FOXO4-DRI (10mg) Research Peptide: A D‑Retro‑Inverso Senolytic Peptide for Cellular Senescence & Aging Studies

If your research investigates the molecular mechanisms of cellular senescence, the biology of aging, or the selective elimination of damaged cells, FOXO4-DRI (10mg) research peptide offers a precisely defined and extensively studied synthetic tool. FOXO4-DRI is a cell‑permeable, D‑retro‑inverso (DRI) peptide derived from the forkhead box O4 (FOXO4) transcription factor. It was first reported in a landmark 2017 study by Baar et al. in Cell, which demonstrated that the peptide could selectively induce apoptosis in senescent cells and restore tissue homeostasis.

By specifically disrupting the protein‑protein interaction between FOXO4 and the tumour suppressor p53, FOXO4-DRI enables researchers to study the role of the FOXO4‑p53 axis in maintaining the viability of senescent cells. This makes FOXO4-DRI (10mg) research peptide a valuable tool for laboratories investigating cellular senescence, aging biology, apoptosis pathways, fibrosis, and regenerative medicine.

At Chinese Grey Peptides, we supply high‑purity FOXO4-DRI (10mg) research peptide to research institutions and wholesale buyers across the United Kingdom, France, Germany, Spain, Sweden, Italy, and the USA. Every batch is lyophilised, HPLC‑verified to >98% purity, and accompanied by a Certificate of Analysis (COA), ensuring your investigations into senescence, aging, apoptosis, and fibrosis begin with uncompromising quality.

What Is FOXO4‑DRI and How Does It Work?

To fully appreciate the research potential of FOXO4-DRI (10mg) research peptide, it is essential to understand its biochemical design and the precise mechanism by which it exerts its selective senolytic effects.

The D‑Retro‑Inverso Peptide

FOXO4-DRI is a synthetic peptide composed entirely of D‑amino acids in a retro‑inverso configuration. Its sequence is D‑(LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG), consisting of 46 amino acids. The peptide has a molecular formula of C₂₂₈H₃₈₈N₈₆O₆₄, a molecular weight of approximately 5358.06 Da, and a CAS number of 2460055-10-9.

The peptide incorporates a cell‑penetrating sequence derived from the HIV‑TAT protein, which facilitates its entry into cells. The D‑retro‑inverso configuration confers enhanced resistance to proteolytic degradation, making the peptide more stable in biological systems compared to L‑amino acid peptides.

Mechanism of Action: Selective Senolytic Activity via FOXO4‑p53 Disruption

The biological activity of FOXO4-DRI (10mg) research peptide is mediated through its targeted disruption of the FOXO4‑p53 protein‑protein interaction:

• FOXO4‑p53 Axis Disruption: FOXO4-DRI specifically disrupts the interaction between FOXO4 and p53. In senescent cells, FOXO4 binds p53 in the nucleus, preventing p53 from inducing apoptosis and maintaining the senescent cell in a state of growth arrest. FOXO4-DRI displaces endogenous FOXO4 from p53, breaking this interaction.

• p53 Nuclear Exclusion: By disrupting the FOXO4‑p53 complex, FOXO4-DRI facilitates the nuclear export of phosphorylated p53. This relocalisation of p53 away from the nucleus is a critical step in triggering apoptosis.

• Activation of the p53/BCL‑2/Caspase‑3 Pathway: The nuclear exclusion of phosphorylated p53 subsequently triggers the activation of BAX and cleaved caspase‑3, leading to the activation of the p53/BCL‑2/Caspase‑3 signalling pathway. This cascade promotes the selective apoptosis of senescent cells.

• Reduction of Senescence‑Associated Secretory Phenotype (SASP): FOXO4-DRI reduces the secretion of the senescence‑associated secretory phenotype (SASP) from senescent cells, which in turn improves the surrounding cellular microenvironment.

Research Note: Structural Basis of FOXO4‑DRI Action

A 2025 study published in Nature Communications provided detailed structural characterisation of the FOXO4‑DRI interaction. The study found that the disordered FOXO4‑DRI binds to the disordered p53TAD2 domain and forms a transiently folded complex. Furthermore, p53 phosphorylation enhances the affinity for both FOXO4 and FOXO4-DRI. This structural insight provides a molecular basis for the peptide’s selective activity in senescent cells.

Key Research Applications for FOXO4‑DRI (10mg)

FOXO4-DRI (10mg) research peptide is a versatile tool with applications spanning several domains of biomedical research.

1. Cellular Senescence & Aging Research

The most established application of FOXO4-DRI lies in its ability to serve as a selective senolytic agent for studying cellular senescence and aging. Research has demonstrated:

• Endothelial Cell Senescence: FOXO4-DRI induces apoptosis in senescent endothelial cells and significantly improves vascular function, delaying vascular aging.

• Vascular Aging Models: Injection of FOXO4-DRI in naturally aged and induced aging mice effectively suppressed aortic aging and improved aortic function.

• Testicular Aging: FOXO4-DRI improves spermatogenesis in aged mice by reducing SASP secretion from senescent Leydig cells.

