A senolytic is an agent that selectively clears senescent (aged, non-dividing but persistent) cells; FOXO4-DRI is studied as one such peptide.

How does FOXO4-DRI target only old cells?

Senescent cells rely on a FOXO4-p53 interaction to avoid apoptosis; the peptide disrupts that bond, freeing p53 to trigger cell death in those cells while largely sparing healthy ones.

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Longevity & Anti-aging

Preclinical

FOXO4-DRI (Proxofim)

Also known as: FOXO4-DRI, FOX04-DRI, Proxofim

FOXO4-DRI is a synthetic senolytic peptide studied for selectively clearing senescent cells to counter age-related tissue decline.

Mechanism of Action

FOXO4-DRI is a retro-inverso (D-amino-acid) peptide designed to interfere with the interaction between the FOXO4 transcription factor and p53 within senescent cells. In senescent cells FOXO4 sequesters p53 in the nucleus to keep these cells alive despite damage; by competitively disrupting this FOXO4-p53 binding, the peptide releases p53, which relocates to mitochondria and triggers apoptosis. Because senescent cells are uniquely dependent on this interaction for survival, the peptide acts as a senolytic, selectively eliminating them while sparing healthy cells.

Half-life: Short peptide half-life; D-amino-acid design improves protease resistance
Administration Routes: subcutaneous, intravenous
Research Status: Preclinical