FOX04-DRI
FOX04-DRI is a cell-penetrating D-retro-inverso peptide designed to selectively induce apoptosis in senescent cells by disrupting the interaction between FOXO4 and p53, which normally maintains senescent cell survival. Animal studies showed restoration of physical fitness, renal function, and fur density following treatment.
Written by WhatPeptide Editorial Team · Last updated 2026-03-17
Half-life
Estimated 2-4 hours based on D-amino acid stability
Dosage range
1-5 mg/kg (animal studies only; no established human dose)
Administration
Subcutaneous injection
Research level
Animal only
How FOX04-DRI works
Senescent cells upregulate FOXO4, which sequesters p53 in the nucleus and prevents apoptosis, allowing the accumulation of the senescent cell burden associated with aging. FOX04-DRI competitively antagonizes this interaction, freeing p53 to translocate to mitochondria and trigger apoptosis selectively in senescent cells without affecting healthy proliferating cells. Published mouse data demonstrated measurable reductions in senescent cell markers and improvement in age-related physical decline.
Also known as: FOXO4-D-Retro-Inverso, FOX04 peptide
Research relevance
Side effects & safety
Contraindications
Consult a healthcare provider before use if any of these apply to you.
Key studies
-
Baar MP et al. — Targeted apoptosis of senescent cells restores tissue homeostasis
Foundational Cell paper: FOXO4-DRI disrupts FOXO4-p53 interaction causing selective senescent cell apoptosis; restored fitness in aged mice
PubMed 2017 -
Zhang C et al. — FOXO4-DRI alleviates age-related testosterone insufficiency
Eliminates senescent Leydig cells in aged mice, improving testicular microenvironment and testosterone secretion
PubMed 2020 -
Le HH et al. — Molecular modelling of FOXO4-TP53 for improved senolytic peptides
Rationally designed ES2 peptide disrupts FOXO4-TP53 foci; senolytic in cell culture and orthotopic mouse models; reduced senescent cells in aged mouse liver
PubMed 2021
FAQ
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