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FOXO4-DRI

For In-Vitro Laboratory Research Use Only • Not for Human or Veterinary Use

FOXO4-DRI Research Peptide

FOXO4-DRI is a D-retro-inverso (DRI) peptide, built from D-amino acids in reversed sequence, a design used to increase resistance to proteases. It was designed by Baar and colleagues (2017) to interfere with the interaction between the FOXO4 and p53 proteins.

In the published literature, FOXO4-DRI has been investigated in cell and animal models in the context of cellular senescence.

Specifications

  • Peptide type: D-retro-inverso peptide
  • Research target: FOXO4–p53 interaction
  • Size: 10mg

Certificate of Analysis will be published on our Verification page when available.

Made to order: please allow 14–16 days in total, including delivery.

For in-vitro laboratory research use only. Not for human or veterinary use.

£79.99 / vialFrom £67.99 / vial (15% Multi-Vial Savings)

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FOR IN-VITRO LABORATORY RESEARCH USE ONLY — NOT FOR HUMAN OR VETERINARY USE

These products are research chemicals. They are not medicines, food, or supplements. They have not been evaluated by the MHRA, FDA, or any other regulatory body. Not intended to diagnose, treat, cure, or prevent any disease. All descriptions are for reference and research documentation purposes only. By purchasing, you confirm you are aged 18+ and using these products exclusively for in vitro laboratory research.

About FOXO4-DRI

FOXO4-DRI is a synthetic D-retro-inverso (DRI) peptide: it is built from D-amino acids in reversed sequence, a design used to make peptides more resistant to breakdown by proteases. It was designed by Baar and colleagues in 2017 to interfere with the interaction between the FOXO4 and p53 proteins [1]. PubChem lists its molecular formula as C228H388N86O64, with a molecular weight of approximately 5358 g/mol.

FOXO4-DRI has not been approved as a medicine by the MHRA, the FDA or any other regulator. The product sold here is a research compound for laboratory use only. For an overview of the published literature, see our longevity peptides research summary. Related research compounds include Epitalon and SS-31.

Areas of research

FOXO4-DRI is studied mainly in the context of cellular senescence, the state in which damaged cells stop dividing but do not die. Published work includes:

  • the original design of the peptide and studies of senescent cell viability in cell and mouse models [1]
  • studies of senescent Leydig cells in cell culture and in aged mice [2]
  • studies of senescent endothelial cells and the p53 signalling pathway [3]
  • NMR structural studies of how FOXO4-DRI binds the disordered transactivation domain of p53 [4]

All of this work comes from cell and animal models, and the evidence base remains at an early, preclinical stage.

Product specifications

Form Lyophilised (freeze-dried) powder in a sealed vial
Size 10mg
Peptide type D-retro-inverso peptide
Research target FOXO4–p53 interaction
Molecular formula C228H388N86O64 (PubChem)
Molecular weight approx. 5358 g/mol (PubChem)
Purity No COA published yet. The Certificate of Analysis will be published on our verification page when available.
Availability Made to order: please allow 14–16 days in total, including delivery

Storage and handling

Storage & Handling — Corex Vitality™ research vials

  • As supplied: freeze-dried (lyophilised) powder in a sealed vial. Room-temperature transit is normal for dry peptides.
  • Longer storage: keep the vial tightly closed in a freezer at −20 °C or colder, dry and away from light. Colder is better for long archives.
  • Short-term: a laboratory fridge (2–8 °C) is fine for vials you plan to open soon.
  • Before opening: let the closed vial warm to room temperature, ideally in a desiccator, so moisture does not condense on the powder. Work quickly and reseal tightly; absorbed moisture lowers the real peptide content.
  • Dissolving: choose a solvent based on the sequence (see the compound note below) and test a small portion first. Swirl gently; brief sonication in a water bath can help. Do not heat.
  • Once in solution: make up only what you need. Split any solution you keep into single-use aliquots, freeze at −20 °C or colder and thaw each aliquot only once. Peptides keep far less well in solution than as dry powder.
  • Safety: handle in a suitable laboratory with appropriate PPE, following your institution’s safety procedures, and avoid breathing the powder. Keep out of reach of children.

