FOXO4-DRI
Also known as: Proxofim, FOXO4 D-Retro-Inverso
A senolytic peptide designed to selectively destroy senescent ('zombie') cells by disrupting the FOXO4-p53 interaction that keeps these damaged cells alive. It is a promising but very early-stage research compound with no human clinical trials.
How it works
Senescent cells are old, damaged cells that refuse to die and instead release inflammatory signals that damage surrounding healthy tissue. FOXO4-DRI works by blocking the interaction between FOXO4 and p53 proteins inside senescent cells. Normally, FOXO4 traps p53 and prevents the cell from self-destructing. When FOXO4-DRI disrupts this, p53 is freed to trigger apoptosis (programmed cell death) specifically in senescent cells, while leaving healthy cells alone.
Common uses
- Senescent cell clearance (research)
- Anti-aging and longevity research
- Age-related tissue restoration (research)
- Vascular aging research
Side effects
- No human safety data exists
- Unknown side effect profile
- Theoretical risk of affecting healthy cells that rely on FOXO4-p53 interactions
- Injection site reactions likely
- Expensive due to D-amino acid synthesis
Key research
- Original 2017 Cell paper showed FOXO4-DRI restored tissue function in aged mice, improving kidney function, fur density, and fitness
- 2021 study showed selective removal of senescent chondrocytes from human cartilage in lab settings
- 2025-2026 studies show FOXO4-DRI improves vascular function by clearing senescent endothelial cells via p53/BCL-2/Caspase-3 pathway
- Cleara Biotech was formed to commercialize FOXO4-p53 research but remains in preclinical stage
Safety notes
- Zero human clinical trials registered as of April 2026
- Still considered stuck in early development
- D-retro-inverso design makes it resistant to breakdown but also harder and more expensive to manufacture
- Not appropriate for self-experimentation due to complete lack of human safety data
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