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Research Comparison

FOXO4-DRI vs SS-31

FOXO4-DRI and SS-31 are studied in overlapping research areas, which is why they are frequently compared. This is a neutral side-by-side reference drawn from published preclinical literature and laboratory handling data.

Shared research areas:Cellular Longevity
Class46-residue all-D retro-inverso peptideMitochondria-targeting aromatic-cationic tetrapeptide (cardiolipin-binding)
Molecular weight5358.2 g/mol639.81 g/mol
CAS number2460055-10-9Not assigned / not specified
Purity spec≥99%≥99%
Research areasCellular LongevityCellular Longevity, Metabolic
Primary diluentSterile water (USP grade)Bacteriostatic water (0.9% benzyl alcohol)
Working windowCommonly worked with for 2-3 weeks at 2-8 °C in bacteriostatic water.Commonly worked with for 3-4 weeks at 2-8 °C.
Lead degradation routeDeamidation at the Asn-Gly motif in the sequence — the fastest-deamidating dipeptide in peptide chemistry.Adsorptive loss to plasticware from the cationic charge — the main practical concern.
Freeze–thawAliquot on first reconstitution and freeze aliquots once; avoid repeated freeze–thaw cycles, which concentrate the peptide and salts at the ice interface.Tolerant; the unnatural residues resist degradation. Aliquot as standard practice.
Light sensitivityContains a tryptophan residue, which is susceptible to photo-oxidation — store in the dark.No specific light requirement beyond normal practice.

How they actually differ

Comparing the two: FOXO4-DRI is 46-residue all-d retro-inverso peptide, while SS-31 is mitochondria-targeting aromatic-cationic tetrapeptide (cardiolipin-binding) — different molecular classes with different handling consequences; they call for different primary diluents (sterile water (usp grade) versus bacteriostatic water (0.9% benzyl alcohol)); their leading degradation routes differ (deamidation at the asn-gly motif in the sequence for FOXO4-DRI, adsorptive loss to plasticware from the cationic charge for SS-31), so the storage precautions that matter are not the same; their practical working windows differ once reconstituted. The sections below set out each in full.

FOXO4-DRI — origin

FOXO4-DRI was designed in the laboratory of Peter de Keizer (Erasmus University Medical Center) and published in Cell in 2017 (Baar et al.). It mimics the region of the transcription factor FOXO4 that binds p53, but is built from D-amino acids in reversed order — a retro-inverso design that keeps the side-chain layout while making the backbone unrecognisable to proteases. A cationic, arginine-rich tail derived from the HIV-TAT cell-penetrating sequence carries it into cells.

SS-31 — origin

SS-31 (Elamipretide) is a Szeto-Schiller aromatic-cationic tetrapeptide (D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2) that concentrates in the inner mitochondrial membrane and binds cardiolipin, the lipid unique to that membrane. Its structure is the reason it is studied specifically at the mitochondrion rather than as a general antioxidant.

FOXO4-DRI research themes

FOXO4–p53 interaction in senescent cells

The founding study showed that senescent cells rely on FOXO4 holding p53 in the nucleus. Interfering with that interaction caused p53 nuclear exclusion and intrinsic apoptosis selectively in senescent cells in culture (Baar et al., Cell 2017).

Chemotoxicity and ageing mouse models

The same study examined doxorubicin-induced senescence, fast-ageing XpdTTD/TTD mice and naturally aged mice, reporting changes in fur density, fitness and renal markers.

Senescent Leydig cells

Studied in hydrogen-peroxide-induced senescent TM3 Leydig cells and aged mice for effects on the testicular microenvironment (Zhang et al., Aging 2020).

Expanded human chondrocytes

At 25 µM in vitro it removed a large share of late-passage (senescent-enriched) human chondrocytes while sparing early-passage cells, without improving cartilage-forming capacity (Huang et al., Front Bioeng Biotechnol 2021).

SS-31 research themes

Cardiolipin binding

Studied for selective association with cardiolipin in the inner mitochondrial membrane, the basis of its mitochondrial targeting.

Electron transport efficiency

Examined for effects on mitochondrial energy production in research models of mitochondrial dysfunction.

Oxidative stress

Investigated around reactive-oxygen-species handling at the mitochondrion.

FOXO4-DRI handling

  • Let the vial reach room temperature before opening.
  • Add diluent gently down the vial wall and swirl; do not vortex.
  • Use low-bind polypropylene rather than glass for dilutions — the cationic tail adsorbs to glass.
  • Protect solutions from light.

SS-31 handling

  • Reach room temperature before opening.
  • Use low-bind labware and buffers at low working concentrations to limit adsorption of the cationic peptide.
  • Aliquot and refrigerate.

Both third-party tested

Every Popular Peptides batch of FOXO4-DRI and SS-31 is independently tested by HPLC and LC-MS with a published Certificate of Analysis. Enter a lot number to pull the COA for a specific vial.

Verify a batchPublished COAsHow we test

FOXO4-DRI reference

Full FOXO4-DRI reference FOXO4-DRI storage FOXO4-DRI reconstitution FOXO4-DRI calculatorFOXO4-DRI product details

SS-31 reference

Full SS-31 reference SS-31 storage SS-31 reconstitution SS-31 calculatorSS-31 product details

Related comparisons

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FOXO4-DRI and SS-31 are supplied strictly as research chemicals for in-vitro laboratory and research use only. They are not intended for human or animal consumption, diagnostic, or therapeutic use. This comparison summarizes published preclinical literature and laboratory handling data; it is not medical advice, not a claim of efficacy, and not usage guidance.