FOXO4-DRI | Research Use Only

What it is

FOXO4-DRI is a synthetic D-retro-inverso peptide designed to interfere with the interaction between FOXO4 and p53. In the literature, it is described as a cell-permeable senolytic research peptide studied for its ability to selectively induce apoptosis in certain senescent cells, which is why it appears in aging, senescence, and tissue-repair research. Sources: MedChemExpress FOXO4-DRI, Huang et al. 2021, Bourgeois et al. 2025.

Origins and scientific context

FOXO4-DRI emerged from research into cellular senescence and the role of FOXO4-p53 signaling in maintaining the viability of senescent cells. The peptide was engineered in a D-retro-inverso format to improve stability while preserving target interaction, and later studies continued to investigate it as a tool for studying senescent-cell clearance in aging-related tissues. More recent mechanistic work still discusses FOXO4-DRI in the context of disrupting p53-related signaling in senescent cells rather than as an approved therapeutic agent. Sources: Bourgeois et al. 2025, Hu et al. 2026, Huang et al. 2021.

Molecular profile

Available chemical listings describe FOXO4-DRI as a defined synthetic peptide rather than a peptide mixture. One recent product sheet lists molecular formula C228H388N86O64, though public database coverage is less standardized than for more established compounds, so laboratory references may vary by salt form, counterion, or vendor-specific presentation. Sources: FOX04-DRI doctor sheet PDF, NovoPro FOXO4-DRI peptide.

Scientific overview

FOXO4-DRI is studied because senescent cells rely on survival pathways that differ from non-senescent cells, and disrupting the FOXO4-p53 interaction may push those cells toward apoptosis. Published work has examined FOXO4-DRI in chondrocyte senescence, endothelial senescence, and other aging-related models. Recent studies continue to describe selective effects on senescent-cell populations and downstream p53/BCL-2/Caspase-3 signaling, although the evidence remains preclinical and mechanistic rather than regulatory or therapeutic. Sources: Huang et al. 2021, Hu et al. 2026, MedChemExpress FOXO4-DRI.

What researchers study with FOXO4-DRI
Common research focus areas include
• Cellular senescence and senolytic mechanisms
• FOXO4-p53 interaction biology
• Aging-related endothelial and cartilage models
• Apoptosis signaling in senescent cells
• Tissue regeneration and age-related dysfunction research

Sources: Huang et al. 2021, Hu et al. 2026, Aging-US testosterone study.

Regulatory and compliance notice

Research Use Only. Not for human or veterinary use. FOXO4-DRI is discussed in preclinical and mechanistic research, but that does not mean it is FDA-approved for therapeutic use. Public research-product listings consistently present it as a laboratory-use peptide, and more broadly, FDA warning-letter activity in the research-peptide space makes clear that “research use only” labeling does not override intended-use concerns when products are marketed for human use. Sources: NovoPro FOXO4-DRI, FDA USApeptide.com warning letter, FDA Summit Research Peptides warning letter.

Citations and references

Huang Y, et al. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Preclinical paper examining selective removal of senescent chondrocytes.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8116695/

Hu Z, et al. FOXO4-DRI regulates endothelial cell senescence via the p53/BCL-2/Caspase-3 signaling pathway.Recent mechanistic paper describing apoptosis signaling in senescent endothelial cells.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12852416/

Bourgeois B, et al. The disordered p53 transactivation domain is the target of FOXO4 and FOXO4-DRI.Mechanistic paper on the p53 interaction basis underlying FOXO4-DRI research.
https://pubmed.ncbi.nlm.nih.gov/40593617/

MedChemExpress. FOXO4-DRI | FOXO4/p53 Interaction Blocker. Research product page summarizing its senolytic mechanism and laboratory use context.
https://www.medchemexpress.com/foxo4-dri.html

Aging-US. FOXO4-DRI alleviates age-related testosterone secretion insufficiency… Preclinical aging-related study involving FOXO4-DRI.
https://www.aging-us.com/article/102682/text

NovoPro. FOXO4 D-Retro-Inverso (DRI) peptide. Includes laboratory handling and storage context.
https://www.novoprolabs.com/p/foxo4-dri-peptide-318716.html

GenOracle. FOX04-DRI Doctor Sheet PDF. Product sheet listing molecular formula information.
https://genoracle.com/wp-content/uploads/sites/26/2025/01/FOX04-DRI-Doctor-Sheet.pdf

FDA. USApeptide.com Warning Letter. Example of FDA enforcement regarding research-peptide marketing and intended use.
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/usapeptidecom-696885-02262025

FDA. Summit Research Peptides Warning Letter. Additional FDA enforcement context for research compounds marketed for human use.
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/summit-research-peptides-695607-12102024