FOXO4-DRI 10 mg

FOXO4-DRI 10 mg research-grade lyophilized peptide powder in a glass vial. FOXO4-DRI is a D-retro-inverso peptide designed to disrupt the interaction between the transcription factor FOXO4 and p53, and is used in experimental models of senescent cells, cellular aging and tissue homeostasis.

Research Overview

FOXO4-DRI is used in research as a tool peptide to probe FOXO4–p53 signaling in senescent cells. By disrupting this interaction, it enables experimental investigation of selective senescent-cell clearance, tissue homeostasis and cellular aging pathways in vitro and in vivo laboratory models.

Primary Research Areas

• FOXO4–p53 interaction & signaling: Experimental studies examining how FOXO4-DRI disrupts FOXO4–p53 binding and alters downstream apoptosis and stress-response pathways in senescent cells [1].
• Senolysis & cellular senescence models: In vitro and in vivo models evaluating selective targeting of senescent cells and effects on senescence markers, SASP factors and tissue microenvironments [1,2].
• Aging & tissue homeostasis research: Laboratory investigations into how modulation of senescent-cell burden impacts tissue regeneration, organ function and age-related decline in controlled experimental systems [1].
• Testosterone in old age: worn-out hormone-producing cells in the testis were pushed into dying, and the age-related shortfall in testosterone eased in naturally aged mice. Human Leydig cells were only looked at down a microscope. No person has been given this peptide [3].
• Sperm quality in old mice: aged mice given the peptide made better sperm and made it more effectively, because the senescent support cells that spoil the environment inside the testis were cleared out. Mice only, and whether any pups were born was not reported [4].
• Stiffening arteries: injected into naturally aged mice and into mice bred to age fast, it reduced ageing changes in the aorta and improved how the vessel worked, by driving worn-out lining cells to self-destruct. No blood pressure reading and no human data [5].
• Raised scars: keloid scars carry an unusual load of worn-out cells that refuse to die. In pieces of human keloid kept alive in the laboratory, and in cells grown from them, the peptide pushed those cells into dying. Laboratory tissue, not a treated patient [6].
• Lung scarring: mice whose lungs were scarred with bleomycin and then treated had fewer senescent cells, less collagen laid down and less distorted lung tissue, roughly matching the licensed drug pirfenidone. One mouse model, and breathing itself was never measured [7].
• Lung blood pressure can worsen: clearing senescent cells is not always helpful. In mice bred to develop pulmonary hypertension this peptide made pressures in the lung circulation worse and stripped out lung vessel lining cells, as a chemical senolytic also did. The finding comes from a lung and heart disease model [8].

References

1. Baar MP, Brandt RMC, Putavet DA, et al. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017;169(1):132-147.e16. PMID 28340339. doi:10.1016/j.cell.2017.02.031
2. Huang Y, He Y, Makarcyzk MJ, et al. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells FromExpanded Human Chondrocytes. Front Bioeng Biotechnol. 2021;9:677576. PMID 33996787. doi:10.3389/fbioe.2021.677576
3. Zhang C, Xie Y, Chen H, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY). 2020;12(2):1272-1284. PMID 31959736. doi:10.18632/aging.102682
4. Li Y, Zhang C, Cheng H, et al. FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells. Exp Gerontol. 2024;195:112522. PMID 39025385. doi:10.1016/j.exger.2024.112522
5. Hu Z, Li F, Hu C, et al. FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway. Front Bioeng Biotechnol. 2025;13:1729166. PMID 41625068. doi:10.3389/fbioe.2025.1729166
6. Kong YX, Li ZS, Liu YB, et al. FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation. Commun Biol. 2025;8(1):299. PMID 39994346. doi:10.1038/s42003-025-07738-0
7. Han X, Yuan T, Zhang J, et al. FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway. J Cell Mol Med. 2022;26(11):3269-3280. PMID 35510614. doi:10.1111/jcmm.17333
8. Born E, Lipskaia L, Breau M, et al. Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression. Circulation. 2023;147(8):650-666. PMID 36515093. doi:10.1161/CIRCULATIONAHA.122.058794