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Last reviewed: March 2026Sources: PubMed, FDA, WADA Prohibited List

Evidence graded using the PeptideScholar A-D system

FOXO4-DRI

DLimited Data
50
Fair Credibility
1 cited studyy · Evidence level D

Retro-inverso senolytic peptide · 10 amino acids

Not FDA Approved

FOXO4-DRI is a synthetic retro-inverso peptide designed to disrupt the FOXO4-p53 interaction, selectively inducing apoptosis in senescent cells. It was the first senolytic peptide with published in vivo data, demonstrating the feasibility of targeted senescent cell clearance. Also known by the development name Proxofim.

Mechanism of Action

Mimics the FOXO4-p53 interaction domain but with D-amino acids (retro-inverso configuration) that resist proteolysis. Displaces endogenous FOXO4 from p53 in senescent cells, releasing active p53 to trigger apoptosis. Normal cells are unaffected because they do not rely on the FOXO4-p53 axis for survival.

Benefits

  • First senolytic peptide with in vivo proof-of-concept data
  • Selectively clears senescent cells without harming normal cells[1]
  • Restores tissue homeostasis in aged and chemotoxicity models[1]
  • Improves physical function (grip strength, coat condition) in aged mice[1]
Not Medical Advice — Research-Reported Information Only

This content is for informational purposes only and does not constitute medical advice.

FOXO4-DRI — Dosing in Published Research

Reported Routes: Subcutaneous injection, Intravenous
No human dosing established. Mouse studies used 5 mg/kg intraperitoneal injections. The peptide is not commercially available as a pharmaceutical product. Research use only.

The dosing information above is sourced from published research literature and clinical trials. These are not recommendations. Individual responses vary. Always consult a healthcare provider before considering any peptide-based therapy.

Side Effects

  • No human clinical data exists
  • Unknown long-term safety of senescent cell clearance
  • Theoretical risk of removing beneficial senescent cells (wound healing, embryogenesis)[1]
  • Not approved for human use

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FOXO4-DRI is not FDA-approved. Always consult a licensed healthcare provider before considering any peptide.

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Research & Evidence

AnimalCell, 2017

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.

FOXO4-DRI selectively induced apoptosis in senescent cells, restored tissue homeostasis, and improved physical function in aged and chemotherapy-treated mice

PMID: 28340339

References

  1. 1. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.. Cell, 2017. “FOXO4-DRI selectively induced apoptosis in senescent cells, restored tissue homeostasis, and improved physical function in aged and chemotherapy-treated mice” [PMID: 28340339]

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FOXO4-DRI FAQ

Medical Disclaimer

This content is for informational and educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.

Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment. Do not disregard professional medical advice based on information found on this site.

No claims of therapeutic efficacy are made for substances that are not FDA-approved for the discussed indications. Research citations reflect published findings and do not imply endorsement.

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