FOXO4-DRI: Scientific Profile
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D-retro-inverso senolytic peptide (FOXO4-DRI, also called Proxofim) that antagonizes the FOXO4-p53 interaction, restoring the nuclear exclusion of p53 and inducing selective apoptosis in senescent cells without affecting healthy cells. For in vitro and preclinical research.
FOXO4-DRI, also called Proxofim (CAS 2460055-10-9; formula C228H388N86O64; ~5358 Da; 46 amino acids), is a cell-penetrating D-retro-inverso senolytic peptide. It competitively antagonizes the protein-protein interaction between FOXO4 and the tumor suppressor protein p53; by displacing p53 it restores its nuclear exclusion in senescent cells, triggering selective intrinsic (mitochondrial) apoptosis directed at cells with the senescence-associated secretory phenotype (SASP), without compromising the viability of healthy cells. Its D-retro-inverso architecture improves proteolytic stability and prolongs the half-life relative to natural L-isomers. In in vitro and preclinical research it is used to study the selective clearance of senescent cells and the modulation of senescence. Laboratory reconstitution: dissolve the lyophilizate with sterile bacteriostatic water added down the wall of the vial, swirling without shaking. Storage: keep the lyophilizate at 2-8 °C protected from light; after reconstitution keep refrigerated. Product for research (RUO).
Mechanism of action
It acts through the competitive antagonism of the FOXO4-p53 interaction. By releasing p53 from its sequestration by FOXO4 in senescent cells, it causes the exclusion of p53 from the nucleus and its translocation to the mitochondria, where it triggers intrinsic apoptosis (via BAX/caspase-3) in a transcription-independent manner, selectively eliminating those senescent cells from the tissue microenvironment.
Mechanism summary
Competitive antagonist of the FOXO4-p53 interaction: it re-establishes the nuclear exclusion of p53 in senescent cells and triggers selective intrinsic (mitochondrial) apoptosis, achieving the clearance of senescent cells (SASP) without affecting healthy cells.
Clinical Studies (6)
- The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI (Bourgeois B et al. · Nature communications · 2025) PMID 40593617.
- FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice (Liu Y et al. · Naunyn-Schmiedeberg's archives of pharmacology · 2023) PMID 37074394.
- Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes (Huang Y et al. · Frontiers in bioengineering and biotechnology · 2021) PMID 33996787.
- Regulation of cellular senescence via the FOXO4-p53 axis (Bourgeois, et al. · FEBS Letters · 2018) PMID 29683489.
- FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation (Kong YX, et al. · Communications Biology · 2025) PMID 39994346.
- FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells (Li Y, et al. · Experimental Gerontology · 2024) PMID 39025385.
Warnings
FOXO4-DRI is a compound exclusively for research use (RUO); the following warnings and handling considerations apply to its use in the laboratory:
- Exclusive use for laboratory research
- Requires strict aseptic techniques for its reconstitution
- Handle with caution to avoid mechanical degradation of the peptide chain
- Presence of active neoplastic processes in study models
- Known hypersensitivity to synthetic protein sequences
- Gestation or lactation in animal models
Technical data
- CAS
- 2460055-10-9
- Molecular formula
- C228H388N86O64
- Molecular weight
- 5358.15 Da
- Compound type
- peptide
- Storage
- -20 °C liofilizado; 2-8 °C reconstituido
- Shelf life (lyophilized)
- 24 months
- Shelf life (reconstituted)
- 14-21 days refrigerated
- Light-sensitive
- No
Available for research
FOXO4-DRI is available as a research reagent (RUO) with HPLC-verified purity and COA per batch:
Frequently asked questions about FOXO4-DRI
What is FOXO4-DRI?
D-retro-inverso senolytic peptide (FOXO4-DRI, also called Proxofim) that antagonizes the FOXO4-p53 interaction, restoring the nuclear exclusion of p53 and inducing selective apoptosis in senescent cells without affecting healthy cells. For in vitro and preclinical research.
What is the mechanism of action of FOXO4-DRI?
Competitive antagonist of the FOXO4-p53 interaction: it re-establishes the nuclear exclusion of p53 in senescent cells and triggers selective intrinsic (mitochondrial) apoptosis, achieving the clearance of senescent cells (SASP) without affecting healthy cells.
What is FOXO4-DRI researched for?
In preclinical research, FOXO4-DRI is studied mainly in: Research on the elimination of senescent cells (senolytic); Modulation of tissue regeneration in aging models; Study of the restoration of hepatic mitochondrial function. Material exclusively for scientific research.
What are the chemical properties of FOXO4-DRI?
Molecular formula C228H388N86O64; molecular weight 5358.15 Da; CAS number 2460055-10-9.
How is FOXO4-DRI stored?
Condiciones de conservación: -20 °C liofilizado; 2-8 °C reconstituido; estabilidad liofilizado: 24 meses; una vez reconstituido: 14-21 días refrigerado.
What routes of administration are studied for FOXO4-DRI?
In research models the following are described: Subcutaneous, Intraperitoneal. Use is exclusively for scientific research.