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Research Comparison

FOXO4-DRI vs Glutathione

FOXO4-DRI and Glutathione 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 peptideEndogenous thiol tripeptide (γ-L-glutamyl-L-cysteinyl-glycine), reduced form
Molecular weight5358.2 g/mol307.3 g/mol
CAS number2460055-10-970-18-8
Purity spec≥99%≥99%
Research areasCellular LongevityCellular Longevity, Metabolic
Primary diluentSterile water (USP grade)Sterile water (USP grade)
Working windowCommonly worked with for 2-3 weeks at 2-8 °C in bacteriostatic water.Commonly worked with for about 1 week at 2-8 °C; frozen aliquots keep longer.
Lead degradation routeDeamidation at the Asn-Gly motif in the sequence — the fastest-deamidating dipeptide in peptide chemistry.Oxidation of the cysteine thiol to glutathione disulfide (GSSG, about 612.6 Da), catalysed by trace Cu²⁺/Fe³⁺ and faster at neutral-to-alkaline pH.
Freeze–thawAliquot on first reconstitution and freeze aliquots once; avoid repeated freeze–thaw cycles, which concentrate the peptide and salts at the ice interface.Tolerates a few freeze-thaw cycles, but each thaw exposes the thiol to dissolved oxygen. Aliquot once and thaw each portion only once.
Light sensitivityContains a tryptophan residue, which is susceptible to photo-oxidation — store in the dark.Not strongly light-sensitive, but oxygen-sensitive: minimise headspace and avoid metal spatulas or metal-contaminated buffers.

How they actually differ

Comparing the two: FOXO4-DRI is 46-residue all-d retro-inverso peptide, while Glutathione is endogenous thiol tripeptide (γ-l-glutamyl-l-cysteinyl-glycine), reduced form — different molecular classes with different handling consequences; their leading degradation routes differ (deamidation at the asn-gly motif in the sequence for FOXO4-DRI, oxidation of the cysteine thiol to glutathione disulfide (gssg, about 612.6 da), catalysed by trace cu²⁺/fe³⁺ and faster at neutral-to-alkaline ph. for Glutathione), 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.

Glutathione — origin

Glutathione is the tripeptide γ-glutamyl-cysteinyl-glycine. The glutamate is joined through its side-chain (γ) carboxyl rather than the usual α link, which protects it from most peptidases. It was named by Frederick Gowland Hopkins in 1921, and its role in cellular redox chemistry was mapped out through the 20th century, most influentially in Alton Meister's work on the γ-glutamyl cycle.

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).

Glutathione research themes

Cellular redox buffering (GSH/GSSG ratio)

Glutathione is the most abundant low-molecular-weight thiol in most cells, and the ratio of reduced to oxidised glutathione is widely used as a read-out of oxidative stress in cell-culture and tissue studies.

The γ-glutamyl cycle

Meister and Anderson (Annu Rev Biochem 1983) reviewed glutathione synthesis by γ-glutamylcysteine synthetase and glutathione synthetase, and its breakdown by γ-glutamyl transpeptidase — the framework most synthesis and turnover studies still use.

Detoxification by glutathione S-transferases

GSTs conjugate glutathione to electrophilic compounds, and this conjugation step is a standard model in xenobiotic-metabolism research.

The glutathione peroxidase system

Glutathione peroxidases use GSH to reduce hydrogen peroxide and lipid hydroperoxides, with glutathione reductase recycling GSSG back to GSH using NADPH — a common model for studying peroxide handling in vitro.

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.

Glutathione handling

  • Let the vial reach room temperature before opening to stop condensation getting in.
  • Use degassed diluent where possible and cap promptly after drawing.
  • Avoid metal tools and buffers with trace copper or iron; plastic or glass only.
  • Label aliquots with reconstitution date and diluent.

Both third-party tested

Every Popular Peptides batch of FOXO4-DRI and Glutathione 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

Glutathione reference

Full Glutathione reference Glutathione storage Glutathione reconstitution Glutathione calculatorGlutathione product details

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FOXO4-DRI and Glutathione 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.