FOXO4-DRI

Third-Party Tested

Independent lab verified

Batch-Specific CoA

Publicly accessible

YPB.255

Reference number

10mg

Lyophilized vial

Origin

FOXO4-DRI was developed by Peter de Keizer and colleagues at Erasmus University Medical Center in Rotterdam. Published in Cell in 2017, it was designed as a D-retro-inverso (DRI) peptide that disrupts the FOXO4-p53 interaction in senescent cells, a protein-protein interaction that maintains senescent cell viability.

Research Lineage

De Keizer et al. demonstrated that FOXO4-DRI selectively induced apoptosis in senescent cells while sparing non-senescent cells in mouse models. The publication generated significant interest in the senolytic research field. It represents one of the first rationally designed peptide-based senolytics, distinct from small molecule approaches like dasatinib/quercetin.

Mechanism of Action

In senescent cells, FOXO4 binds to p53 and sequesters it in PML nuclear bodies, preventing p53-mediated apoptosis. FOXO4-DRI competitively disrupts this interaction by mimicking the FOXO4 binding domain but in a protease-resistant D-amino acid configuration. Freed p53 then activates the intrinsic apoptotic pathway, selectively eliminating the senescent cell.

Structural Notes

D-retro-inverso peptidomimetic. Composed entirely of D-amino acids in reversed sequence, providing protease resistance while maintaining the spatial orientation of side chain interactions. 23-amino-acid peptide.