FOX04-DRI (Proxofim)

FOXO4-DRI (Proxofim) is a D-retro-inverso peptide designed to disrupt binding between the transcription factor FOXO4 and p53. It was introduced in a 2017 study that identified FOXO4 as a factor keeping senescent cells viable; in senescent cells the peptide caused p53 nuclear exclusion and apoptosis. Later studies of the FOXO4-DRI peptide used expanded human chondrocytes and lung fibroblasts, and NMR work mapped its binding to the p53 transactivation domain. Research Market supplies FOXO4-DRI as a lyophilized research reagent, with purity and identity data for each lot reported on its certificate of analysis. It is sold strictly for laboratory research use.

Chemical structure and identification

• Molecular formula: C₂₂₈H₃₈₈N₈₆O₆₄
• Molecular weight: 5358 g/mol
• CAS number: 2460055-10-9
• PubChem CID: 168431240
• Structure: D-retro-inverso peptide made of a FOXO4-derived region and a cationic cell-permeability sequence
• Synonyms: FOXO4 D-Retro-Inverso; FOXO4 peptide
• Form: Lyophilized powder
• Analytical methods: RP-HPLC for purity and mass spectrometry for identity, reported on the batch certificate of analysis

Research applications

• Senescent cell apoptosis: The FOXO4 peptide perturbed FOXO4–p53 binding and selectively caused p53 nuclear exclusion and cell-intrinsic apoptosis in senescent cells; in mice it was studied against doxorubicin-induced chemotoxicity and in fast-aging Xpd^TTD/TTD and naturally aged animals [1]
• p53 binding structure: Solution NMR showed the disordered FOXO4-DRI binding the disordered p53 TAD2 region to form a transiently folded complex, with both the FOXO4-derived region and the cell-permeability peptide contributing and p53 phosphorylation raising affinity [2]
• Expanded human chondrocytes: In human chondrocytes expanded to population doubling level 9, FOXO4-DRI removed more than half of the cells and lowered senescence levels, without improving chondrogenic potential in pellet culture [3]
• Pulmonary fibrosis model: In bleomycin-treated mice, FOXO4-DRI was associated with milder lung pathology and less collagen deposition, and in activated fibroblasts it reset intranuclear p53 distribution and lowered extracellular matrix protein content [4]

Reference citations

1. Baar M.P. et al. (2017). Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell, 169(1):132–147.e16. PMID 28340339 · DOI
2. Bourgeois B. et al. (2025). The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nat Commun, 16(1):5672. PMID 40593617 · DOI
3. Huang Y. et al. (2021). Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes. Front Bioeng Biotechnol, 9:677576. PMID 33996787 · DOI
4. Liu Y. et al. (2023). FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice. Naunyn Schmiedebergs Arch Pharmacol, 396(10):2393–2403. PMID 37074394 · DOI

Compound data from PubChem CID 168431240. Literature summaries describe published preclinical research and are not claims about this product’s effects in humans or animals.