FOXO4-DRI Research Peptide

FOXO4-DRI is a synthetic research peptide designed to block the interaction between the proteins FOXO4 and p53 inside senescent cells. It was first described in 2017 and is used in laboratory research on cellular senescence, in cell culture and in rodent models of chemotherapy damage, ageing and fibrosis.

DRI stands for D-retro-inverso. The peptide uses D-amino acids, the mirror-image forms of the amino acids found in natural proteins, and lists them in reverse order. The result has side chains arranged much like the natural FOXO4 segment, but a backbone that protein-digesting enzymes recognise poorly, so it lasts longer in biological systems.

A senescent cell has permanently stopped dividing, usually after damage to its DNA, shortened telomeres or other stress, but stays alive and metabolically active. Senescent cells release a mix of inflammatory and tissue-remodelling signals, and they build up with age and after treatments such as chemotherapy, which is why researchers study ways to remove them.

p53 is a protein that decides whether a damaged cell repairs itself, stops dividing or dies. The 2017 study found that in senescent cells, FOXO4 binds p53 in the nucleus and keeps it from triggering cell death. Breaking that bond with FOXO4-DRI released p53 and allowed senescent cells to undergo apoptosis, the cell’s built-in self-destruct process.

At around 5,358 daltons, FOXO4-DRI is several times heavier than short peptides such as Epitalon. It needs a long enough FOXO4-like section to compete for p53 binding, plus a positively charged cell-penetrating section that carries it across cell membranes. The 2025 structural study found that both parts contribute to how it binds.

Most early senolytic compounds were small drug-like molecules that act on survival pathways such as BCL-2 family proteins. FOXO4-DRI is instead a peptide aimed at one protein–protein interaction, FOXO4 with p53. That gives researchers a different tool for asking which survival mechanism senescent cells depend on in a particular tissue or model.

No. Thymalin is a thymus-derived bioregulator studied in immune research, and peptides such as SS-31 target mitochondria. FOXO4-DRI is unusual in being designed to make one specific type of cell, the senescent cell, die, rather than to support or protect cells.

The study reported that FOXO4-DRI caused selective apoptosis of senescent cells in culture, counteracted doxorubicin-induced damage in mice, and improved fur density, fitness and kidney function measures in fast-ageing and naturally aged mice. These are rodent findings from a single research group and have not been tested as such in people.

Yes. A 2021 study on human chondrocytes found that it removed senescent cells but did not improve cartilage formation. A 2023 study in mouse models of pulmonary hypertension found that senolytic interventions including FOXO4-DRI worsened lung blood-vessel pressure measurements and caused loss of endothelial cells. Results clearly depend on the tissue and model.

Leydig cells produce testosterone in the testis. In a 2020 study, FOXO4-DRI selectively cleared senescent Leydig cells in culture and improved the testicular environment in aged mice, and a 2024 study reported improved spermatogenesis in aged mice, linked to reduced inflammatory secretion from senescent Leydig cells.

A 2025 study using nuclear magnetic resonance showed that FOXO4 and FOXO4-DRI both bind the disordered transactivation domain of p53, a flexible region rather than a fixed pocket. It also found that the cell-penetrating section is not just a carrier but takes part in binding, which matters for anyone designing modified versions.

FOXO4-DRI is not a controlled drug under the Misuse of Drugs Act 1971, and it is not a licensed medicine in the UK. It is sold in the UK as a research compound for laboratory use only, which is how Crown Peptides supplies it. This is general information, not legal advice.

FOXO4-DRI is coming soon to Crown Peptides in 10mg vials, available singly or in packs of 3, 5 or 10 with a saving on every vial. Orders ship from the UK, and every batch is independently tested, with its Certificate of Analysis published on this page once stock arrives.

Because FOXO4-DRI is a large peptide of about 5,358 daltons, 10mg is roughly 1.9 micromoles, far fewer molecules per milligram than a short peptide gives. Cell studies typically work in the micromolar range, so one vial covers a moderate amount of in vitro work, and the 5 and 10-vial packs keep a longer project on a single batch.

Keep the unreconstituted powder at -20°C ± 5°C, dry and away from light. Long, highly charged peptides can stick to surfaces and absorb moisture, so vials are best kept sealed until use and brought to room temperature before opening. Prepared solutions should follow storage conditions validated for your study design, and each batch’s Certificate of Analysis documents the material as dispatched.