FOXO4-DRI (Proxofim)
Also known as: FOXO4-DRI, FOX04-DRI, Proxofim
FOXO4-DRI is a synthetic senolytic peptide studied for selectively clearing senescent cells to counter age-related tissue decline.
Last updated
Mechanism of Action
FOXO4-DRI is a retro-inverso (D-amino-acid) peptide designed to interfere with the interaction between the FOXO4 transcription factor and p53 within senescent cells. In senescent cells FOXO4 sequesters p53 in the nucleus to keep these cells alive despite damage; by competitively disrupting this FOXO4-p53 binding, the peptide releases p53, which relocates to mitochondria and triggers apoptosis. Because senescent cells are uniquely dependent on this interaction for survival, the peptide acts as a senolytic, selectively eliminating them while sparing healthy cells.
- Half-life
- Short peptide half-life; D-amino-acid design improves protease resistance
- Administration Routes
- subcutaneous, intravenous
- Research Status
- Preclinical
Reported Benefits
- Selectively induces apoptosis in senescent cells
- Studied for reducing senescence-associated inflammation
- May restore fitness, fur density, and renal function in aged mouse models
- Investigated for counteracting age-related tissue decline
- Potential to reduce chemotherapy-induced senescence damage
Potential Side Effects
- Limited human safety data
- Possible injection-site reaction
- Theoretical off-target effects on p53 signaling
- Unknown long-term effects in humans
Common Dosing
Mouse studies used intraperitoneal doses around several mg/kg given on intermittent schedules; no validated human dosing exists. For research use only; not personal medical advice.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Known hypersensitivity to the peptide
- Pregnancy or breastfeeding
- Caution with active malignancy given p53 pathway modulation
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Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
2017
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The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI
2025
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Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes
2021
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FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
2020