreting 'zombie-like' state (senescence-associated secretory phenotype, SASP). The DRI peptide disrupts this FOXO4-p53 binding, freeing p53, and the senescent cell initiates apoptosis. Healthy cells are largely unaffected because p53 is not held back by FOXO4 in them. This selectivity was the central finding of the original 2017 publication.
Evidence base
Highest evidence
Human RCT
Animal model
Studies
4
3
of which in humans
4
0
Effects recorded
4
3
Open conflicts
1
1
Documented adverse events
1
1
Legal status
Full entries
Frequently asked questions
- What is the difference between Elamipretide and FOXO4-DRI?
- Elamipretide is classified as "Research other", while FOXO4-DRI is classified as "Research other". Elamipretide: Elamipretide (SS-31, MTP-131, formerly Bendavia) is a synthetic, mitochondria-targeting tetrapeptide (sequence D-Arg-Dmt-Lys-Phe-NH2) that binds cardiolipin on the inner mitochondrial membrane and is proposed to stabilise cristae structure and support mitochondrial bioenergetics. It was investigated clinically by Stealth BioTherapeutics across several indications, including primary mitochondrial myopathy, Barth syndrome, heart failure, and dry age-related macular degeneration (geographic atrophy). The trial record is mixed, with several pivotal studies missing their primary endpoints. In September 2025 elamipretide (brand name Forzinity) received accelerated FDA approval in the United States solely for the ultra-rare Barth syndrome; for all other investigated indications it remains investigational and it is not approved as a medicine outside the United States. FOXO4-DRI: Synthetic peptide with D-Retro-Inverso structure (all amino acids as D-form, sequence reversed), developed in 2017 as an experimental senolytic candidate. Goal: selective apoptosis of senescent cells via disruption of the FOXO4-p53 interaction. So far evaluated exclusively preclinically. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Elamipretide or FOXO4-DRI?
- The highest available evidence level is "Human RCT" for Elamipretide and "Animal model" for FOXO4-DRI. A higher evidence level means more robust data, but says nothing about suitability for an individual. The full body of evidence is on each peptide's own page.
- What is the legal status of Elamipretide and FOXO4-DRI in Germany and the United States?
- Germany: Elamipretide — Unapproved, FOXO4-DRI — Research only. United States: Elamipretide — Prescription, FOXO4-DRI — Research only. These are factual summaries with source and review date on the individual pages.