FOXO4-DRI Explained
Imagine your body as a city where most buildings naturally demolish themselves when they get too old or damaged. But some buildings—senescent cells—have found a way to cheat death. They've essentially locked up the demolition permit (a protein called p53) in a vault using a key (FOXO4), so the building stays standing even though it should be torn down. When these zombie buildings accumulate, your city ages faster and functions worse.
FOXO4-DRI is like a master lockpick designed specifically for that vault. This synthetic peptide sneaks into senescent cells and interrupts the conversation between FOXO4 and p53, forcing the vault open. Once p53 is released, it can finally do its job—triggering these aged cells to self-destruct through a natural process called apoptosis. Healthy, young cells don't use this survival trick, so they're left alone.
The clever part is how it's built. FOXO4-DRI uses a special mirror-image structure that makes it tough enough to survive your body's natural defenses long enough to reach the nucleus where it needs to work. When researchers tested this in aging mice, they saw dramatic improvements in fitness, fur density, and kidney function—which is why it's generated so much excitement in longevity research. Essentially, you're selectively removing the cells making your body old, without harming the ones keeping you healthy.
Dosage Information
Typical Dose
5 mg/kg (animal study doses)
Frequency
3 times per week (animal protocols)
Administration
Intraperitoneal injection (animal studies), subcutaneous in human research contexts
Half-Life
2–4 hours
estimatedNotes
No established human dosing protocol. The 2017 Cell paper used mouse models. Human self-experimentation exists in the research community but safety and efficacy data in humans is essentially absent. Approach with significant caution.
Why this matters
Senolytic peptide; induces apoptosis in senescent cells with effects beyond plasma clearance.
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Evidence Score
0.28
Compound Data
Molecular Formula
C228H388N86O64
Molecular Weight
5358.00 g/mol
IUPAC Name
(4R)-5-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-5-amino-1-[[(2R)-4-amino-1-[[2-[[(2R)-1-[[(2R)-1-[[(2R)-4-amino-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[2-[[2-[[(2R)-6-amino-1-[[(2R)-1-[(2R)-2-[(2R)-2-[(2R)-2-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-5-amino-1-[[(2R)-1-[[(2R)-1-[[(2R)-6-amino-1-[[(2R)-6-amino-1-[[(2R)-5-carbamimidamido-1-(carboxymethylamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1,4-dioxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2R)-2-[[(2R,3R)-2-[[(2R)-2-[[(2R)-5-amino-2-[[(2R)-2-[[(2R,3R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-1-[(2R)-2-[[(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R,3S)-2-[[(2R)-2-amino-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoic acid
PubChem CID
167312269Potential Side Effects
FOXO4-DRI discussions
Quick Facts
- Administration
- Intraperitoneal injection (animal studies), subcutaneous in human research contexts
- Typical Dose
- 5 mg/kg (animal study doses)
- Frequency
- 3 times per week (animal protocols)
- References
- 0 curated + 42 from PubMed
- Evidence Score
- 0.3 / 100
Frequently Asked Questions about FOXO4-DRI
What is FOXO4-DRI?
FOXO4-DRI is a synthetic D-amino acid retro-inverso peptide designed to selectively eliminate senescent cells by interfering with the interaction between the FOXO4 transcription factor and p53 that senescent cells depend on for survival. It represents one of the most targeted senolytic approaches developed to date acting specifically on the aberrant survival pathway of senescent cells without affecting normal healthy cells. Research published in Cell in 2017 demonstrated dramatic effects including restoration of fur density fitness and kidney function in aged mice generating significant excitement in the longevity research community.
How does FOXO4-DRI work?
Senescent cells avoid apoptosis through an abnormal survival pathway in which FOXO4 binds to p53 in the nucleus sequestering it and preventing p53-mediated apoptosis induction. FOXO4-DRI is designed to competitively disrupt this FOXO4-p53 interaction. By blocking FOXO4 from sequestering p53 the peptide liberates p53 to execute its normal apoptotic function in senescent cells restoring their ability to undergo programmed cell death. Normal healthy cells do not depend on the FOXO4-p53 interaction for survival making FOXO4-DRI selectively toxic to senescent cells. The D-amino acid retro-inverso design makes the peptide resistant to protease degradation improving its pharmacokinetic stability compared to L-amino acid versions while retaining the ability to penetrate cells and reach the nuclear FOXO4-p53 complex.
What is the recommended dosage for FOXO4-DRI?
The typical dose is 5 mg/kg (animal study doses). 3 times per week (animal protocols). Administration: Intraperitoneal injection (animal studies), subcutaneous in human research contexts. No established human dosing protocol. The 2017 Cell paper used mouse models. Human self-experimentation exists in the research community but safety and efficacy data in humans is essentially absent. Approach with significant caution.
What are the side effects of FOXO4-DRI?
Very limited human safety data. Theoretical risk of eliminating beneficial senescent cells involved in wound healing. Injection site reactions. Unknown long-term effects
Questions reflect common community inquiries. This is not medical advice.