A synthetic peptide built from part of the FOXO4 protein using D-amino acids in reversed order (D-retro-inverso), designed to interfere with the FOXO4-p53 interaction. Research is limited to cell and mouse studies; no human trials have been reported.
In senescent cells, the FOXO4 protein binds p53 in the nucleus, which researchers proposed keeps those cells from undergoing apoptosis [1]. FOXO4-DRI was designed to compete for that binding; in cell studies it moved p53 out of the nucleus and increased apoptosis selectively in senescent cells [1]. Later cell and mouse studies reported reduced FOXO4-p53 binding and changes in p53 phosphorylation, BAX, BCL2 and cleaved caspase-3 [3][4]. Whether these effects occur in humans has not been studied.
| Study | Model | Reported result | Source |
|---|---|---|---|
| Baar et al. (original description) [1] | Mouse Doxorubicin-exposure model, accelerated-aging (Xpd TTD) mice and naturally aged mice; senescent cell lines | Researchers reported selective apoptosis of senescent cells, plus measured changes in fitness, fur density and kidney function markers | Peer-reviewed Cell 2017 |
| Leydig cell study [2] | Mouse Naturally aged male mice (20-24 months), n=6 per group; H2O2-induced senescent TM3 Leydig cells | Researchers measured Leydig-cell senescence and inflammatory markers (IL-1β, IL-6, p53, p21, p16) and serum hormones; senescent-cell apoptosis rose from about 10% to 27% in vitro. | Peer-reviewed Aging (Albany NY) 2020 |
| Keloid fibroblast study [3] | Cell Fibroblasts and tissue explants from human keloid-scar tissue under pro-senescence conditions | Increased apoptosis, fewer cells in G0/G1, and nuclear exclusion of p53 phosphorylated at serine 15 | Peer-reviewed Commun Biol 2025 |
| Endothelial senescence study [4] | Mouse Naturally aged (17 months) and D-galactose-induced aging mice; oxygen-glucose-deprived human endothelial cells | Lower p21, p16 and γ-H2AX, thinner aortic wall and lower pulse wave velocity; serum ALT, AST, urea and creatinine reported unchanged | Peer-reviewed Front Bioeng Biotechnol 2026 |
Human trials are listed for research context only; outcomes are reported in the linked publications. Animal and lab results do not establish effects in humans.
PureLab supplies FOXO4-DRI for laboratory research. Lot-specific certificates of analysis are posted on the product page as they are issued.
View research-grade FOXO4-DRI