FOXO4-DRI
A senolytic peptide that clears senescent cells in mice and cultured cells, and has never been given to a person.
A mirror-image peptide that separates FOXO4 from p53 inside senescent cells so they die, tested only in animals and cells.
Mechanism of action
Competitively inhibits the FOXO4-p53 protein-protein interaction that is specific to senescent cells. In senescent cells, this interaction sequesters p53 in the nucleus and prevents it from triggering apoptosis (part of the senescent phenotype). FOXO4-DRI disrupts this sequestration, freeing p53 to translocate to mitochondria and induce apoptosis specifically in p16-positive senescent cells — leaving non-senescent cells unaffected.
Primary uses
- Senescent cell research
- Aging biology (preclinical)
- Community anti-aging use (no human safety data)
Typical dosing
No human dosing established. Community use carries substantial unknown risk given the pro-apoptotic mechanism.
Regulatory status
Not approved anywhere and never trialled in people. No application appears in FDA's Drugs@FDA database and no clinical trial of the peptide is published or recruiting.
Status as of this entry's last review, September 30, 2026. Approvals, compounding rules and sport rules change; the regulatory tracker is checked more often.
What we checked
FOXO4-DRI is a senolytic peptide that removes senescent cells in mice and in cell cultures. It has never been given to a person; this section records what can be checked.
Identity, computed
| Sequence | Not established |
FOXO4-DRI is a D-retro-inverso peptide: a FOXO4 segment built from D-amino acids in reverse order, with a cell-entry sequence attached. The site's calculator models L-peptides only, so no formula or mass is computed here; the dataset's stated mass is not repeated.
Regulatory status, read October 5, 2026
Drugs@FDA: 0 records for “FOXO4-DRI”. EMA medicines list: 0 records for “FOXO4”. Run for semaglutide, the same queries return 6 and 5 records (and the registry search 84 trials), so a zero here is an absence, not a broken search. Not named on the WADA 2026 and 2027 Prohibited Lists. As a substance with no current approval for human therapeutic use, it falls under section S0 (non-approved substances), which is prohibited at all times; the lists were read on September 27, 2026.
What the maker or sellers claim
Claim, from research-chemical sellers and longevity forums: FOXO4-DRI clears senescent cells and reverses ageing in people. Every published study is in mice or cells.
About senescent cells and senolytics
Senescent cells stop dividing but resist death and secrete inflammatory signals. The 2017 founding study, cited in References, designed FOXO4-DRI to disrupt FOXO4's hold on p53 in those cells, and later mouse studies applied it to fibrosis, testes and skin. Our FOXO4-DRI article covers the senolytic field.
What we looked for and did not find
No human study, no registry record, no pharmacokinetic data in people and no dose from a controlled human study.
| Source | Query | Results, October 5, 2026 | What it was |
|---|---|---|---|
| PubMed | FOXO4-DRI | 19 | the senolytic peptide literature |
| ClinicalTrials.gov | FOXO4 | 0 | |
| Drugs@FDA (openFDA) | FOXO4-DRI | 0 | |
| EMA medicines list | FOXO4 | 0 |
References
- [pubmed] Baar MP, et al. "Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging." Cell, 2017;169(1):132-147.e16. PMID: 28340339.
- [pubmed] Bourgeois B, et al. "The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI." Nat Commun, 2025;16(1):5672. PMID: 40593617.
- [pubmed] Huang Y, et al. "Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes." Front Bioeng Biotechnol, 2021;9:677576. PMID: 33996787.
- [pubmed] Kong YX, et al. "FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation." Commun Biol, 2025;8(1):299. PMID: 39994346.
- [pubmed] Han X, et al. "FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway." J Cell Mol Med, 2022;26(11):3269-3280. PMID: 35510614.
- [pubmed] Zhang C, et al. "FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice." Aging (Albany NY), 2020;12(2):1272-1284. PMID: 31959736.
- [pubmed] Li Y, et al. "FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells." Exp Gerontol, 2024;195:112522. PMID: 39025385.
- [other] US FDA, Drugs@FDA (openFDA): no application for FOXO4-DRI. Read September 30, 2026.
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Guides & tools
This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.