FOXO4

Product Details

FOXO4-DRI (FOXO4 D-Retro-Inverso) — Research Grade Peptide, ≥95% Purity (HPLC)

Senolytic peptide. FOXO4-p53 interaction disruptor. Lyophilized powder. Lot-specific COA included.

FOXO4-DRI is a 46-amino-acid cell-permeable D-retro-inverso peptide designed to selectively induce apoptosis in senescent cells while sparing healthy cells. It was developed by Peter de Keizer and colleagues at Erasmus University Medical Center in Rotterdam, Netherlands, and first reported in 2017 in Cell as a novel senolytic agent.

The peptide works by disrupting the interaction between the forkhead box O4 (FOXO4) transcription factor and the tumor suppressor protein p53. In senescent cells, FOXO4 binds p53 and sequesters it in PML nuclear bodies, preventing p53 from triggering apoptosis. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, releasing p53 to translocate to mitochondria and activate the intrinsic apoptosis pathway.

A 2025 Nature Communications study solved the solution NMR structural models of the p53 transactivation domain in complex with both the FOXO4 forkhead domain and FOXO4-DRI. The paper found that FOXO4-DRI binds to the disordered p53TAD2 domain and forms a transiently folded complex, and that p53 phosphorylation enhances the affinity for both FOXO4 and FOXO4-DRI. This structural characterization provides the mechanistic basis for developing p53 inhibitors to treat diseases linked to cellular senescence.

Supplied as a sterile-filtered, lyophilized powder for in vitro and preclinical research applications. Each lot is independently verified for purity and identity and ships with a Certificate of Analysis.

Specifications

Note: FOXO4-DRI is synthesized entirely from D-amino acids in reversed sequence. The peptide content specification is ≥60%, with a batch result of 80.50% reported by one supplier, because the molecular weight includes counterions and the peptide content accounts for the actual active material. The HPLC purity percentage and the peptide content figure describe different things. Verify both figures, the D-amino acid composition, and the molecular weight against the Certificate of Analysis supplied with your lot.

Research applications

FOXO4-DRI is used in laboratory settings to investigate:

• Senolytic mechanisms and cellular senescence — selective induction of apoptosis in senescent cells through disruption of the FOXO4-p53 interaction, with structural characterization by NMR

• FOXO4-p53 protein-protein interaction — competitive inhibition of the FOXO4-p53 complex, with FOXO4-DRI binding to p53TAD2 and forming a transiently folded complex

• p53-dependent apoptosis pathways — release of p53 from cytoplasmic sequestration and its translocation to mitochondria to trigger the intrinsic apoptosis cascade

• Age-related tissue dysfunction — clearance of senescent cells in aged mice, with reported restoration of fur density, improved renal function, and extended physical performance

• Senescence-associated secretory phenotype (SASP) — modulation of the inflammatory secretome produced by senescent cells and its contribution to age-related pathologies

• D-retro-inverso peptide pharmacology — the DRI design strategy as a model for enhancing peptide stability and extending biological half-life

• Cancer and senescence research — the structural basis for developing p53 inhibitors to treat diseases linked to cellular senescence

• Analytical method development — LC-MS/MS quantification and reference standard preparation for D-amino acid peptide analysis

Handling and storage

Reconstitute under aseptic conditions using sterile water or an appropriate aqueous buffer. FOXO4-DRI is soluble in water. Aliquot immediately after reconstitution to avoid repeated freeze-thaw cycles. Lyophilized powder is stable for up to 2 years at −20 °C under sealed, desiccated, light-protected conditions. Reconstituted solutions should be stored at 2–8 °C and used within 14–21 days. Do not freeze reconstituted solution.

For laboratory use by qualified personnel only.