FOXO4

What is FOXO4?

FOXO4-DRI is a synthetic peptide derived from the FOXO4 peptide family and engineered for senescence-related research applications. Unlike native FOXO4, which contributes to the survival of senescent cells, FOXO4-DRI has been developed in experimental models to selectively interfere with senescence-associated signaling pathways. This peptide incorporates D-amino acids (mirror-image amino acids) in its design, enhancing enzymatic stability and resistance to proteolytic degradation, making it suitable for controlled laboratory investigations. FOXO4-DRI has a molecular weight of approximately 5358.05 g/mol (~5.36 kDa) and consists of an extended amino acid sequence designed for structural stability and functional activity in experimental systems. Research involving FOXO4-DRI generally focuses on cellular senescence pathways, oxidative stress mechanisms, transcriptional regulation, and stress-associated signaling processes.

Product Specifications

• Product Name: FOXO4-DRI
• CAS Number: 2460055-10-9
• Chemical Formula: C228H388N86O64
• Subscript Format: C₂₂₈H₃₈₈N₈₆O₆₄
• Molecular Weight: 5358.05 g/mol
• Sequence: LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG
• Peptide Length: 30 amino acids
• Structure Type: D-amino acid–modified peptide (DRI configuration)

What are the key features of FOXO4?

FOXO4-DRI is supplied as a lyophilized powder in sterile vials, making it easy to handle and store for research use. The peptide is manufactured to ensure high purity, typically ≥95%, and is verified through standard analytical methods such as HPLC and mass spectrometry. This format ensures reproducibility and consistency across experimental conditions.

Key Features:

• Synthetic peptide modeled after a functional FOXO4 domain
• High purity (≥ 95%) verified through HPLC and mass spectrometry
• Lyophilized powder for stability and ease of reconstitution
• Investigated for cellular senescence, oxidative stress, and metabolic regulation
• Packaged in sealed vials suitable for research applications
• For laboratory research use only

Researchers who buy FOXO4 generally use it for studying senolytic mechanisms, oxidative stress responses, and protein transcription in various models.

How is FOXO4 synthesized?

FOXO4-DRI is produced using solid-phase peptide synthesis (SPPS), a method that allows for precise assembly of the peptide's 29–30 amino acids. The peptide backbone is synthesized with L-amino acids and then inverted into D-amino acids to form the D-retro-inverso (DRI) version, which enhances enzymatic stability and efficacy in research settings. After synthesis, FOXO4-DRI undergoes purification by high-performance liquid chromatography (HPLC), followed by mass spectrometry (MS) to verify the peptide's purity and molecular integrity. This process ensures that the synthetic peptide behaves predictably in experimental models, aligning with published FOXO4-DRI research. The D-amino acid modification makes FOXO4-DRI more stable in vitro and more effective in senolytic applications than the native FOXO4 peptide.

What is FOXO4 being studied for? What are its possible benefits?

FOXO4-DRI is primarily studied as a senolytic agent for cellular senescence, which involves the removal of senescent cells that accumulate with age. Research has investigated FOXO4-DRI's role in oxidative stress, cellular repair, and metabolic processes. It is under investigation for its potential to regulate cellular functions involved in protein synthesis, cell cycle arrest, and DNA damage response pathways. FOXO4-DRI blocks the FOXO4-p53 interaction, which typically helps senescent cells survive. By blocking this interaction, FOXO4-DRI promotes the removal of these damaged cells, improving tissue health. All observations remain preliminary and are confined to controlled research environments. No clinical outcomes have been established, and FOXO4-DRI is not intended for human use.

How does FOXO4 work in research studies?

In research settings, FOXO4-DRI is studied for its ability to eliminate senescent cells by modulating the FOXO4-p53 interaction. This interaction is crucial in protecting senescent cells, but FOXO4-DRI blocks it, promoting the removal of damaged cells from tissues. FOXO4-DRI has been examined for its senolytic effect in various cellular models, targeting proteins and pathways involved in cellular maintenance, oxidative stress, and DNA damage repair. These studies primarily focus on how FOXO4-DRI modulates cellular processes related to senescence and stress resistance, helping to understand the peptide's potential in rejuvenating aged tissues or impaired biological systems.

What dosing information exists for FOXO4?

The FOXO4-DRI peptide is investigated at varying concentrations depending on the research model and experimental focus. Preclinical studies have used a range of concentrations, including:

• In vivo murine models: 5–10 mg/kg (micrograms per kilogram body weight)
• In vitro cellular assays: 1–20 µM (micromolar concentrations)

Note: These concentrations are from FOXO4-DRI preclinical studies only and should not be extrapolated to human or animal use.

How should FOXO4 be stored and handled?

FOXO4-DRI should be stored in lyophilized form at –20 °C or lower, protected from light and moisture to preserve peptide stability. Upon reconstitution, the peptide should be stored at 2–8 °C for short-term use, with aliquoting recommended to avoid repeated freeze-thaw cycles. Researchers using FOXO4-DRI should follow standard peptide-handling protocols, including sterile technique, proper PPE, and controlled environmental conditions to ensure reproducibility in experiments. FOXO4-DRI typically remains stable for 6–12 months when stored properly under the specified conditions.

Where can I read more research about FOXO4?

Researchers interested in exploring FOXO4-DRI and its potential senolytic activity can consult the following peer-reviewed sources:

1. 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
2. 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
3. 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

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

Compliance Statement

This product is intended for laboratory research use only and is not approved for human or veterinary use.