Compound note: Oxidation-sensitive: long, strongly basic (Arg/Lys-rich) peptide with one tryptophan and several Asn/Gln residues. Usually dissolves in water or dilute acetic acid; protect from light and oxygen, and do not keep it in solution.

For in-vitro laboratory research use only. Not for human or veterinary use. General guidance paraphrased from Bachem: Handling and Storage Guidelines for Peptides and Peptide Solubility.

Quality and testing

No Certificate of Analysis has been published for FOXO4-DRI yet; it will appear on our verification page when issued. You can also browse every published certificate on our COA and verification page.

Research use only

For in-vitro laboratory research use only. Not for human or veterinary use. These products are research chemicals. They are not medicines, food, or supplements. They have not been evaluated by the MHRA, FDA, or any other regulatory body. Not intended to diagnose, treat, cure, or prevent any disease. All descriptions are for reference and research documentation purposes only. By purchasing, you confirm you are aged 18+ and using these products exclusively for in vitro laboratory research.

References

  1. Baar MP, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell. 2017. PubMed 28340339
  2. Zhang C, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY). 2020. PubMed 31959736
  3. Hu Z, et al. FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway. Front Bioeng Biotechnol. 2025. PubMed 41625068
  4. Bourgeois B, et al. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nat Commun. 2025. PubMed 40593617

Research you can verify.

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🎬 Scientific Explainer Video · What It Is For & How It Works

FOXO4-DRI — Laboratory Mechanism & Research Overview

⬇ Download Video (MP4) All Peptide Videos →
🔬 What Is This Peptide Researched For?
  • Studying selective disruption of the nuclear FOXO4–p53 protein–protein interaction in senescent cells
  • Investigating D-retro-inverso stereochemistry resistance against intracellular proteolytic cleavage
  • Examining Senescence-Associated Secretory Phenotype (SASP) attenuation in pre-clinical ageing models
⚙️ How Does It Work? (Mechanism of Action)
1. HIV-TAT Cell-Penetrating Entry: Crosses the plasma and nuclear membranes via its N-terminal TAT basic translocation motif.
2. Competitive FOXO4–p53 Displacement: Binds the p53 transactivation domain with high affinity, freeing p53 from FOXO4 nuclear foci.
3. Nuclear Exclusion & Intrinsic Apoptosis: Phosphorylated p53 translocates to mitochondria, triggering caspase-3/7 apoptosis in senescent cells.
📚 Peer-Reviewed Literature · PubMed Indexed

Published Research — FOXO4-DRI (D-Retro-Inverso FOXO4 Peptide)

NCBI PubMed Database ↗ Verify Batch COAs →
  1. [1] Baar MP et al. · Cell (2017)

    Foundational study designing the cell-permeable D-retro-inverso peptide FOXO4-DRI, demonstrating competitive disruption of nuclear FOXO4–p53 PML-body complexes, p53 nuclear exclusion, and selective caspase-3/7-mediated apoptosis in senescent cells.

    PMID: 28340339 ↗ DOI: 10.1016/j.cell.2017.02.031 ↗
  2. [2] Huang Y et al. · Front Bioeng Biotechnol (2021)

    In-vitro serial population-doubling culture study demonstrating that FOXO4-DRI selectively clears SA-β-gal-positive senescent chondrocytes and reduces senescence-associated secretory phenotype (SASP) marker expression.

    PMID: 33996787 ↗ DOI: 10.3389/fbioe.2021.677576 ↗
  3. [3] Kim J et al. · FEBS J (2022)

    NMR spectroscopy and isothermal titration calorimetry (ITC) study mapping the molecular binding interface between the FOXO4 forkhead-associated domain and the p53 transactivation domain.

    PMID: 34954873 ↗ DOI: 10.1111/febs.16333 ↗
  4. [4] Bourgeois B et al. · Nat Commun (2025)

    High-resolution NMR, small-angle X-ray scattering (SAXS), and biochemical study demonstrating that FOXO4-DRI directly binds the intrinsically disordered p53 transactivation domain (TAD) with higher affinity than native FOXO4.

    PMID: 40593617 ↗ DOI: 10.1038/s41467-025-60844-9 ↗

References are provided for scientific context only. All Corex Vitality™ compounds are supplied strictly for in-vitro laboratory research use (RUO).