FOXO4-DRI

also known as: FOXO4-p53 interfering peptide, FOXO4 DRI

A D-retro-inverso cell-penetrating peptide designed by the Peeper lab (Netherlands Cancer Institute) to selectively clear senescent cells — the prototype senolytic peptide.

A protease-resistant D-retro-inverso peptide that disrupts the FOXO4-p53 interaction in senescent cells, releasing p53 to trigger apoptosis selectively in the senescent compartment while sparing normal cells — a landmark 2017 Cell paper established the proof of concept.

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

preclinical intermittent (intraperitoneal (preclinical))

No human dosing established. Community use carries substantial unknown risk given the pro-apoptotic mechanism.

Regulatory status

Not approved. Preclinical-stage research peptide with a prominent 2017 Cell publication demonstrating senescent cell clearance and functional improvement in aged mice. No human clinical trials.

References

[pubmed] Baar MP, et al. "Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging." Cell, 2017;169:132-147.e16.

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Disclaimer

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.