FOXO4-DRI

FOXO4-DRI is a synthetic peptide designed to interfere with the interaction between FOXO4 and p53, leading to selective apoptosis of senescent cells ('senolysis'). Developed by researchers at Erasmus MC. Limited human data.

PubMed results: 16 · Human studies: 7 · Animal studies: 12

Ranges reflect protocols studied in published research and animal-model extrapolation. Presented for research purposes only, not a recommendation or instruction for human use.

Doses studied in published research. Information presented for research purposes only, not a recommendation for human use.

• Intraperitoneal — standard range 5 mg/kg, About 3 times per week (intermittent). Baar et al. (2017) and follow-on mouse studies used ~5 mg/kg IP on an intermittent multi-week schedule. Ranges from animal research; no established human protocol.
• Subcutaneous — standard range No established dosing, Not established. Human SC research dosing is not established in peer-reviewed trials; only preclinical IP regimens are published.

Not established in humans (theoretical confidence)

D-retro-inverso FOXO4 peptide engineered for protease resistance; no published human PK. Preclinical work used intermittent intraperitoneal dosing in mice without reporting a formal plasma half-life.

• Selective senescent cell clearance (senolysis) research (Strong preclinical): FOXO4-DRI is designed to disrupt FOXO4–p53 interaction, and animal studies demonstrated selective apoptosis of senescent cells (senolysis) with associated improvements in tissue function markers in aged models
• Age-related functional endpoints in animal models (Strong preclinical): Preclinical research at Erasmus MC and related programs reported restoration of fitness-related and organ-function endpoints after senescent cell clearance in experimental aging models
• p53 pathway modulation in senescent cells (Strong preclinical): Mechanistic studies indicate FOXO4-DRI interferes with FOXO4-mediated nuclear sequestration of p53 in senescent cells, allowing p53-dependent apoptosis pathways to proceed preferentially in those cells

• No documented human side-effect profile in published literature — Mild, Not established. Human clinical safety data for FOXO4-DRI remain essentially absent; adverse effects are not established beyond preclinical observations
• Transient inflammatory or clearance-related responses (theoretical) — Moderate, Not established. Senolytic mechanisms that clear large numbers of senescent cells raise theoretical concern for transient inflammatory or tissue-remodeling responses; this is largely inferred from senolytic research class effects rather than FOXO4-DRI-specific human data

• Active cancer or uncontrolled proliferative disease (Theoretical / Preclinical): Modulation of p53-related pathways and selective cell death programs raise theoretical concerns in oncologic contexts where p53 biology is complex and incompletely predictable
• Insufficient human safety data for clinical use (Theoretical / Preclinical): With primarily preclinical evidence and no established human safety dataset, research frameworks treat FOXO4-DRI as experimental with undefined clinical contraindications

Lyophilized (powder): Frozen (-20°C), Up to 24 months. Light sensitive: yes, store dark

Reconstituted (solution): Refrigerated (2-8°C), 4-6 weeks. Solvent: Bacteriostatic water