FOXO4-DRI, commonly shortened as FOXO4 peptide and also named Proxofim, is a synthetic cell-permeable D-retro-inverso modified peptide specifically engineered to disrupt the protein-protein interaction between endogenous FOXO4 transcription factor and p53 protein. FOXO4 belongs to the forkhead box O family of winged-helix transcription factors, which governs a broad spectrum of cellular events including oxidative stress response, cell cycle arrest, DNA damage repair, apoptosis and metabolic homeostasis. Native FOXO4 can bind tightly with p53 inside the nucleus of senescent cells, trapping p53 within the nuclear compartment and preventing p53-mediated apoptotic signaling. This binding protects senescent cells from programmed cell death and allows these dysfunctional cells to persist in tissues, continuously secreting inflammatory factors and driving age-related tissue deterioration.

FOXO4-DRI adopts D-amino acid retro-inverso configuration, a special peptide modification strategy that greatly improves protease resistance compared with natural L-amino acid peptides. This structural design grants the peptide enhanced stability in biological fluids and enables efficient cell penetration. Once delivered into senescent cells, FOXO4-DRI competes with endogenous FOXO4 for p53 binding sites. By breaking FOXO4-p53 complex formation, it triggers nuclear export of p53 and selectively initiates apoptosis in senescent cells, while leaving healthy, non-senescent cells largely unharmed. This selective senescent cell clearance property makes FOXO4-DRI one of the most widely investigated senolytic research molecules in aging biology.

Apart from core senolysis research, FOXO4-DRI is extensively applied in multiple preclinical research directions. It is used to explore senescence-associated secretory phenotype (SASP), tissue fibrosis, degenerative joint disease, muscle wasting and age-related organ functional decline. Researchers also utilize this peptide to investigate senescence’s contribution to metabolic disorders, neuroinflammation and wound healing processes. The D-retro-inverso modification endows the peptide with outstanding resistance to enzymatic degradation, which simplifies experimental handling and extends its effective window in cell and animal model studies.

Our FOXO4-DRI is manufactured via solid-phase peptide synthesis, assembling each D-amino acid residue sequentially. Crude peptide undergoes multiple rounds of reversed-phase preparative HPLC purification to remove truncated sequences, deletion fragments, residual protecting groups and by-products generated during synthesis. Every batch undergoes full quality control workflows, including HPLC purity analysis, ESI mass spectrometry for molecular weight confirmation, moisture detection and visual appearance inspection. Complete COA, HPLC chromatogram and mass spectrum reports can be provided for each shipment to satisfy strict laboratory documentation and audit requirements. The final lyophilization procedure stabilizes the peptide backbone, minimizing degradation risk during international transit and long-term frozen storage. This product is supplied to university laboratories, biotech R&D institutions and geroscience research teams for cell senescence models, senolytic compound screening, SASP pathway exploration, tissue aging, chondrocyte senescence and anti-senescence mechanism studies.