What is FOXO4-DRI?
FOXO4-DRI is a synthetic 46-amino-acid peptide built entirely from D-amino acids in retro-inverso order. It combines a fragment of the forkhead box O4 (FOXO4) protein with an HIV-TAT cell-penetrating sequence, allowing it to enter cells and compete with endogenous FOXO4 for binding to the tumour suppressor p53.
In senescent cells FOXO4 holds p53 in the nucleus and keeps the cell alive despite its damaged state. FOXO4-DRI was designed to break that interaction so p53 can move to the mitochondria and trigger apoptosis selectively in senescent cells. Published preclinical work in mouse models of accelerated and natural ageing reported clearance of senescent cells and improvements in tissue markers, which established FOXO4-DRI as one of the best-known peptide senolytics.
GenoPept supplies FOXO4-DRI in the UK in 2mg and 10mg lyophilised vials, each batch verified at ≥99% purity with a Certificate of Analysis, strictly for in-vitro laboratory research.
FOXO4-DRI research applications
FOXO4-DRI is studied in cellular senescence, ageing biology and related disease models. The applications below summarise published preclinical and cell-culture research; they are not claims about effects in people.
Senolytic screening in cell culture
FOXO4-DRI is used as a reference senolytic when testing whether removal of p16- or p21-positive senescent cells alters inflammatory secretion (the SASP) in fibroblast, endothelial and epithelial cultures.
Ageing and progeroid mouse models
The original research investigated FOXO4-DRI in XpdTTD/TTD progeroid mice and naturally aged mice, reporting effects on fur density, renal function and physical activity that researchers continue to replicate and extend.
Chemotherapy-induced senescence
Doxorubicin and other chemotherapeutics induce senescence in healthy tissue. FOXO4-DRI is studied for its ability to clear these cells in preclinical models of chemotoxicity.
Osteoarthritis and intervertebral disc models
Senescent chondrocytes and disc cells are implicated in joint degeneration, and FOXO4-DRI is investigated in these tissue models as a targeted senolytic.
p53 and FOXO signalling biology
Beyond senolysis, the peptide is a tool for dissecting the FOXO4-p53 axis, DNA-damage responses and mitochondrial apoptosis pathways.
Mechanism of action (preclinical)
FOXO4-DRI enters cells via its TAT-derived cationic sequence. Its forkhead-domain fragment binds p53 with higher affinity than native FOXO4, displacing p53 from the nuclear FOXO4-p53 complex that senescent cells rely on for survival. Freed p53 translocates to mitochondria and initiates intrinsic apoptosis, while non-senescent cells, which lack this dependency, are reported to be comparatively unaffected.
The D-retro-inverso design reverses the sequence and inverts chirality so the side-chain topology of the L-peptide is preserved while the backbone resists proteolytic degradation. This gives the peptide a longer functional lifetime in biological media than an equivalent L-amino-acid sequence.
FOXO4-DRI product specifications
| Specification | Detail |
|---|---|
| Compound | FOXO4-DRI |
| Also known as | FOXO4 D-retro-inverso peptide, FOXO4-DRI peptide, FOXO4 senolytic peptide |
| Sequence / class | 46-amino-acid synthetic D-retro-inverso peptide (FOXO4 forkhead-domain fragment fused to an HIV-TAT cell-penetrating sequence, all D-amino acids) |
| CAS number | 2460055-10-9 |
| Form | Lyophilised (freeze-dried) powder in a sealed sterile glass vial, black cap, lot and expiry on label |
| Available sizes | 2mg, 10mg |
| Purity | ≥99% (HPLC) |
| Verification | Batch HPLC purity and LC-MS identity testing by an independent ISO/IEC 17025 laboratory (Puralytix), with Certificate of Analysis |
| Storage (unopened) | −20 °C long term; 2–8 °C short term; protect from light |
| Intended use | In-vitro laboratory research only. Not for human or veterinary use |
Available sizes
FOXO4-DRI is available from GenoPept in the following vial sizes:
- FOXO4-DRI 2mg vial
- FOXO4-DRI 10mg vial
Laboratories that need larger quantities can order FOXO4-DRI in bulk boxes of 10 vials, which save 20–50% against single-vial pricing. Retail baskets also receive automatic discounts at £300, £500 and £1,000, and delivery is free on UK orders of £200 or more.
Reconstitution, handling and storage (laboratory)
Unopened FOXO4-DRI vials should be stored at −20 °C for long-term storage, or at 2–8 °C for short periods, and protected from light. Allow the vial to reach room temperature before opening to avoid condensation on the lyophilised cake.
To reconstitute for in-vitro work, add bacteriostatic water or another sterile diluent slowly down the inside wall of the vial, then swirl gently until the powder dissolves. Do not shake. The peptide is highly cationic and adsorbs to some plastics, so low-binding tubes are advisable for dilute working solutions. Reconstituted solution should be kept at 2–8 °C and used within the period specified in the laboratory’s own protocol. See our guides on how to reconstitute research peptides and how to store research peptides for step-by-step handling notes.
Quality assurance and Certificate of Analysis
Every batch of FOXO4-DRI sold by GenoPept is tested by an independent third-party laboratory (Puralytix, ISO/IEC 17025 accredited) using HPLC for purity and LC-MS for identity confirmation. Results are published in a batch-specific Certificate of Analysis (COA), and each vial is labelled with its lot number and expiry date so the paperwork can be matched to the product on the bench.
Use the “View Certificate of Analysis” button on this page to open the current FOXO4-DRI COA, or browse the full COA library. Our article on what a Certificate of Analysis shows explains how to read the chromatogram and mass spectrum.
Related research compounds
- Epitalon (Epithalon): a tetrapeptide bioregulator investigated in telomerase and ageing research.
- Humanin: a mitochondrial-derived peptide studied for cytoprotective signalling in ageing models.
- SS-31 (Elamipretide): a mitochondria-targeted tetrapeptide studied in oxidative-stress and ageing research.
- NAD+: the coenzyme whose decline is linked to senescence and DNA-repair capacity.
FOXO4-DRI frequently asked questions
What is FOXO4-DRI used for in research?
FOXO4-DRI is used as a senolytic tool compound in cellular senescence and ageing research. It disrupts the FOXO4-p53 interaction that keeps senescent cells alive, allowing p53-driven apoptosis. Laboratories use it in fibroblast cultures, progeroid and aged mouse models, chemotherapy-induced senescence and joint-tissue models. It is supplied in the UK for in-vitro laboratory research only.
How is FOXO4-DRI supplied and what purity is it?
GenoPept supplies FOXO4-DRI as a lyophilised powder in sealed sterile glass vials of 2mg and 10mg. Every batch is tested at ≥99% purity by HPLC with identity confirmed by LC-MS at an independent ISO/IEC 17025 laboratory, and the batch-specific Certificate of Analysis can be viewed from the button on this page or in the COA library.
How should FOXO4-DRI be stored?
Keep unopened FOXO4-DRI vials at −20 °C for long-term storage, or 2–8 °C for short periods, protected from light. After reconstitution keep the solution at 2–8 °C, use low-binding tubes for dilute aliquots, and use within the period set by your laboratory protocol. Avoid repeated freeze-thaw cycles.
Is FOXO4-DRI for human use?
No. FOXO4-DRI sold here is strictly for in-vitro laboratory research. It is not a medicine, has not been approved by any regulator, and is not for human or veterinary use, diagnosis or therapy. This page provides no dosing or usage guidance for people; it describes published preclinical research only.
What does D-retro-inverso mean, and why does it matter?
A D-retro-inverso (DRI) peptide is synthesised from D-amino acids in the reverse order of the native L-sequence. This preserves the spatial arrangement of the side chains, so the peptide can still bind its target, while the unnatural backbone resists proteases. For FOXO4-DRI this design gives a longer active lifetime than the native FOXO4 fragment, which is why it is the form used in senolytic research.
Research use only. FOXO4-DRI is supplied by GenoPept strictly for in-vitro laboratory research. It is not a medicine, is not for human or veterinary use, and is not intended for diagnostic or therapeutic purposes. Read our research use only policy and UK legal guide before ordering.
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