FOXO4-DRI

Research Overview

FOXO4-DRI is constructed using D-amino acids arranged in a reversed peptide sequence relative to the native FOXO4 interacting domain, a strategy that confers protease resistance while preserving the native-like tertiary fold required for competitive protein–protein interaction disruption. In senescent cells, upregulated FOXO4–p53 nuclear interaction is a survival mechanism that suppresses p53-mediated apoptosis, allowing senescent cells to persist and accumulate in aged tissues. Preclinical in vitro and in vivo studies have examined FOX-04's capacity to disrupt this interaction, triggering selective apoptosis (senolysis) in senescent cells while sparing proliferating cell populations. Supplied exclusively for laboratory and research use.

Cellular senescence — the irreversible cell-cycle arrest programme triggered by DNA damage, telomere dysfunction, or oncogenic stress — is characterised by the senescence-associated secretory phenotype (SASP), a pro-inflammatory secretome that drives paracrine senescence and chronic tissue inflammation. Senescent cells leverage elevated FOXO4-p53 interaction to maintain nuclear p53 in a transcriptionally active but anti-apoptotic configuration, evading cell death. FOXO4-DRI competitively displaces FOXO4 from p53, releasing p53 to the cytoplasm where it can activate mitochondrial apoptotic signalling. Mouse model studies have used FOX-04 to study the phenotypic consequences of targeted senescent cell clearance on tissue regeneration, physical function parameters, and longevity markers in aged animals. All outcomes referenced pertain to preclinical models and do not constitute evidence of clinical efficacy or safety in humans.