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FOXO4-DRI

FOXO4-p53 interfering peptide

Anti-Aging & LongevityPreclinical
From$5.40/mgCompare prices
MW
5358g/mol
Formula
C228H388N86O64

FOXO4-DRI is a synthetic peptide derived from the forkhead box O transcription factor 4, classified as a senolytic agent due to its ability to selectively induce apoptosis in senescent cells. Researchers primarily study FOXO4-DRI for its potential role in targeting cellular senescence, a process linked to aging and various age-related diseases. Key findings from recent studies indicate that FOXO4-DRI disrupts the interaction between FOXO4 and the tumor suppressor protein p53, leading to the selective elimination of senescent endothelial cells and improved vascular function. Additionally, evidence suggests that FOXO4-DRI effectively reduces senescent cell populations in human chondrocytes, potentially enhancing their regenerative capacity. Current research is focused on elucidating the mechanisms of FOXO4-DRI's action and exploring its applications in various contexts of aging and senescence-related conditions.

Chemical Profile

Chemical Profile

Chemical structure
Chemical Structure
FormulaC228H388N86O64
Molecular Weight5358 g/mol
CAS Number2460055-10-9
PubChem CID167312269

Half-Life

INIntranasal

Not applicable

POOral

Poor bioavailability

Pharmacokinetic properties are still under investigation, with a focus on optimizing delivery methods.

Mechanism

Mechanism of Action

FOXO4-DRI selectively induces apoptosis in senescent cells by disrupting the interaction between FOXO4 and p53, leading to the nuclear exclusion of phosphorylated p53 (p53-pS15) and activation of the p53/BCL-2/Caspase-3 signaling pathway. This mechanism promotes apoptosis and alleviates cellular senescence, particularly in endothelial cells, thereby improving vascular function and delaying vascular aging. The precise details of the receptor interactions and downstream effects remain to be fully elucidated.

Research

14 Research Publications

543

Total Citations

3

Human/RCT

2.3

Avg. Influence

2025

Latest

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#01

Cellular senescence in the aging and diseased kidney.

ReviewInfluence6.0
160
Researchers observed that targeting senescent cells using FOXO4-DRI in experimental models led to improved kidney function and reduced age-associated damage, suggesting a therapeutic approach for renal aging and disease.
PubMed
#02

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.

Born Emmanuelle, et al. · Circulation · 2023

AnimalInfluence6.0
110
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

  1. 01Patients with pulmonary arterial hypertension showed higher levels of senescent cell markers in their lungs compared to healthy controls.
  2. 02In animal models, eliminating senescent cells led to worsened pulmonary blood flow dynamics.
  3. 03The study highlights the need for caution when considering treatments aimed at reducing senescent cells in pulmonary hypertension.
PubMed
#03

Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.

Meng Jingshu, et al. · JCI insight · 2021

AnimalInfluence1.0
109
Researchers observed that FOXO4-DRI effectively radiosensitizes non-small cell lung cancer cells by inducing apoptosis in senescence-like cancer-associated fibroblasts, while also reducing radiation-induced pulmonary fibrosis in mouse models.

Key findings

  1. 01Researchers found that senescence-like fibroblasts promote resistance to radiation in non-small cell lung cancer.
  2. 02The use of a specific peptide, FOXO4-DRI, effectively induced death in these fibroblasts, enhancing the sensitivity of cancer cells to radiation.
  3. 03The study also showed that targeting these fibroblasts reduced lung damage associated with radiation therapy.
PubMed
#04

Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.

Huang Yuzhao, et al. · Frontiers in bioengineering and biotechnology · 2021

UnknownInfluence2.0
46
Researchers observed that FOXO4-DRI effectively removed senescent cells from in vitro expanded human chondrocytes, reducing senescence levels but not significantly enhancing cartilage formation potential.

Key findings

  1. 01Researchers found that FOXO4-DRI selectively eliminates senescent cells.
  2. 02The study observed that removing these cells could enhance the outcomes of cartilage repair procedures.
  3. 03This research suggests a new approach to improve treatments for cartilage injuries and related conditions.
PubMed
#05

FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.

Han Xiaodan, et al. · Journal of cellular and molecular medicine · 2022

AnimalInfluence1.0
34
Researchers observed that FOXO4-DRI ameliorates bleomycin-induced pulmonary fibrosis in mice by decreasing senescent cells and downregulating the expression of the senescence-associated secretory phenotype.

