FOXO4-DRI
FOXO4 D-retro-inverso peptide
FOXO4-DRI is an experimental senolytic peptide designed to kill senescent cells by disrupting the FOXO4–p53 interaction that keeps them alive.
Regulatory status: Not a medicine. It has never been tested in a human trial, is not approved anywhere, and exists only as a research compound.
Default vial
10 mg
Default mix
2 mL
Reported range
No published human dose
Draw (U-100)
100 u
A senolytic studied only in cells and mice. No human trial has ever been run, so no dose is established. Published work also includes a finding that clearing senescent cells made pulmonary hypertension worse in mice — the effect is not uniformly beneficial.
Where these numbers come from
No published study reports a dose for this compound in people. The figures here exist only so the calculator can run — they are not a recommendation. Every FOXO4-DRI study is in cells or mice; no human trial exists.
- Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression, Circulation 2023
- FOXO4-DRI alleviates age-related testosterone secretion insufficiency in aged mice, Aging 2020
- Senolytic peptide FOXO4-DRI selectively removes senescent cells from expanded human chondrocytes, Front Bioeng Biotechnol 2021
Reviewed October 2026
What it is
- A D-retro-inverso peptide: the sequence is built from mirror-image amino acids in reverse order, which makes it far more resistant to breakdown than the natural sequence.
- Derived from the part of FOXO4 that binds p53.
- Studied by injection in mice; no human route or schedule has been established.
- A research compound, not a therapy.
How it is described to act
- 1
In mouse studies it is given by injection, typically in repeated cycles rather than continuously.
- 2
Reported to enter cells broadly rather than targeting one tissue.
- 3
Proposed to block FOXO4 from holding p53 in the nucleus of a senescent cell; researchers report p53 is then excluded from the nucleus and the cell undergoes apoptosis.
- 4
In aged mice this was associated with changes researchers attributed to the loss of senescent cells.
What the research has looked at
Animal work
- In naturally aged mice, researchers reported that FOXO4-DRI targeted senescent Leydig cells and was associated with improved age-related testosterone secretion (Aging, 2020).
- In a rat model of Huntington-like injury and other rodent work, related senolytic approaches have been studied, but FOXO4-DRI itself has been tested in a small number of models only.
Cell studies
- In expanded human chondrocytes, investigators reported FOXO4-DRI selectively removed senescent cells in vitro (Front Bioeng Biotechnol, 2021).
- A 2025 structural study in Nature Communications described the disordered p53 transactivation domain as the target of both FOXO4 and FOXO4-DRI.
Where clearing senescent cells made things worse
- A 2023 Circulation study reported that eliminating senescent cells — by several methods including FOXO4-DRI — promoted the development and progression of pulmonary hypertension in mice.
- That finding matters: senescent cells are not simply damage to be removed, and the consequences of clearing them appear to depend on the tissue and the disease.
Strength of evidence: Preclinical evidence only
Everything published is cell or animal work. No human has been given this compound in a published study, so nothing is known about its effects, dose or safety in people.
What is published comes from cell and animal studies. Findings in those models frequently do not carry over to people.
Reported cautions and unknowns
- There is no human safety data of any kind.
- Published animal work includes a result in the opposite direction to the usual claim: clearing senescent cells worsened pulmonary hypertension in mice.
- A compound designed to trigger apoptosis is, by design, capable of killing cells that were not the intended target. The selectivity reported in cell studies has not been demonstrated in a person.
References
- 1.Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression, Circulation (2023)
- 2.FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice, Aging (2020)
- 3.Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes, Front Bioeng Biotechnol (2021)
- 4.The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI, Nat Commun (2025)
Handling this vial
- Lyophilized vials are generally stored at 2–8 °C and kept out of light; once reconstituted with bacteriostatic water they are refrigerated and commonly discarded after 28 days.
- Mix by aiming water down the vial wall and rolling gently — do not shake — and never re-freeze a reconstituted vial.
- Pep-Tidy cannot verify what is in your vial. Ask your supplier for a current Certificate of Analysis (HPLC/MS).
FOXO4-DRI questions people ask
How do you reconstitute FOXO4-DRI?
A common starting point for a 10 mg vial of FOXO4-DRI is 2 mL of bacteriostatic water, which gives 5 mg per mL. Aim the water down the inside wall of the vial, let it dissolve on its own, and roll gently instead of shaking. Pep-Tidy's reconstitution calculator will recalculate the numbers for any other vial size or water volume you use.
How many units of FOXO4-DRI is one dose?
At 5 mg per mL, that works out to about 100 units on a U-100 insulin syringe for a 5000 mcg dose. Change the vial size, water volume, or target dose in the calculator and the syringe reading updates with it. This is arithmetic, not a dosing recommendation.
What dosing schedule is reported for FOXO4-DRI?
Published and community sources describe No published human dose, subcutaneous, every 3 days, typically run 2 weeks on and 4 weeks off. These figures describe what has been reported, not what anyone should take — talk to a licensed clinician first.
How should FOXO4-DRI be stored?
Lyophilized FOXO4-DRI vials are generally kept at 2–8 °C and out of light. Once reconstituted with bacteriostatic water they are refrigerated and commonly discarded after about 28 days. Never re-freeze a reconstituted vial and never shake it.
Read this before you act on anything above
Everything on this page is a summary of what other people have published — it is not medical advice, not a recommendation, and not a dosing instruction. Reported dose ranges describe what appears in the literature or in community protocols, not what anyone should take. Talk to a licensed clinician before using any peptide.