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FOXO4-DRI

FDA: research-only
Last updated · 2026-04-12

Foxo4-DRI (D-Retro-Inverso) is a novel senolytic peptide that selectively targets and neutralizes senescent ("zombie") cells by disrupting the Foxo4-p53 interaction, triggering apoptosis in damaged cells while leaving healthy cells intact. Selectively targets senescent cells by disrupting the interaction between Foxo4 and p53 proteins. In senescent cells, Foxo4 binds p53 to prevent apoptosis, keeping damaged cells alive. Foxo4-DRI competes for this binding, freeing p53 to trigger apoptosis specifically in senescent cells. Healthy cells are unaffected because they don't rely on this survival mechanism. - Selective senescent cell clearance - Anti-aging at the cellular level - Potential cancer protection (removes pre-cancerous senescent

This content is for educational and research purposes only. VialBase does not provide medical advice. Consult a healthcare professional before using any peptide.

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Research summary

Study Type Year Key Finding
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Preclinical study — human tissue expression analysis, in vitro mouse TM3 Leydig cell model, and naturally aged mice (no human dosing) 2020 FOXO4 was specifically expressed in human Leydig cells, and its nuclear translocation in elderly men was associated with decreased testosterone synthesis
Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. In vitro cell culture study using chondrocytes from healthy human donors (no animal or human dosing) 2021 FOXO4-DRI removed more than half of the cells in heavily expanded PDL9 chondrocytes but did not significantly affect cell number in minimally expanded PDL3 controls — demonstrating selectivity for senescent cells
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression. Preclinical mechanistic study (human pulmonary arterial hypertension lung tissue plus mouse and rat pulmonary hypertension models) — safety counter-signal 2023 SAFETY SIGNAL: senolytic elimination of senescent cells — including with FOXO4-DRI specifically — worsened pulmonary hemodynamics and caused marked loss of pulmonary endothelial cells in mouse models
The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Structural biology study — solution NMR of purified protein complexes (in vitro, no cells, animals, or humans) 2025 Solved solution NMR structural models of the p53 transactivation domain in complex with the FOXO4 forkhead domain and, separately, in complex with FOXO4-DRI
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10mg

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Reference ranges are general guidelines. Consult your physician for interpretation.

PRE-CYCLE
  • CMP
  • CBC with differential
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DURING CYCLE
  • CMP
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POST-CYCLE
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Safety & Regulatory Status
FDA STATUS research-only

Regulatory status for FOXO4-DRI may change. Verify current status with your jurisdiction before use. This is not legal or medical advice.

Frequently Asked Questions

What is FOXO4-DRI?
Foxo4-DRI (D-Retro-Inverso) is a novel senolytic peptide that selectively targets and neutrali.
How does FOXO4-DRI work?
Selectively targets senescent cells by disrupting the interaction between Foxo4 and p53 proteins. In senescent cells, Foxo4 binds p53 to prevent apoptosis, keeping damaged cells alive. Foxo4-DRI competes for this binding, freeing p53 to trigger apoptosis specifically in senescent cells.
How is FOXO4-DRI dosed?
Experimental: 5-20 mg intraperitoneally in animal models; No established human protocols; Route: Research only — injection in animal studies. These figures reflect commonly cited research protocols, not medical advice — consult a clinician.
Is FOXO4-DRI FDA-approved?
FOXO4-DRI is a research-only compound and is not FDA-approved. Research-only — no human protocols established; Experimental senolytic compound; Not available through standard suppliers.

References

  1. Zhang C, Xie Y, Chen H, et al.. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.. Aging (2020). PMID: 31959736
  2. Huang Y, He Y, Makarcyzk MJ, et al.. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.. Frontiers in bioengineering and biotechnology (2021). PMID: 33996787
  3. Born E, Lipskaia L, Breau M, et al.. Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.. Circulation (2023). PMID: 36515093
  4. Bourgeois B, Spreitzer E, Platero-Rochart D, et al.. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.. Nature communications (2025). PMID: 40593617