FOXO4-p53 interfering peptide
FOXO4-DRI is a senolytic peptide derived from the forkhead box O transcription factor 4, designed to selectively target and eliminate senescent cells. Researchers primarily study FOXO4-DRI for its potential role in alleviating the negative effects of cellular senescence in various pathological conditions, including cancer and pulmonary fibrosis. Key findings from recent studies indicate that FOXO4-DRI can induce apoptosis in senescent fibroblasts, thereby reducing their proliferation and enhancing the efficacy of cancer therapies, while also mitigating radiation-induced pulmonary fibrosis. Additionally, preclinical evidence suggests that FOXO4-DRI effectively removes senescent cells from expanded chondrocytes, potentially improving their regenerative capacity. Current research is focused on further elucidating the mechanisms of FOXO4-DRI and exploring its applications in treating age-related diseases and conditions associated with cellular senescence.
| Formula | C228H388N86O64 |
| Molecular Weight | 5358 g/mol |
| CAS Number | 2460055-10-9 |
| PubChem CID | 167312269 |
Not applicable
Poor bioavailability
Pharmacokinetic properties are still under investigation, with a focus on optimizing delivery methods.
FOXO4-DRI selectively induces apoptosis in senescent cells by disrupting the interaction between FOXO4 and the disordered transactivation domain of p53, leading to nuclear exclusion of phosphorylated p53 (p53-pS15) and promoting cell death. This mechanism involves the modulation of the p53 signaling pathway, which is critical for maintaining cellular senescence and apoptosis resistance. While the precise details of the signaling cascades involved remain to be fully elucidated, FOXO4-DRI's action highlights its potential in targeting senescence-related pathologies.
461
Total Citations
3
Human/RCT
2.8
Avg. Influence
2025
Latest
The study demonstrated that FOXO4-DRI induces forced apoptosis of senescent cells, leading to improved kidney function during aging in animal models.
Meng Jingshu, et al. · JCI insight · 2021
The study demonstrated that specific induction of apoptosis in senescence-like cancer-associated fibroblasts using FOXO4-DRI radiosensitized non-small cell lung cancer and reduced radiation-induced pulmonary fibrosis in vivo.
Key findings
Born Emmanuelle, et al. · Circulation · 2023
Researchers observed that the elimination of senescent pulmonary endothelial cells by senolytic interventions may worsen pulmonary hemodynamics in mouse models of pulmonary arterial hypertension.
Key findings
Huang Yuzhao, et al. · Frontiers in bioengineering and biotechnology · 2021
The study demonstrated that FOXO4-DRI effectively removed senescent cells from in vitro expanded human chondrocytes, reducing their senescence level without enhancing their chondrogenic potential.
Key findings
Han Xiaodan, et al. · Journal of cellular and molecular medicine · 2022
Researchers observed that FOXO4-DRI reduces senescent cells and collagen deposition in a bleomycin-induced pulmonary fibrosis mouse model, suggesting its potential as a therapeutic option.
Key findings
The study demonstrated that FOXO4-DRI disrupts the FOXO4-p53 interaction, restoring p53's apoptotic function and ameliorating the effects of cellular senescence.
Bourgeois Benjamin, et al. · Nature communications · 2025
Researchers observed that FOXO4-DRI binds to the disordered p53 transactivation domain, enhancing the understanding of how to selectively target senescent cells for potential therapeutic applications.
Key findings
Kong Yu-Xiang, et al. · Communications biology · 2025
Researchers observed that FOXO4-DRI induces apoptosis in keloid senescent fibroblasts by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation, suggesting its potential in targeting keloid aggressiveness.
Key findings
Liu Ying, et al. · Naunyn-Schmiedeberg's archives of pharmacology · 2023
The study demonstrated that FOXO4-DRI ameliorates bleomycin-induced pulmonary fibrosis in mice by decreasing collagen deposition and resetting the distribution of intranuclear p53.
Key findings
Researchers observed that FOXO4-DRI, among other anti-aging drugs, shows promise in regulating molecular mechanisms of aging, potentially contributing to anti-aging therapies.
No randomized controlled human trials have been conducted to assess the efficacy and safety of FOXO4-DRI in humans. Additionally, the long-term effects of FOXO4-DRI treatment on cellular senescence and overall tissue health remain unclear, particularly in the context of chronic conditions such as pulmonary hypertension and keloids. Furthermore, the precise molecular mechanisms by which FOXO4-DRI induces apoptosis in various senescent cell types are not fully elucidated, particularly regarding its interaction with p53 and other signaling pathways involved in cellular senescence.
Solubility
FOXO4-DRI is soluble in water and DMSO, with limited solubility in organic solvents like acetonitrile.
Lyophilized
Stable for 2+ years at -20°C, 12 months at 4°C
Reconstituted
Use within 14 days when refrigerated at 4°C
Avoid
Avoid repeated freeze-thaw cycles, direct light
Solvent
Bacteriostatic water or sterile saline recommended
Safety information is derived from published research and may not reflect all known risks. This is not medical advice.
🇩🇪DE
Not approved as a medicinal product. Not a controlled substance. Sale as research chemical is a legal grey area.
🇺🇸US
Not approved by the FDA. Not scheduled by the DEA.
🇦🇺AU
Not listed in the TGA schedules.
🇬🇧UK
Not approved by the MHRA for medicinal use.
Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.
Publications per Year
11 total| Vendor | Amount | Price | Price/mg | Link |
|---|---|---|---|---|
BESTRCpeptidesEU | 10mg | $54.00 | $5.40/mg | |
XL PeptidesUK | 10mg | $88.89 | $8.89/mg | |
Ion PeptideUS | 10mg | $119.00 | $11.90/mg | |
Glacier AminosUS | 10mg | $134.99 | $13.50/mg | |
Peptide CraftersUS | 12mg | $165.00 | $13.75/mg |
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This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer