FOXO4-DRI
D-retro-inverso peptide that disrupts the FOXO4-p53 interaction and induces apoptosis of senescent cells (senolytic); animal and cell studies only.
60-Second Scientific Briefing
FOXO4-DRI is a modified (D-retro-inverso) peptide designed to remove senescent ("aged") cells, studied as a possible anti-ageing approach. Evidence comes from cell and experimental-animal studies, starting with a 2017 Cell paper; one 2023 study found that removing senescent cells can worsen pulmonary hypertension in animal models. Not approved by the US FDA or any other regulator; it is a research compound.
What is FOXO4-DRI?
Pharmacological Classification & Molecular IdentityFOXO4-DRI is a modified (D-retro-inverso) peptide designed to remove senescent ("aged") cells, studied as a possible anti-ageing approach. [1] Cell, 2017 ↗
Verified Chemical & Regulatory Registry Identifiers
Mechanism of Action & Receptor Targets
Biological Pathway and Target BindingReceptor Selectivity: In senescent cells the protein FOXO4 holds p53 in the nucleus and keeps the cells alive; FOXO4-DRI disrupts this binding so that p53 triggers apoptosis of the senescent cells. [1] Aging (Albany NY), 2020 ↗ [2] Cell, 2017 ↗
Regulatory & FDA Approval Status
Legal and Regulatory ClassificationsNot approved by the US FDA or any other regulator; it is a research compound. [1] Cell, 2017 ↗
FOXO4-DRI is not approved for commercial sale, prescription therapy, or compounded medication distribution. It exists strictly within authorized scientific and clinical research frameworks.
Human Evidence & Clinical Trials
Clinical Study Readouts and Evidence SynthesesNo human clinical trial has been published. Cell 2017: in experimental animals, FOXO4-DRI selectively induced apoptosis of senescent cells and restored tissue homeostasis after chemotherapy damage and in ageing. Aging 2020: in aged animals it targeted senescent Leydig cells and improved testosterone secretion. Circulation 2023: in animal models, eliminating senescent cells (including with FOXO4-DRI) promoted the development and progression of pulmonary hypertension. [1] Aging (Albany NY), 2020 ↗ [2] Cell, 2017 ↗
Clinical Evidence
No human clinical trial has been published. Cell 2017: in experimental animals, FOXO4-DRI selectively induced apoptosis of senescent cells and restored tissue homeostasis after chemotherapy damage and in ageing. Aging 2020: in aged animals it targeted senescent Leydig cells and improved testosterone secretion. Circulation 2023: in animal models, eliminating senescent cells (including with FOXO4-DRI) promoted the development and progression of pulmonary hypertension.
Safety Profile & Clinical Limitations
Documented Adverse Events and Known UncertaintiesThere are no human safety data. A 2023 animal study found that eliminating senescent cells can promote pulmonary hypertension, showing that removing these cells is not automatically beneficial. [1] Circulation, 2023 ↗
Effects and safety in people, which tissues benefit or are harmed by senescent-cell removal, and the quality of non-pharmaceutical material are unknown. [1] Circulation, 2023 ↗ [2] Cell, 2017 ↗
Dose Approval Status
Commercial Dosing Status and Policy DirectivesNo dose is approved or established for humans, and no human dose-finding study has been published. [1] Aging (Albany NY), 2020 ↗
Under Egypt Peptides medical governance policies, no personal dosages, titration intervals, cycles, stacking recommendations, or self-injection instructions may be provided for unapproved investigational compounds. Clinical study protocols represent controlled experimental research parameters exclusively.
What is Known vs. What is Unknown
Evidence Comparison and Clinical Evidence Boundaries✓ Confirmed Scientific Evidence
- FOXO4-DRI is a modified (D-retro-inverso) peptide designed to remove senescent ("aged") cells, studied as a possible anti-ageing approach.
- Targets & Selectivity: In senescent cells the protein FOXO4 holds p53 in the nucleus and keeps the cells alive; FOXO4-DRI disrupts this binding so that p53 triggers apoptosis of the senescent cells.
- No human clinical trial has been published. Cell 2017: in experimental animals, FOXO4-DRI selectively induced apoptosis of senescent cells and restored tissue homeostasis after chemotherapy damage and in ageing. Aging 2020: in aged animals it targeted senescent Leydig cells and improved testosterone secretion. Circulation 2023: in animal models, eliminating senescent cells (including with FOXO4-DRI) promoted the development and progression of pulmonary hypertension.
- Safety considerations: There are no human safety data. A 2023 animal study found that eliminating senescent cells can promote pulmonary hypertension, showing that removing these cells is not automatically beneficial.
? Unknown / Under Ongoing Investigation
- Effects and safety in people, which tissues benefit or are harmed by senescent-cell removal, and the quality of non-pharmaceutical material are unknown.
Verified Questions & Answers
10 Verified scientific answers with permanent anchor keysFOXO4-DRI is a modified (D-retro-inverso) peptide designed to remove senescent ("aged") cells, studied as a possible anti-ageing approach.
In senescent cells the protein FOXO4 holds p53 in the nucleus and keeps the cells alive; FOXO4-DRI disrupts this binding so that p53 triggers apoptosis of the senescent cells.
No. Not approved by the US FDA or any other regulator; it is a research compound.
No human clinical trial has been published. Evidence comes from cell and experimental-animal studies, starting with a 2017 Cell paper; one 2023 study found that removing senescent cells can worsen pulmonary hypertension in animal models.
No human clinical trial has been published. Cell 2017: in experimental animals, FOXO4-DRI selectively induced apoptosis of senescent cells and restored tissue homeostasis after chemotherapy damage and in ageing. Aging 2020: in aged animals it targeted senescent Leydig cells and improved testosterone secretion. Circulation 2023: in animal models, eliminating senescent cells (including with FOXO4-DRI) promoted the development and progression of pulmonary hypertension.
There are no human safety data. A 2023 animal study found that eliminating senescent cells can promote pulmonary hypertension, showing that removing these cells is not automatically beneficial.
- Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression (Circulation, 2023-02-21)
Effects and safety in people, which tissues benefit or are harmed by senescent-cell removal, and the quality of non-pharmaceutical material are unknown.
No dose is approved or established for humans, and no human dose-finding study has been published.
- FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice (Aging (Albany NY), 2020-01-20)
There is no approved product label, so no official storage instructions exist.
It is not named individually on the 2026 WADA Prohibited List. Under section S0 (non-approved substances), any pharmacological substance without a current approval by a government health authority for human therapeutic use is prohibited at all times. Athletes should confirm with their national anti-doping organisation.
- WADA Prohibited List (World Anti-Doping Agency)
Egypt Peptides publishes reviewed scientific reference monographs for documentation and research. The site does not give individual medical advice, preparation or injection instructions, combination protocols or off-label use instructions. Decisions about any medicine belong to the treating physician.
Authoritative Sources & Literature Registry
Regulatory dossiers, clinical trial registries, and published studiesEliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression ↗
https://pubmed.ncbi.nlm.nih.gov/36515093/
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice ↗
https://pubmed.ncbi.nlm.nih.gov/31959736/
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging ↗
https://pubmed.ncbi.nlm.nih.gov/28340339/