Mitochondrial & longevity research compounds
FOXO4-DRI
Also known as FOXO4 D-retro-inverso peptide · proxofim
A D-retro-inverso peptide designed to disrupt the FOXO4–p53 interaction that keeps senescent cells alive — a senolytic research tool.
In 60 seconds
Preclinical (aged and chemotoxicity mouse models, Leydig and endothelial senescence, keloid fibroblasts). No human safety data; a 2023 study found eliminating senescent cells can worsen pulmonary hypertension in animal models, a caution for senolytics broadly.
- The discovery study: a FOXO4 peptide induced apoptosis of senescent cells and restored tissue homeostasis in mice.
- Mapped FOXO4-DRI’s target to the disordered p53 transactivation domain.
- In aged mice, FOXO4-DRI targeted senescent Leydig cells and improved testosterone secretion.
Mechanism
In senescent cells, FOXO4 binds p53 and holds it in the nucleus, preventing apoptosis. FOXO4-DRI competes for that interaction, releasing p53 to trigger death of senescent cells selectively.
Research status
Preclinical (aged and chemotoxicity mouse models, Leydig and endothelial senescence, keloid fibroblasts). No human trials published.
Key studies
The discovery study: a FOXO4 peptide induced apoptosis of senescent cells and restored tissue homeostasis in mice.
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging — Cell, 2017 · PMID 28340339
Mapped FOXO4-DRI’s target to the disordered p53 transactivation domain.
The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI — Nat Commun, 2025 · PMID 40593617
In aged mice, FOXO4-DRI targeted senescent Leydig cells and improved testosterone secretion.
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice — Aging (Albany NY), 2020 · PMID 31959736
Found that clearing senescent cells can promote pulmonary hypertension in animal models.
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression — Circulation, 2023 · PMID 36515093
Safety signals in the literature
No human safety data; a 2023 study found eliminating senescent cells can worsen pulmonary hypertension in animal models, a caution for senolytics broadly.
Legal status (South Africa)
Research compounds; not registered medicines for human use in South Africa unless stated otherwise.
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Comparisons
Questions
What is FOXO4-DRI?
A D-retro-inverso peptide designed to disrupt the FOXO4–p53 interaction that keeps senescent cells alive — a senolytic research tool. In senescent cells, FOXO4 binds p53 and holds it in the nucleus, preventing apoptosis. FOXO4-DRI competes for that interaction, releasing p53 to trigger death of senescent cells selectively.
What is the research status of FOXO4-DRI?
Preclinical (aged and chemotoxicity mouse models, Leydig and endothelial senescence, keloid fibroblasts). No human trials published.
What safety signals are reported for FOXO4-DRI?
No human safety data; a 2023 study found eliminating senescent cells can worsen pulmonary hypertension in animal models, a caution for senolytics broadly.
Does Living Water Labs stock FOXO4-DRI?
Not at present. FOXO4-DRI is profiled here for reference, with citations to the published literature. You can ask to be notified if we add it. Research compounds; not registered medicines for human use in South Africa unless stated otherwise.
More in Mitochondrial & longevity
Research reference only. This page summarises published literature; it is not medical advice and contains no guidance on human use. Products supplied by Living Water Labs are for laboratory research only.
