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Evidence profile · Longevity & Cellular Aging

FOXO4-DRI

FOXO4-DRI is a senolytic research reagent. Mouse data exist. No human trial exists.

EvidenceEmergingRegulatoryResearch use onlyWADANot named

Checked by the PU Research editorial teamevidence-graded against primary sources. Last check: 23 July 2026. Sources: 3. Who checks this

01

Identity & Classification

FOXO4-DRI is a D-retro-inverso peptide with about 46 residues. It is a senolytic research reagent.

02

Mechanism: How It Works

FOXO4-DRI disrupts the interaction between FOXO4 and p53 through competition. This forces p53 out of the nucleus.

The result is apoptosis that depends on p53 and p21. The effect is selective for senescent cells, because those cells overexpress FOXO4.

03

Research Findings

Evidence tier: preclinical only.

Baar et al. (Cell, 2017) reported a decreased senescent-cell burden in mice. The same work reversed doxorubicin chemotoxicity. It improved fur density, kidney function, and activity in naturally aged mice and in progeroid mice.

Later NMR work (Nature Communications, 2025) confirmed binding at the p53 TAD2 site, with a Kd of about 400 nM.

Evidence limit. No human trial exists. An improved analog, CL04183, is still preclinical.

04

Reported Dosing & Delivery

No high-authority human dosing exists. It is a research reagent only.

05

Pharmacokinetics & Timing

No source specifies the serum half-life. No source specifies the immunogenicity.

06

Interactions & Combinations

No documented interaction exists.

Compare with Epithalon and Humanin.

07

Safety & Contraindications

No human data exist.

08

Monitoring & Biomarkers

No validated biomarker exists.

09

Regulatory Status

No regulator approves it. It is for research use only. No registered human trial exists. WADA does not name it.

10

Works Cited

  1. 01Baar MP, et al. "Targeted apoptosis of senescent cells...". Cell, 2017. View source →
  2. 02AACR Cancer Discovery summary.
  3. 03Nature Communications, 2025 (p53 TAD2 binding). View source →

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