FOXO4-DRI is an innovative peptide bioregulator of the senolytic class, developed for the selective elimination of senescent (functionally worn out) cells. It is considered as one of the most promising tools in rejuvenation programs at the cellular level, reducing biological age and restoring tissue homeostasis.
FOXO4-DRI is a synthetic D-retro-inverso peptide designed to disrupt the interaction between FOXO4 and p53. In the research context, the compound is being studied as a senolytic peptide capable of selectively affecting senescent cells. In scientific publications and profile chemical cards, FOXO4-DRI is described as an all-D-enantiomer retro-inverso peptide with a characteristic sequence and research application in models of cellular aging.
General information
| Features | Values |
|---|---|
| The peptide sequence | H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OHl |
| The molecular formula | C228H388N86O64 |
| Molecular weight | 5358 g/mol |
| CAS Number | 2460055-10-9 |
| PubChem CID | 167312269 |
| Synonyms | FOXO4-DRI, FOXO4 D-Retro-Inverso, FOXO4-DRI TFA salt form |
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Product Usage
This product is intended solely for research purposes. All product information provided on this website is intended for educational purposes.
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FOXO4-DRI is a synthetic senolytic peptide developed to disrupt the interaction of FOXO4 with p53 in senescent cells. In key works, it is described as a D-retro-inverso peptide, which, after attaching the TAT sequence, is able to enter the cell and cause apoptosis mainly in senescent cells due to the release of p53 from nuclear confinement. That is why FOXO4-DRI is considered one of the most well-known research molecules in the field of cellular aging, senolysis, tissue remodeling and age-related disorders. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging: Cell
Senolytic action
The main research area of FOXO4-DRI is related to the selective removal of senescent cells. In the original work of Cell, it was shown that interference with the FOXO4-p53 axis leads to loss of viability in senescent cells, whereas non-senescent cells are significantly less affected. Mechanically, this is due to the fact that in senescent cells, FOXO4 promotes nuclear retention of p53 and maintains the state of cell arrest, while FOXO4-DRI disrupts this contact and puts p53 into a pro-apoptotic mode. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging: Cell
Cellular aging and p53
FOXO4-DRI is particularly interesting as a tool for studying the molecular biology of senescence. Later biophysical and modeling work confirmed that the peptide interferes with the interaction of FOXO4 and p53 and can bind to the p53-binding interface with high affinity, which supports the original concept of its action. Therefore, it is correct for the site to describe it not just as an anti-age peptide, but as a research senolytic associated with the regulation of the FOXO4-p53 pathway. Identification of hotspots in synthetic peptide inhibitors of the FOXO4:p53 interaction
Age-related tissue changes
After the first publication, FOXO4-DRI began to be actively studied in models of age-related tissue disorders. Reviews on senolytics indicate that in preclinical studies, removal of senescent cells using FOXO4-DRI was associated with improved tissue homeostasis, physical function, and individual signs of age-related decline in animals. This has supported interest in the peptide as a model for studying tissue rejuvenation, although such data so far relate specifically to the preclinical stage, and not to standard clinical practice.
Fibrosis and remodeling of the extracellular matrix
A separate area of FOXO4-DRI research is related to fibrosis. In a 2023 paper on pulmonary fibrosis, it was reported that FOXO4-DRI affected activated fibroblasts and extracellular matrix, and the authors attributed this to the effect on p53-dependent mechanisms and senescent phenotype of cells. This makes the peptide promising for studying not only aging as such, but also pathological tissue remodeling, where senescent cells accumulate. FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice - PubMed
Skin and scarring
New work has expanded the interest in FOXO4-DRI to the area of skin and pathological scarring. In a 2025 study on keloid models, it was shown that FOXO4-DRI enhanced apoptosis of senescent fibroblasts and was accompanied by nuclear exclusion of phosphorylated p53. These data reinforce the interest in the peptide as a tool for studying stable senescent cell populations in tissues with chronic remodeling. FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation | Communications Biology
Vascular aging
In more recent publications, FOXO4-DRI has also been studied in models of endothelial and vascular aging. In a 2026 paper, the authors attributed its effect to the activation of the p53/BCL-2/Caspase-3 cascade and reported an improvement in vascular function in a preclinical model. These results look promising, but they still belong to the early research stage and require careful interpretation. FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway - PMC
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