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FOXO4-DRI
FOXO4-DRI is a D-retro-inverso senolytic peptide that disrupts the FOXO4-p53 nuclear interaction to selectively induce apoptosis in senescent cells.
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Research peptides at >99% HPLC-verified purity, third-party tested by Janoshik Analytical & Freedom Diagnostics, with Certificates of Analysis published per released batch. Supplied strictly for laboratory research use.
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Research use only - all claims made on this site are for testing and research use only. Purchasers must be 21 years of age or older.
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FOXO4-DRI
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What It's Researched For
In plain terms, FOXO4-DRI is studied mainly as an anti-ageing compound that clears worn-out cells. Here is what that looks like across the research.
Clearing worn-out cells
Lab-dish studies explore how it removes aged senescent cells while leaving healthy cells alone.
Ageing tissue research
Animal studies look at refreshing aged tissue, such as the kidney, by clearing these damaging cells.
Blood-vessel ageing
Preclinical research examines markers of artery ageing and vessel function in naturally aged mice.
Hormone & testis ageing
Animal research explores easing age-related testosterone decline by clearing aged cells in the testes.
Longevity benchmark
Widely used as a reference compound in laboratory senescent-cell and longevity research.
Overview
In short: FOXO4-DRI (Proxofim) is a senolytic peptide that selectively eliminates senescent "zombie" cells by disrupting the FOXO4-p53 interaction - one of the most-cited discoveries in modern aging research.
Key research facts
These points summarise lab themes, not human outcomes.
FOXO4-DRI is a short cell-permeable peptide designed to solve one of aging biology's thorniest problems: what to do about senescent cells. As tissues age, some cells enter a state called senescence - they stop dividing but refuse to die, and they pump out a damaging cocktail of inflammatory signals (the SASP, or senescence-associated secretory phenotype) that ages the tissue around them. These "zombie cells" accumulate over time and contribute to most aging-related pathology.
The insight behind FOXO4-DRI is that senescent cells rely on FOXO4 to sequester p53 in the nucleus, which blocks p53 from triggering its usual apoptotic program. FOXO4-DRI is a short peptide that competitively disrupts that interaction, releasing p53 to move to the mitochondria and kill the senescent cell through the BAX/caspase-3 cascade - without harming healthy dividing cells.
FOXO4-DRI was published in Cell by Baar et al. in 2017 and rapidly became one of the most widely studied senolytic peptides. Supplied here as sterile lyophilised powder for in-vitro and preclinical research.
Mechanism of Action
FOXO4-DRI evicts p53 from the nucleus of senescent cells by displacing the FOXO4 protein that was holding it there, letting p53 trigger the cell's own death program.
Baar et al. (Cell, 2017) published the foundational work showing that FOXO4-DRI restores tissue homeostasis in aged mice by selectively clearing senescent cells. Muntaner et al. (Nature Communications, 2025) characterised the structural basis: FOXO4-DRI binds the disordered p53 transactivation domain (p53TAD2) with higher affinity when p53 is phosphorylated. The all-D retro-inverso topology makes the peptide resistant to proteases, which is essential for a therapeutic intended to reach senescent cells in multiple tissues. Cleara Biotech is developing clinical senolytic candidates based on the FOXO4-p53 mechanism.
Common Questions People Are Asking
What is FOXO4-DRI used for in research?
FOXO4-DRI (Proxofim) is studied as a senolytic tool compound - it is used in cell and animal models to selectively eliminate senescent cells by disrupting the FOXO4-p53 interaction. Researchers use it to probe how clearing "zombie" cells affects aged tissue, vascular function, and inflammation.
What is a "senolytic" and why do they matter?
A senolytic is a compound that selectively kills senescent cells - cells that have stopped dividing but refuse to die and produce a damaging pro-inflammatory secretome. In animal studies, clearing senescent cells extends healthspan and improves tissue function. FOXO4-DRI is one of the best-characterised peptide senolytics, specifically targeting the FOXO4-p53 axis that keeps senescent cells alive.
Why does FOXO4-DRI use D-amino acids?
D-retro-inverso topology (all D-amino acids in reverse order) preserves the side-chain orientation that a protein-protein interaction interface needs to see, while making the peptide resistant to proteases that normally chew up L-peptides. This is especially important for a senolytic, which needs to reach senescent cells in multiple tissues without being degraded in transit.
Does FOXO4-DRI have human clinical trials?
No. All published FOXO4-DRI data is preclinical - cell culture and animal models. The Baar et al. (Cell, 2017) mouse work is the foundational study, and a 2025 Nature Communications paper characterised how the peptide binds the disordered p53 transactivation domain. Clinical senolytic candidates based on the FOXO4-p53 mechanism are in development at Cleara Biotech, but FOXO4-DRI itself remains a research compound, not an approved therapy.
How does FOXO4-DRI compare with dasatinib + quercetin?
They are different senolytic strategies. Dasatinib + quercetin (D+Q) is a small-molecule combination that targets pro-survival pathways broadly across senescent cell types, while FOXO4-DRI is a peptide that specifically disrupts the FOXO4-p53 interaction. FOXO4-DRI is the more targeted, peptide-based approach; both are studied in aging research and neither is established as a human therapy.
