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Research Comparison

Epithalon vs FOXO4-DRI

Epithalon and FOXO4-DRI 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
ClassSynthetic tetrapeptide (Ala-Glu-Asp-Gly)46-residue all-D retro-inverso peptide
Molecular weight390.35 g/mol5358.2 g/mol
CAS number307297-39-82460055-10-9
Purity spec≥98%≥99%
Research areasCellular Longevity, Circadian & SleepCellular Longevity
Primary diluentSterile or bacteriostatic waterSterile water (USP grade)
Working windowCommonly worked with for 3–4 weeks at 2–8 °C.Commonly worked with for 2-3 weeks at 2-8 °C in bacteriostatic water.
Lead degradation routeAspartate-glycine isomerisation — the Asp-Gly motif is among the most isomerisation-prone sequences in peptide chemistry, and Epithalon contains it.Deamidation at the Asn-Gly motif in the sequence — the fastest-deamidating dipeptide in peptide chemistry.
Freeze–thawHighly tolerant. A four-residue peptide has essentially no structure to disrupt, making this one of the more freeze-tolerant compounds in the catalogue.Aliquot on first reconstitution and freeze aliquots once; avoid repeated freeze–thaw cycles, which concentrate the peptide and salts at the ice interface.
Light sensitivityNo specific light requirement beyond normal practice.Contains a tryptophan residue, which is susceptible to photo-oxidation — store in the dark.

How they actually differ

Comparing the two: Epithalon is synthetic tetrapeptide (ala-glu-asp-gly), while FOXO4-DRI is 46-residue all-d retro-inverso peptide — different molecular classes with different handling consequences; they call for different primary diluents (sterile or bacteriostatic water versus sterile water (usp grade)); their leading degradation routes differ (aspartate-glycine isomerisation for Epithalon, deamidation at the asn-gly motif in the sequence for FOXO4-DRI), 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.

Epithalon — origin

Epithalon is a four-residue peptide derived by Vladimir Khavinson's group from Epithalamin, a pineal gland extract studied in the Soviet Union from the 1970s. It represents the reductionist end of the peptide field — the attempt to identify the shortest sequence retaining the activity of a complex tissue extract. At 390 Da it is the smallest compound in this catalogue by a wide margin.

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.

Epithalon research themes

Telomerase activation

The most-cited claim in the Epithalon literature, examined in cell-culture models.

Pineal and melatonin rhythm

Follows from its Epithalamin origin; studied for effects on circadian signalling in animal models.

Ageing models

A long-running Russian research programme examined lifespan endpoints in rodent models.

Peptide bioregulator concept

Epithalon is the flagship of Khavinson's "peptide bioregulator" framework, a distinct research tradition worth understanding as context.

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).

Epithalon handling

  • Do not over-engineer storage for this compound — refrigeration and a sound seal are genuinely sufficient.
  • Avoid prolonged storage of reconstituted solution, since Asp-Gly isomerisation is slow but cumulative.
  • Verify the analytical method behind any purity figure, as short polar peptides are easy to under-resolve.

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.

Both third-party tested

Every Popular Peptides batch of Epithalon and FOXO4-DRI 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

Epithalon reference

Full Epithalon reference Epithalon storage Epithalon reconstitution Epithalon calculatorEpithalon product details

FOXO4-DRI reference

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

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Epithalon and FOXO4-DRI 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.