FOXO4-DRI is a "senolytic" peptide that, in mouse experiments, selectively removed old, "stuck" cells without affecting healthy ones. It is studied as a way to rejuvenate tissues by clearing out such cells.
D-Ret-D-Leu-R8 analog of the FOXO4-p53 binding domain — a retro-inverso peptide. ~3 kDa.
Targeted senolytic: selectively eliminates senescent cells by disrupting the FOXO4-p53 interaction → apoptosis. In mice: ↑physical function, ↑kidney function, ↑healthier-looking fur, ↑running performance. Senolytic effect without toxicity to normal cells.
Senescent cells retain FOXO4 in the nucleus → this shields p53 from its apoptotic function. FOXO4-DRI disrupts this interaction → p53 migrates to the mitochondria → apoptosis of senescent cells. Normal cells: p53 is in the cytoplasm → no effect.
Studies used 5 mg/kg SC 3 times a week for 1 week; a fixed dose of 5 mg has also been described. Only a "hit-and-run" intermittent regimen was used.
Level C Animal studies. Effects have been shown in animals. Whether they carry over to humans has not been proven.
Mice only. Phase I has not started. Manufacturing is complex. Retro-inverso peptide = non-standard synthesis → risk of contamination. Research only.
Research peptides are laboratory reagents (Research Use Only). They are not medicines and are not intended for use in humans or animals.