FOXO4

What is FOX04DRI (10mg)?

FOXO4-DRI (10 mg) is a synthetic, all-D “retro-inverso” research peptide based on a region of FOXO4 that can interact with the tumor suppressor p53 in senescent (aging-like) cells. In many experimental systems, the FOXO4–p53 interaction helps senescent cells stay alive, which makes it a useful target in senescence and senolytic-style research.

Classified under longevity and anti-aging peptides, FOXO4-DRI competes with the body’s own FOXO4 for p53 binding. In preclinical studies (cell culture and mouse models), researchers have reported that this can trigger apoptosis (programmed cell death) mainly in senescent cells, with less impact on non-senescent controls under the tested conditions.

Researchers use FOXO4-DRI to explore how reducing senescent-cell burden may affect inflammation, tissue function, and repair in controlled models.

Additionally, this material is a research tool only and has no approved clinical indications.

Product Specifications

• Synonyms: FOXO4-DRI; FOXO4 D‑Retro‑Inverso peptide; Proxofim
• Chemical Formula: C₂₂₈H₃₈₈N₈₆O₆₄
• Molecular Weight: 5358.05 g/mol
• CAS Number: 2460055-10-9​
• Peptide Sequence (one‑letter code): LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG
• Purity: Typically supplied at ≥95% purity by HPLC; lot‑specific purity and analytical data (HPLC, MS) are documented on the Certificate of Analysis.
• Packaging Format: 10 mg FOX04DRI per vial, provided as a lyophilized (freeze‑dried) powder in a sealed research‑grade container.
• Storage Conditions: Store at −20°C or below, protected from light and moisture; avoid repeated freeze–thaw cycles.
• Intended Use: For Laboratory Research Use Only (not for human or veterinary use).

Key Characteristics of FOX04DRI (10mg)

• All-D Retro-Inverso Design: Uses D-amino acids to improve resistance to enzymatic breakdown compared with typical L-peptides.
• Cell-Entry Support: An arginine-rich tail helps cellular uptake and supports access to intracellular targets in experimental systems.
• Targets a Senescent-Cell Survival Interaction: Competes with FOXO4 for p53 binding, disrupting a pathway linked to senescent-cell persistence in preclinical models.
• Senescence-Focused Readouts: Studies that reduce senescent-cell burden with FOXO4-DRI have reported changes in selected tissue integrity and functional markers in animal models.
• Research-Only Format: Supplied as a high-purity, lyophilized reagent for in-vitro and preclinical in-vivo work, not for diagnostic or therapeutic use.

How FOX04DRI (10mg) Supports Research

Researchers use FOXO4-DRI to study how selective removal of senescent cells can influence tissue function, regeneration, inflammation, and response to stress in defined models. It is commonly applied in senescence paradigms created by DNA damage, oncogene signaling, extended cell culture, or cytotoxic treatments.

FOXO4-DRI also serves as a practical probe for FOXO4–p53 biology, helping researchers examine binding behavior, p53 localization, and downstream apoptotic signaling in senescent cells.

Research Applications & Usage Information

FOXO4‑DRI (10 mg) is commonly included in laboratory studies focused on:

• Cellular senescence models (fibroblasts, epithelial cells, primary cultures) to assess selective senescent‑cell elimination, SASP cytokines, and bystander effects.
• Chemotherapy‑ or radiation‑induced senescence in mice, to study how senescent‑cell removal influences tissue damage, functional decline, and recovery.
• Cartilage and chondrocyte systems, investigating senescent‑cell clearance effects on matrix enzymes, senescence markers, and gene expression.
• Preclinical reproductive and endocrine aging models, including spermatogenesis studies probing Leydig‑cell senescence and SASP‑linked microenvironments.
• Computational and structural studies of FOXO4–p53, plus comparative senolytic research alongside small‑molecule senolytics and other approaches.
• Broader geroscience and aging studies: Exploring how altering senescent‑cell burden influences organ‑specific or systemic aging phenotypes in animal models, always within controlled preclinical experiments.

Across these applications, FOXO4‑DRI is employed as a mechanistic probe to test hypotheses about senescent cells and aging biology. Observed outcomes are specific to the models and conditions studied and should not be interpreted as evidence of safety or efficacy in humans.

Handling and Storage Recommendations

To preserve the quality and reproducibility of FOXO4‑DRI (10 mg):

• Keep sealed vials at −20 °C or colder, dry, and protected from light.
• Let the sealed vial reach room temperature to reduce condensation.
• Store 2-8 °C (short-term) or −20 °C (long-term) per your lab’s validated practice.
• Properly discard if cloudy, discolored, or particulate, in accordance to the institutional chemical/biohazard waste procedures.

Research Use Only Notice

This product is intended for laboratory research use only and is not approved for human or veterinary use. It is not intended for diagnostic, therapeutic, or clinical applications. Any reference to biological activity or potential effects is based solely on preclinical or in-vitro findings and should not be interpreted as validated clinical outcomes. Researchers are responsible for ensuring proper handling, storage, and disposal in accordance with institutional, federal, and international guidelines.

References

1. Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell. 2017;169(1):132-147.e16. doi:10.1016/j.cell.2017.02.031
2. Huang Y, He Y, Makarcyzk MJ, Lin H. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Frontiers in Bioengineering and Biotechnology. 2021;9:677576. doi:10.3389/fbioe.2021.677576
3. 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;12(2):1272-1284. doi:10.18632/aging.102682
4. Le HH, Cinaroglu SS, Manalo EC, et al. Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells. EBioMedicine. 2021;73:103646. doi:10.1016/j.ebiom.2021.103646
5. 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;16(1):5672. doi:10.1038/s41467-025-60844-9