FOXO4
Also known as FOXO4-DRI, FOXO4-D-Retro-Inverso peptide
FOXO4-DRI is a synthetic D-retro-inverso peptide designed to block the interaction between the transcription factor FOXO4 and p53. Researchers study it as a senolytic, an agent that selectively triggers apoptosis in senescent cells.
Preclinical research
Size
1 option- Catalog no.
- F410
- Specification
- 10mg*10vials
- Per kit
- 10 vials
For laboratory research use only. Not for human or animal consumption. Buyers must be 21 or older.
Overview
FOXO4-DRI was reported in 2017 by Peter de Keizer's group at Erasmus University Medical Center in Rotterdam. It is based on the region of FOXO4 that binds p53, built from D-amino acids in reversed order (retro-inverso) to resist breakdown by proteases, and joined to a cationic cell-penetrating sequence. Senescent cells are thought to rely on the FOXO4-p53 interaction in the nucleus to avoid apoptosis. Blocking it releases p53 from the nucleus and leads to apoptosis in those cells. Research to date consists of cell culture, structural, and animal studies, including mouse models of chemotoxicity, accelerated aging, natural aging, and age-related testosterone decline.
Class: Senolytic peptide (FOXO4-p53 interaction inhibitor)
Mechanism of action
How the compound acts, as described in the literature.
FOXO4 is elevated in senescent cells and binds p53 in the nucleus, an interaction associated with stable growth arrest and resistance to apoptosis.
FOXO4-DRI competes with FOXO4 for p53, causing p53 nuclear exclusion and cell-intrinsic (mitochondrial) apoptosis selectively in senescent cells.
NMR structural work showed the peptide binds the disordered p53 transactivation domain 2 (TAD2), and p53 phosphorylation increased its affinity for both FOXO4 and FOXO4-DRI.
The D-retro-inverso design keeps a side-chain arrangement similar to the native sequence while making the peptide resistant to protease degradation.
Published research
Selected studies, each linked to its PubMed record. Summaries describe what the studies reported.
2017
Rodent and in vitro study
PMID 28340339Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.
Baar MP, et al. · Cell
Identified FOXO4 as a factor in senescent cell viability and designed FOXO4-DRI. In mice it countered doxorubicin-induced chemotoxicity and restored fitness, fur density, and renal function in fast-aging XpdTTD/TTD and naturally aged animals.
2020
Rodent and in vitro study
PMID 31959736FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.
Zhang C, et al. · Aging (Albany NY)
In senescent TM3 Leydig cells, FOXO4-DRI caused p53 nuclear exclusion and apoptosis. In naturally aged mice, it improved the testicular microenvironment and reduced the age-related decline in testosterone secretion.
2025
Structural (NMR) study
PMID 40593617The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.
Bourgeois B, et al. · Nat Commun
Solved solution NMR models of the p53 transactivation domain bound to the FOXO4 forkhead domain and to FOXO4-DRI. The peptide bound p53 TAD2 in a transiently folded complex, and p53 phosphorylation increased binding affinity.
Evidence & safety
What the research does not show, and the adverse events and regulatory status it reports.
All evidence is preclinical, from cell culture, structural, and mouse studies; FOXO4-DRI has not been tested in human trials and is not approved. In mouse models of pulmonary hypertension, senolytic interventions including FOXO4-DRI worsened pulmonary hemodynamics and depleted lung endothelial cells. Long-term safety and selectivity in living organisms are not established.
Specifications
All sizes, exactly as catalogued.
| Catalog no. | Product | Specification | Vials per kit |
|---|---|---|---|
| F410 | FOXO4 | 10mg*10vials | 10 |
For laboratory research use only. Not for human or animal consumption. Not intended to diagnose, treat, cure or prevent any disease. Research summaries are provided for educational purposes and do not describe this product’s use.