Key findings

  1. 01FOXO4-DRI decreased the number of senescent cells and reduced inflammation in the lungs of mice with pulmonary fibrosis.
  2. 02The peptide improved lung structure by increasing healthy cell types and decreasing harmful myofibroblasts.
  3. 03FOXO4-DRI was shown to disrupt pathways associated with extracellular matrix interactions, which are important in the progression of pulmonary fibrosis.
PubMed
#06

FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.

Kong Yu-Xiang, et al. · Communications biology · 2025

HumanInfluence1.0
23
The study demonstrated that FOXO4-DRI induces apoptosis in keloid senescent fibroblasts by promoting nuclear exclusion of phosphorylated p53, suggesting its potential to target senescence and apoptosis resistance.

Key findings

  1. 01Researchers observed an increase in aging and inflammatory fibroblast cells in keloids.
  2. 02The study found elevated levels of specific proteins associated with cellular aging in keloid tissues.
  3. 03FOXO4-DRI was shown to effectively induce the death of aging fibroblasts, suggesting a new approach to manage keloids.
PubMed
#07

Rejuvenation by Therapeutic Elimination of Senescent Cells.

HumanInfluence1.0
21
The study demonstrated that FOXO4-DRI disrupts the FOXO4-p53 interaction, restoring p53's apoptotic function and ameliorating the consequences of cellular senescence.
PubMed
#08

The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.

Bourgeois Benjamin, et al. · Nature communications · 2025

HumanInfluence2.0
20
The study demonstrated that FOXO4-DRI selectively targets the disordered p53 transactivation domain, enhancing the interaction between FOXO4 and p53, which is crucial for developing p53 inhibitors for diseases linked to cellular senescence.

Key findings

  1. 01Researchers found that the FOXO4-p53 interaction is crucial for the survival of senescent cells.
  2. 02The study identified FOXO4-DRI as a compound that can selectively target these cells.
  3. 03Structural models revealed how FOXO4-DRI binds to the p53 protein, providing insights into their interaction.
PubMed
#09

FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.

Liu Ying, et al. · Naunyn-Schmiedeberg's archives of pharmacology · 2023

Animal
11
The study demonstrated that FOXO4-DRI administration in a bleomycin-induced pulmonary fibrosis mouse model resulted in reduced collagen deposition and milder pathological changes.

Key findings

  1. 01Researchers observed milder lung damage and less collagen deposition in mice treated with FOXO4-D-Retro-Inverso compared to untreated mice.
  2. 02The study found that FOXO4-D-Retro-Inverso altered the distribution of a protein called p53 in lung cells.
  3. 03Researchers noted a decrease in total extracellular matrix proteins in the lungs of mice treated with FOXO4-D-Retro-Inverso.
PubMed
#10

[Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].

Review
5
The study demonstrated that FOXO4-DRI is a promising anti-aging peptide, contributing to the development of anti-aging drugs based on molecular mechanisms of aging.
1200 mg/doral(human)7 d
PubMed
Safety

Safety & Handling

Research Gaps

No randomized controlled human trials evaluating the efficacy and safety of FOXO4-DRI in diverse patient populations have been published. Additionally, the long-term effects of FOXO4-DRI treatment on cellular senescence and its potential impact on tissue regeneration and overall health remain unclear.

Solubility

FOXO4-DRI is soluble in water and DMSO, with limited solubility in organic solvents like acetonitrile.

Storage & Handling

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.

Legal Status

Legal Status

🇩🇪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.

Community Insights

Community Insights

Publications per Year

12 total
3
17
2
21
2
22
1
23
2
25
2
26
Pricing

Price Comparison

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    10mg
    $54.00
    Price/mg
    $5.40/mg
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    $57.15
    Price/mg
    $5.72/mg
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  • PeptiLab USAUS
    10mg
    $77.99
    Price/mg
    $7.80/mg
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  • Ruo BioUS
    10mg
    $100.00
    Price/mg
    $10.00/mg
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  • Peptide CraftersUS
    12mg
    $135.00
    Price/mg
    $11.25/mg
    View

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Mechanism

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Mechanism

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Legal Disclaimer

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