• Age‑Related Testosterone Decline: FOXO4-DRI alleviates age‑related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.

2. Fibrosis & Scarring Research

FOXO4-DRI has demonstrated potential in fibrosis and scarring research:

• Keloid Research: FOXO4-DRI promotes apoptosis in keloid senescent fibroblasts by promoting nuclear exclusion of upregulated p53‑serine 15 phosphorylation. This highlights the role of the senescent microenvironment in keloid overgrowth and relapse.

• Pulmonary Fibrosis: FOXO4-DRI decreases senescent cells and attenuates bleomycin‑induced morphological changes and collagen deposition in mouse models.

3. Cartilage & Osteoarthritis Research

FOXO4-DRI has been investigated for its potential in cartilage research:

• Chondrocyte Senescence: FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes, potentially enhancing their potential for generating high‑quality cartilage.

4. Apoptosis & Signal Transduction Research

As a precise modulator of the FOXO4‑p53 interaction, FOXO4-DRI serves as a research tool for dissecting apoptosis pathways:

• Apoptosis Pathway Investigation: FOXO4-DRI is instrumental in dissecting the molecular determinants of programmed cell death.

• Signal Transduction Analysis: FOXO4-DRI serves as a precise modulator for delineating the downstream effects of FOXO transcription factors and studying the cross‑talk between stress response pathways and apoptotic regulators.

5. Senolytic & Anti‑Senescence Research

FOXO4-DRI is widely utilised in studies investigating the molecular mechanisms underlying cellular senescence:

• Selective Senescent Cell Elimination: By selectively interfering with the endogenous FOXO4‑p53 binding, the peptide enables researchers to induce targeted disruption of senescence‑associated signalling pathways.

• Tissue Homeostasis Studies: FOXO4-DRI facilitates studies aimed at understanding how the accumulation or removal of senescent cells impacts aging phenotypes and tissue regeneration.

Chemical & Physical Specifications for FOXO4-DRI (10mg)

Accurate characterisation of FOXO4-DRI (10mg) research peptide is essential for reproducible experimental design.

Note: The 10 mg mass refers to the weight of the peptide in its lyophilised form. FOXO4-DRI is typically supplied as a TFA or acetate salt, which enhances aqueous solubility. The peptide contains a cell‑penetrating sequence derived from HIV‑TAT. The peptide is for research use only (RUO). Not for human consumption. FOXO4-DRI is not FDA‑approved for therapeutic use.

Reconstitution & Handling Protocol for FOXO4-DRI (10mg)

Proper reconstitution of FOXO4-DRI (10mg) research peptide is critical for maintaining its structural integrity and biological activity. The D‑retro‑inverso configuration confers enhanced stability, but standard peptide handling precautions should still be observed.

Step 1 – Preparation

• Bring the sealed FOXO4-DRI vial and your chosen diluent (sterile bacteriostatic water or sterile PBS, pH 5‑7) to room temperature. Condensation can degrade the lyophilised powder.

• Clean your work surface with 70% ethanol and lay out sterile syringes, alcohol wipes and a clean work mat.

Step 2 – Vial Sanitisation

• Wipe the rubber stopper of the FOXO4-DRI vial with a fresh 70% ethanol wipe. Allow the alcohol to evaporate completely before piercing.

Step 3 – Reconstitution

• Draw your desired volume of diluent into a sterile syringe. A common starting concentration for research applications is 10 mg per 1 mL of diluent, yielding a 10 mg/mL stock solution.

• Insert the needle and slowly inject the diluent against the inner glass wall. Do not spray directly onto the lyophilised powder.

• Gently swirl the vial until the solution is clear and fully dissolved. Do not shake vigorously, as shaking can cause denaturation.

Step 4 – Aliquoting & Storage

• Immediately after dissolution, aliquot the reconstituted FOXO4-DRI into single‑use sterile vials.

• Store aliquots at –20°C. Avoid repeated freeze‑thaw cycles, as peptides are susceptible to degradation.

• Once thawed, store at 2‑8°C and use within a short period.

Concentration Reference Table for FOXO4-DRI (10mg)

Adjust diluent volume based on your experimental requirements. For cell culture applications, typical working concentrations may range from 0.1‑10 µM.

Storage & Stability Guidelines for FOXO4-DRI (10mg)

Why Choose Chinese Grey Peptides for FOXO4-DRI (10mg)?

As an authentic licensed peptide supplier based in the USA, we supply FOXO4-DRI (10mg) research peptide and a wide range of research‑grade compounds under rigorous quality assurance protocols, fully aligned with Google’s E‑E‑A‑T standards (Experience, Expertise, Authoritativeness, Trustworthiness).

• Verified Purity: Independent HPLC analysis with purity guaranteed >98% for every batch.

• GMP‑Compliant Manufacturing: All peptides are synthesised under strict quality control conditions.

• Full Traceability: Batch‑specific Certificates of Analysis (COA) are available for every order.

• Wholesale Supply: We serve research institutions, laboratories, and wholesale buyers across the UK, EU, and USA with flexible volume pricing and reliable logistics.

