FOXO4-DRI

Overview

FOXO4-DRI is a D-retro-inverso peptide designed to interfere with the FOXO4/p53 interaction that keeps senescent cells alive. By disrupting this interaction, FOXO4-DRI selectively triggers apoptosis in senescent cells while leaving healthy cells unaffected. This makes it a targeted senolytic agent.

Mechanism of Action

Senescent cells avoid apoptosis by sequestering p53 in complex with FOXO4 within PML nuclear bodies. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, releasing p53 to the cytoplasm where it activates the mitochondrial apoptotic pathway. Because only senescent cells rely on FOXO4-mediated p53 sequestration for survival, the peptide selectively eliminates senescent cells (senolysis).

Research Context

Published research in aging mice demonstrated that FOXO4-DRI treatment improved fitness, fur density, and renal function by clearing senescent cells. The D-retro-inverso design confers protease resistance, extending the biological half-life of the peptide.

Key Research Areas

Considerations for Researchers

The D-amino acid composition makes it resistant to enzymatic degradation but also means it cannot be detected by standard L-amino acid peptide assays. Verify using chiral analysis. Store at -20C. Limited vendor base.