FOXO4 10mg

FOXO4-DRI is a D-retro-inverso (DRI) peptide designed to selectively induce apoptosis in senescent cells — making it a senolytic agent. It was developed by Peter de Keizer and colleagues at Erasmus University Medical Center and published in Cell in 2017. The 'D-retro-inverso' design uses D-amino acids assembled in reverse order, creating a peptide that mimics the binding surface of the natural L-peptide but is resistant to proteolytic degradation. In senescent cells, the transcription factor FOXO4 binds to and sequesters p53, preventing p53 from activating its pro-apoptotic program. This FOXO4-p53 interaction is critical for senescent cell survival — without it, p53 would trigger apoptosis and eliminate the senescent cell. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, disrupting the FOXO4-p53 complex and freeing p53 to relocate to the mitochondria and initiate apoptosis. Importantly, FOXO4-DRI shows selectivity for senescent cells over normal cells because the FOXO4-p53 survival pathway is specifically upregulated in senescence. In normal cells, where FOXO4-p53 interaction is minimal, the peptide has little effect. De Keizer et al. demonstrated that FOXO4-DRI treatment restored fitness, fur density, and renal function in both naturally aged and fast-aging (XpdTTD/TTD) mice.

FOXO4-DRI is a D-retro-inverso (DRI) peptide designed to selectively induce apoptosis in senescent cells — making it a senolytic agent. It was developed by Peter de Keizer and colleagues at Erasmus University Medical Center and published in Cell in 2017. The 'D-retro-inverso' design uses D-amino acids assembled in reverse order, creating a peptide that mimics the binding surface of the natural L-peptide but is resistant to proteolytic degradation. In senescent cells, the transcription factor FOXO4 binds to and sequesters p53, preventing p53 from activating its pro-apoptotic program. This FOXO4-p53 interaction is critical for senescent cell survival — without it, p53 would trigger apoptosis and eliminate the senescent cell. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, disrupting the FOXO4-p53 complex and freeing p53 to relocate to the mitochondria and initiate apoptosis. Importantly, FOXO4-DRI shows selectivity for senescent cells over normal cells because the FOXO4-p53 survival pathway is specifically upregulated in senescence. In normal cells, where FOXO4-p53 interaction is minimal, the peptide has little effect. De Keizer et al. demonstrated that FOXO4-DRI treatment restored fitness, fur density, and renal function in both naturally aged and fast-aging (XpdTTD/TTD) mice.

Mouse studies used 5 mg/kg IP administered three times per week for several weeks. In vitro senescent cell clearance was demonstrated at low micromolar concentrations.

Store lyophilized (freeze-dried) powder at -20°C to 4°C in a dry environment protected from light. Unreconstituted peptide is stable for extended periods when stored properly.

Once reconstituted with bacteriostatic water or an appropriate solvent, store at 2-8°C and use within the timeframe specified on the Certificate of Analysis. Avoid repeated freeze-thaw cycles.

A Certificate of Analysis documenting purity, identity, and recommended storage conditions is included with every order.