• USA‑Based Regulatory Compliance: All products are supplied strictly as research‑grade chemicals for laboratory use only (RUO). FOXO4-DRI is not FDA‑approved for therapeutic use.

Researchers across the United States—including those at leading institutions—trust us for fast domestic delivery, transparent documentation and professional technical support.

FAQ: FOXO4-DRI (10mg) Research Peptide

What is FOXO4-DRI (10mg) research peptide?
FOXO4-DRI is a synthetic, cell‑permeable D‑retro‑inverso (DRI) peptide derived from the forkhead box O4 (FOXO4) transcription factor. It is designed to disrupt the interaction between FOXO4 and p53, selectively inducing apoptosis in senescent cells. Its D‑retro‑inverso configuration confers enhanced resistance to proteolytic degradation.

What is the sequence and molecular weight of FOXO4-DRI?
The sequence is D‑(LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG). Its molecular formula is C₂₂₈H₃₈₈N₈₆O₆₄, and its molecular weight is approximately 5358.06 Da. It has a CAS number of 2460055-10-9.

What are the primary research applications for FOXO4-DRI?
FOXO4-DRI is used in cellular senescence and aging research (endothelial cell senescence, vascular aging, testicular aging), fibrosis and scarring research (keloids, pulmonary fibrosis), cartilage and osteoarthritis research (chondrocyte senescence), apoptosis and signal transduction research, and senolytic and anti‑senescence research.

What is the mechanism of action of FOXO4-DRI?
FOXO4-DRI specifically disrupts the interaction between FOXO4 and p53. In senescent cells, FOXO4 binds p53 in the nucleus, preventing p53‑induced apoptosis. FOXO4-DRI displaces FOXO4 from p53, facilitating the nuclear export of phosphorylated p53, which triggers BAX and cleaved caspase‑3 and activates the p53/BCL‑2/Caspase‑3 pathway, leading to selective apoptosis of senescent cells.

What is the structural basis of FOXO4-DRI action?
A 2025 study in Nature Communications found that FOXO4-DRI binds to the disordered p53TAD2 domain and forms a transiently folded complex. p53 phosphorylation enhances the affinity for both FOXO4 and FOXO4-DRI.

What purity does your FOXO4-DRI (10mg) meet?
Our FOXO4-DRI is tested to >98% purity by HPLC. A Certificate of Analysis (COA) is supplied with every order.

How should I reconstitute FOXO4-DRI (10mg)?
Reconstitute with sterile bacteriostatic water or sterile PBS (pH 5‑7). Allow the vial to reach room temperature, then slowly inject the diluent against the inner glass wall and swirl gently. Do not shake. A typical starting concentration is 10 mg/mL.

How should I store reconstituted FOXO4-DRI?
Reconstituted FOXO4-DRI should be stored at 2‑8°C for short‑term use. For longer storage, aliquot immediately into single‑use vials and store at –20°C for up to 6 months. Avoid repeated freeze‑thaw cycles.

Is FOXO4-DRI research peptide legal to purchase in the USA?
Yes. FOXO4-DRI is a laboratory reagent sold for research use only (RUO). It is fully legal to purchase, possess, and use in the United States for legitimate in‑vitro or in‑vivo scientific research, provided it is not marketed with therapeutic claims. Note: FOXO4-DRI is not FDA‑approved for therapeutic use and is supplied for research purposes only.

 Does Chinese Grey Peptides ship internationally?
Yes. We ship across the UK, Europe (France, Germany, Spain, Sweden, Italy), and the USA from our US warehouse. Wholesale pricing is available for bulk orders.

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Important Compliance Notice

FOXO4-DRI (10mg) may be regulated differently depending on the country, product type, labeling, intended use, buyer type, and destination. Chinese Grey Peptides does not provide medical advice, dosing instructions, injection guidance, IV guidance, anti-aging claims, energy claims, longevity claims, detox claims, mitochondrial claims, disease claims, treatment claims, or personal-use recommendations.

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From its discovery as a selective senolytic peptide in a landmark 2017 Cell publication to its well‑characterised role in disrupting the FOXO4‑p53 interaction and inducing apoptosis in senescent cells, FOXO4-DRI (10mg) research peptide provides a precisely defined and extensively validated platform for advanced senescence and aging research. Its ability to selectively eliminate senescent cells, reduce SASP secretion, and improve tissue function in models of vascular aging, testicular aging, pulmonary fibrosis, and keloid scarring—supported by a growing body of peer‑reviewed research published in Cell, Nature Communications, Frontiers, and other authoritative journals—makes it a valuable addition to any laboratory investigating cellular senescence, the biology of aging, fibrosis, or regenerative medicine.

By choosing high‑purity, lab‑verified FOXO4-DRI (10mg) research peptide from Chinese Grey Peptides, you ensure that your research is built on a foundation of quality, reproducibility, and scientific integrity.

Ready to advance your research with FOXO4-DRI (10mg)? Browse our product catalogue, request a wholesale quote, or contact our support team today to discuss your laboratory’s specific needs. Place your order now and receive GMP‑grade FOXO4-DRI delivered directly to your facility in the USA, UK, or Europe.