Description
FOXO4-DRI is a synthetic cell-penetrating peptide constructed using D-amino acid retro-inverso (DRI) chemistry applied to the CR3 domain sequence of the FOXO4 forkhead transcription factor. The DRI configuration inverts the amino acid chirality and reverses the sequence direction. As a result, it produces a peptide that mimics the native structure’s binding surface while gaining near-complete resistance to proteolytic degradation. FOXO4-DRI was developed by Baar et al. and characterized in a 2017 Cell paper as a selective senolytic research tool. Selectivity for senescent cells derives from the elevated FOXO4-p53 nuclear complex density that characterizes senescent cell biology and is absent in proliferating cells. It is studied as a specialty research peptide tool for senescent cell biology and senolytic mechanism research in controlled laboratory models.
Chemical Information
- Chemical Name: FOXO4-D-retro-inverso peptide (FOXO4-DRI)
- Also Known As: FOXO4-DRI; FOXO4 CR3 DRI peptide
- Compound Class: Synthetic D-amino acid retro-inverso cell-penetrating peptide
- Target Interaction: FOXO4-p53 protein-protein interaction (CR3 domain / p53 transactivation domain interface)
- Configuration: D-amino acid retro-inverso (DRI) — protease-resistant mirror image of native L-peptide
- Cell Penetration: Yes, enters nucleus without carrier; designed for intranuclear target engagement
- Molecular Weight: approximately 2,000-2,500 Da (varies by exact sequence)
- Production: Solid-phase peptide synthesis (SPPS) using D-amino acids
Applications
- Senescent cell apoptosis research. FOXO4-DRI selectively induces apoptosis in senescent cells through FOXO4-p53 disruption while sparing proliferating cells; used in models studying the mechanistic basis of senescent cell survival and clearance
- FOXO4-p53 protein-protein interaction studies. The FOXO4-p53 nuclear complex is the specific molecular target. FOXO4-DRI is used as a tool for disrupting and characterizing this interaction through co-immunoprecipitation, proximity ligation assay, and functional apoptosis readouts
- Senescence-associated secretory phenotype (SASP) research. Selective clearance of senescent cells in experimental models reduces SASP-driven paracrine signaling; FOXO4-DRI is used in models examining how senescent cell burden affects surrounding tissue cell populations
- Intrinsic apoptosis pathway research. The p53 nuclear exclusion to mitochondrial translocation cascade, BAX activation, and Caspase-3 cleavage sequence initiated by FOXO4-DRI provides a defined model for studying intrinsic apoptosis induction in senescent cell populations
- D-retro-inverso peptide methodology. FOXO4-DRI serves as a reference compound for studying DRI chemistry as a strategy for intracellular protein-protein interaction targeting. Its protease resistance and cell-penetrating properties make it a model system for this peptide engineering approach
- Tissue-specific senescent cell biology. Published models include senescent fibroblasts, endothelial cells, Leydig cells, and lung epithelial cells. FOXO4-DRI is studied across these populations to characterize how FOXO4-p53 interaction dynamics vary by cell type
Storage and Handling
Store as lyophilized powder at -20C for long-term stability, or at 2-8C for short-term use. Protect from heat, moisture, and direct light. The D-amino acid configuration confers significantly greater proteolytic stability than L-peptide equivalents; however, controlled storage conditions remain important for maintaining compound integrity. Reconstitute immediately before use and avoid repeated freeze-thaw cycles.
Compliance Notice
FOXO4-DRI is for laboratory research use only. It is not for human or veterinary use and carries no therapeutic, diagnostic, or clinical indication. This product has not been evaluated by the FDA. By purchasing this product, the buyer confirms that they will follow appropriate institutional safety procedures and use it exclusively for controlled research.
