Emerging Research

FOXO4-DRI

Longevity & Anti-Aging · ['FOXO4-DRI', 'FOXO4 D-Retro-Inverso peptide', 'proxofim']

FOXO4-DRI is a synthetic D-retro-inverso peptide engineered to disrupt the interaction between the transcription factor FOXO4 and p53, studied as a senolytic that selectively targets senescent cells. It is offered strictly for laboratory research.

🔬 Research use only — not for human or veterinary use. K4 Elite does not provide dosing instructions.

Molecular Formula

C228H388N86O64

Molecular Weight

5358 g/mol

PubChem

CID 167312269 ↗

Research Level

Emerging Research

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FOXO4-DRI is a synthetic peptide designed as a D-retro-inverso (DRI) modification of a segment of the FOXO4 transcription factor. The D-retro-inverso design uses D-amino acids in reversed sequence to confer resistance to proteolysis while preserving the interacting surface, which greatly increases stability relative to a natural L-peptide.

It was introduced in a widely cited 2017 study as a proof-of-concept senolytic: a compound that interferes with the FOXO4-p53 interaction to selectively induce apoptosis in senescent cells while sparing normal cells. This mechanism has made it a prominent tool in longevity and cellular-senescence research.

Content here summarizes peer-reviewed literature. FOXO4-DRI is intended for research use only and is not a drug, supplement, or approved therapy.

In senescent cells, FOXO4 is reported to sequester the tumor-suppressor p53 in the nucleus, helping those cells resist apoptosis. FOXO4-DRI is designed to competitively disrupt the FOXO4-p53 interaction, releasing p53 and permitting its translocation to mitochondria, which drives apoptosis preferentially in senescent cells.

Because normal (non-senescent) cells do not depend on this FOXO4-p53 axis in the same way, the peptide is reported to act selectively on senescent cells in the models studied. This is the basis for its classification as a senolytic research tool.

Senolytic proof-of-concept: FOXO4-DRI selectively induced apoptosis in senescent cells and improved tissue markers in aged and progeroid mice (Baar et al., 2017, Cell).
FOXO4-p53 interaction: Studied as a targeted disruptor of the FOXO4-p53 protein-protein interaction.
Tissue function in aging models: Reported effects on renal function, fur density, and fitness in aged mouse models.
Chemotherapy-induced senescence: Examined in models of doxorubicin-induced senescence and toxicity.
Cellular senescence tool: Used broadly as a research reagent to probe senescent-cell biology in vitro.

📋 How published studies were conducted — a research reference summarizing study designs from the literature. This is not usage, dosing, or administration guidance. K4 Elite does not provide dosing instructions; determining any research protocol is the sole responsibility of the qualified researcher.

Reporting only — not guidance. Baar et al. (2017, Cell) introduced FOXO4-DRI and reported that, in cell culture, it selectively induced apoptosis in senescent cells. In naturally aged, fast-aging (XpdTTD), and doxorubicin-treated mice, the authors administered the peptide and reported neutralization of doxorubicin-induced chemotoxicity, restoration of fitness, fur density, and renal function as research endpoints.

This is a description of the original published animal study; the doses used are reported in the paper for scientific context only. It is not a protocol, recommendation, or endorsement of use.

Combinations examined in the research literature. Descriptive only — not a recommendation to combine compounds.

p53Neutral

The peptide acts by freeing p53 from FOXO4; p53 is central to its mechanism.

FOXO4Neutral

Direct target; the peptide disrupts FOXO4's interaction with p53.

Other senolytics (dasatinib+quercetin)Synergistic

Studied within the same senescent-cell-clearance research field; no established combined-use data.

Chemotherapeutics (e.g., doxorubicin)Caution

Studied in models of chemo-induced senescence; interactions require careful research context.

p53-pathway modulatorsCaution

Shared central node with broad cellular effects; combined effects uncharacterized.

Is FOXO4-DRI approved for human use?

No. FOXO4-DRI is a research compound with no regulatory approval. It is intended for laboratory research use only and is not a drug or supplement.

What does 'DRI' mean?

DRI stands for D-retro-inverso: the peptide is built from D-amino acids in reversed sequence, which increases resistance to enzymatic degradation while preserving the interacting surface.

What is a senolytic?

A senolytic is an agent studied for its ability to selectively eliminate senescent cells. FOXO4-DRI is a widely cited senolytic research tool that targets the FOXO4-p53 interaction.

What was the key study?

Baar et al. (2017, Cell) reported that FOXO4-DRI selectively induced apoptosis in senescent cells and improved several tissue markers in aged and chemotherapy-treated mice. These are research findings, not proven human benefits.

Can you provide dosing?

No. This reference provides research context only. Doses from the original mouse study are reported for scientific context, not as human or veterinary dosing guidance.

Disclaimer: This profile summarizes published preclinical and laboratory research for reference only. It is not medical advice and makes no claim of safety or efficacy in humans. Determining any research protocol is the sole responsibility of the qualified researcher. Products are sold strictly for in-vitro research and have not been evaluated by the FDA.