FOXO4-DRI
FOXO4-D-Retro-Inverso
Popular for:Senolytic, eliminates senescent cells, anti-aging
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Registered Trials
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Trial Publications
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PubMed References
Animal
Evidence Level
Overview
FOXO4-DRI is a D-retro-inverso peptide designed to selectively eliminate senescent cells (often called 'zombie cells') by disrupting the FOXO4-p53 interaction that keeps damaged cells alive. The short version: people usually care about it for senolytic, eliminates senescent cells, anti-aging, but the strength of the evidence depends heavily on indication and study type.
FOXO4-DRI is a D-retro-inverso peptide designed to selectively eliminate senescent cells (often called 'zombie cells') by disrupting the FOXO4-p53 interaction that keeps damaged cells alive. It was developed based on a landmark 2017 study published in Cell by Peter de Keizer's lab at Erasmus University Medical Center.
Senescent cells accumulate with age and secrete inflammatory factors (the SASP — senescence-associated secretory phenotype) that damage surrounding healthy tissue. FOXO4-DRI represents one of the most targeted senolytic approaches, designed to trigger apoptosis specifically in senescent cells while leaving healthy cells unaffected.
Research Snapshot
What the evidence says
AnimalFOXO4-DRI currently shows 0 registered trials from ClinicalTrials.gov, 0 PubMed trial publications (0 RCT-tagged), and 17 PubMed references matching the stored source query. Treat PubMed references as literature surface area, not a count of clinical trials.
Known vs uncertain
Known signals
- 0 registered trials are tracked from ClinicalTrials.gov intervention records.
- 0 PubMed clinical-trial publications are indexed.
- 0 PubMed randomized controlled trial publications are indexed.
- 17 PubMed references are tracked separately from trial counts and can include animal, in-vitro, review, mechanism, or clinical records.
Open questions
- Evidence strength may vary by indication, route, formulation, and population.
- Public anecdotes can highlight interest or concern but do not establish clinical efficacy.
- Regulatory status and compounding access can change independently from the research literature.
Mechanism of Action
In senescent cells, FOXO4 binds to p53, sequestering it and preventing p53 from triggering apoptosis.
Key Research Benefits
Clinical Evidence Summary
Research Pipeline
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Registered Trials
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Trial Publications
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RCT Publications
17
PubMed References
Registered trials are ClinicalTrials.gov intervention records. Trial publications are PubMed records tagged as clinical trials or randomized controlled trials. PubMed references are broader source-query matches and can include animal studies, in-vitro work, reviews, mechanism papers, and trial publications.
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Registered trials
0
Trial publications
0
RCT publications
17
PubMed references
4
Reviews
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Meta-analyses
Registered trials source
Jun 1, 2026
FOXO4-DRI
Uses the exact compound name as a ClinicalTrials.gov intervention query.
View sourceNot FDA-approved. Pre-clinical research compound. Based on de Keizer et al., Cell 2017. No human clinical trials completed. One of the most expensive research peptides due to synthesis complexity.
Key PubMed References
Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.
Alameen AAM, Al-Kuraishy HM, Fawzy MN, et al. · Naunyn-Schmiedeberg's archives of pharmacology · 2026
PMID: 42024235The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.
Bourgeois B, Spreitzer E, Platero-Rochart D, et al. · Nature communications · 2025
PMID: 40593617FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.
Kong YX, Li ZS, Liu YB, et al. · Communications biology · 2025
PMID: 39994346FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway.
Hu Z, Li F, Hu C, et al. · Frontiers in bioengineering and biotechnology · 2025
PMID: 41625068Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia.
Jing X, Jia S, Teng M, et al. · American journal of respiratory cell and molecular biology · 2024
PMID: 37874230Anecdotes & Sentiment
This section summarizes what people are talking about in public sources. It can be useful for spotting questions, hype cycles, and recurring concerns, but it is separate from the evidence sections above.
No curated public-discussion themes are live for FOXO4-DRI yet.
Side Effects & Safety
- Limited human safety data - Potential for off-target effects not fully characterized - Research primarily in animal models - High cost due to complex D-retro-inverso synthesis
Known Interactions
No curated interaction entry is live for FOXO4-DRI yet.
Until the interaction table is fully populated, use the interaction checker and related peptides below to explore adjacent compounds and likely research pairings.
Comparison Pages
Comparison pages
AllNo comparison page is linked yet.
Frequently Asked Questions
Research Disclaimer
This page is for research and educational purposes only. The information presented is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Regulatory status can vary by compound, formulation, indication, and jurisdiction. Check official labeling, registry records, and qualified professional guidance before making any health-related decision. The studies referenced are linked to their original PubMed sources for verification.