Will FOXO4-DRI harm healthy cells?
Baar et al. (Cell, 2017) showed that FOXO4-DRI selectively kills senescent cells while sparing non-senescent dividing cells in vitro. The selectivity comes from the fact that senescent cells specifically rely on FOXO4 to sequester p53, whereas healthy cells do not have the same dependency. That said, senolytic selectivity is an active research area and appropriate caution is warranted.
How should FOXO4-DRI be stored?
Keep the lyophilised powder frozen at −20 °C for long-term storage, or at 2-8 °C during active research use. Reconstitute with sterile PBS or bacteriostatic water. The D-retro-inverso topology gives it unusually good stability in solution compared with L-peptides.
Where can I buy FOXO4-DRI?
Right here - FOXO4-DRI is supplied directly by New-U Research Compounds on this page. Every batch is independently third-party tested to >99% HPLC purity with a batch-linked Certificate of Analysis, supplied as lyophilised research-grade material, and shipped direct from source worldwide in discreet, tracked packaging.
How much does FOXO4-DRI cost?
FOXO4-DRI pricing is shown live on this page, per pack size - 10-vial research packs as standard, with single-vial sample options on selected compounds. Larger vial strengths lower the per-mg cost, every order includes the batch Certificate of Analysis, and shipping is free on orders over $350.
Is FOXO4-DRI third-party tested?
Yes. Every FOXO4-DRI batch is verified by independent laboratories (Janoshik Analytics and Freedom Diagnostics) for identity and purity, with a batch-linked Certificate of Analysis confirming >99% purity by HPLC. Every order ships with its COA, and current batch certificates are published on our COA page.
How do I buy FOXO4-DRI?
Add the FOXO4-DRI pack size you need to your cart and check out: enter your shipping details, then choose your payment method - cryptocurrency or card - on the next step. Every order ships with its batch Certificate of Analysis (COA).
What payment methods can I use to buy FOXO4-DRI?
At checkout you can pay by card or crypto. New-U supports BTC and selected stablecoin and network-asset payments across Ethereum, Solana, TRON, Polygon, Base, BNB Chain and Linea. You choose your method after confirming your order.
How fast is shipping, and do you ship worldwide?
Yes - we ship worldwide in discreet, unmarked, temperature-stable, tracked packaging. Delivery typically takes 6–14 business days, and shipping is free on orders over $350.
Is it legal to buy FOXO4-DRI?
In the United States, FOXO4-DRI is sold strictly for laboratory and research purposes only. It is not approved by the FDA for human consumption and is not sold for that purpose. Regulatory status varies by jurisdiction - buyers are responsible for compliance in their own region.
Research use only - all claims made on this site are for testing and research use only.
Pharmacokinetics
Evidence Tier
Overall: Tier 3: Anecdotal / self-report
FOXO4-DRI evidence is entirely preclinical: in-vitro selective senolysis and a 2025 structural characterisation of p53TAD2 binding (Muntaner et al., Nat Commun), plus single-species (mouse) in-vivo tissue-restoration data from the foundational Baar et al. (Cell, 2017) study. No human clinical trials have been completed (clinical FOXO4–p53 senolytics are in development at Cleara Biotech). It is not approved for any indication and is supplied as unapproved laboratory material.
Tier 2 · Animal
Certificates, databases & peer-reviewed sources
Last reviewed: 16 June 2026 · New-U Research Compounds
Key Characteristics
Specifications
About FOXO4-DRI: Senolytic Peptide Research Guide
Senescent cells are one of the most promising (and frustrating) targets in modern aging biology. They accumulate in aged tissues, they refuse to die, and they pump out a cocktail of pro-inflammatory cytokines (the SASP) that damages neighbouring cells. Clearing these senescent "zombie" cells extends healthspan in mouse studies, which is why a whole class of compounds called senolytics has emerged. FOXO4-DRI (also marketed as Proxofim) is the best-characterised peptide-based member of that class.
The mechanistic story is unusually clean. Baar et al. (Cell, 2017) showed that senescent cells survive because FOXO4 sequesters p53 in the nucleus, preventing it from doing its normal job of triggering apoptosis. FOXO4-DRI competitively disrupts that protein-protein interaction, releasing p53 to translocate to the mitochondria and kill the senescent cell. In that study the peptide neutralised doxorubicin-induced toxicity and, in both fast-aging and naturally aged mice, restored fitness, fur density, and renal function - while young, healthy cells, which do not depend on FOXO4 in the same way, were spared.
New-U Research Compounds supplies FOXO4-DRI as a research-grade lyophilised powder at >95% HPLC purity, verified by independent third-party labs. All material is strictly for in-vitro and preclinical research. FOXO4-DRI has no completed human clinical trials, is not approved for human therapeutic use, and nothing on this page is medical advice. Clinical development of FOXO4-p53 senolytics is ongoing at Cleara Biotech.
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