FOXO4-DRI Senolytic Peptide

FOXO4-DRI – Cell-Permeable Senolytic Peptide for Aging and Senescence Research

Basic Information

• CAS Number: 2460055-10-9

• Molecular Formula: C₂₂₈H₃₈₈N₈₆O₆₄

• Molecular Weight: 5358.06 g/mol

• Appearance: White lyophilized powder

• Purity: ≥98% (HPLC)

• Sequence (all D‑amino acids): D‑(LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG)

• Storage: Store at –20°C, protected from light and moisture

Overview
FOXO4-DRI (D‑Retro‑Inverso) is a synthetic, cell‑permeable peptide designed to selectively induce apoptosis in senescent cells. It acts as a specific antagonist that disrupts the interaction between the FOXO4 transcription factor and p53, a key regulator of cell survival and apoptosis. By blocking this interaction, FOXO4‑DRI promotes the elimination of senescent cells and has been shown to mitigate age‑related tissue dysfunction and restore tissue homeostasis in preclinical models.

Mechanism of Action
FOXO4‑DRI competitively inhibits the binding of endogenous FOXO4 to p53. This disruption leads to the activation of the p53/BCL‑2/Caspase‑3 signaling pathway, triggering apoptosis specifically in senescent cells while sparing healthy cells. The D‑retro‑inverso configuration (all D‑amino acids) provides enhanced stability and resistance to enzymatic degradation compared to L‑peptides.

Key Benefits

• Selective senolytic activity – targets and eliminates senescent cells.

• Restores tissue homeostasis and improves organ function.

• Alleviates age‑related testosterone secretion insufficiency.

• Reverses effects of chemotoxicity and aging in animal models.

• High stability due to D‑amino acid backbone.

• Cell‑penetrating – readily enters cells to exert its effect.

Applications

• Aging research: Studies on senescence, lifespan extension, and age‑related diseases.

• Regenerative medicine: Investigating clearance of senescent cells for tissue repair.

• Oncology: Exploring senolytic strategies to reduce therapy‑induced senescence.

• Metabolic disorders: Research on senescence in adipose tissue and metabolic dysfunction.

• Neurodegeneration: Potential applications in age‑related cognitive decline.

Recommended Use
For research use only; not for human therapeutic use. Typical in vitro concentrations range from 10–50 μM. Reconstitute in sterile water or suitable buffer as required. Dosage and administration routes should be determined based on specific study protocols.

Handling and Storage

• Store lyophilized peptide at –20°C in tightly sealed containers, protected from light and moisture.

• Avoid repeated freeze‑thaw cycles.

• Use appropriate personal protective equipment (gloves, lab coat, safety goggles) when handling.

• Reconstitute immediately before use; discard any unused reconstituted material after 24 hours.

Packaging
Available in 5 mg vials or plastic tubes. Custom packaging upon request.

Quality Assurance
Each batch is tested for purity (by HPLC), peptide content, and identity (by mass spectrometry) to ensure consistent quality.