FOXO4-DRI Key Research Facts Full name: FOXO4 D-Retro-Inverso peptide (FOXO4-DRI) Classification: Cell-penetrating senolytic peptide FOXO4/p53 protein-protein interaction inhibitor Design: D-retro-inverso isoform of FOXO4s p53-binding domain reversed sequence with all D-amino acids Binding target: p53 transactivation domain 2 (TAD2) displaces FOXO4 from the FOXO4-p53 complex Mechanism: FOXO4-DRI binds p53 TAD2 p53 nuclear exclusion p53 mitochondrial translocation BAX activation caspase-3 cleavage senescent cell-selective apoptosis Selectivity basis: FOXO4 is upregulated in senescent cells but expressed at low levels in most non-senescent adult cells selectivity is mechanistically conferred D-amino acid advantage: Proteolytic stability resistant to intracellular peptidases that would rapidly degrade equivalent L-amino acid sequences Structural characterisation: NMR structural models of FOXO4-DRI/p53TAD2 complex resolved (Nature Communications, 2025) confirms disordered-to-ordered transition upon binding Research cell types studied: IMR90 fibroblasts, TM3 Leydig cells, endothelial cells, chondrocytes, keloid fibroblasts, HCT116 cancer cells In vitro working concentration: 25 M used in multiple published studies for senescent cell apoptosis induction What Does FOXO4-DRI Do in Research
These treatments have been widely studied for metabolic health and weight management
Opt for Small, Frequent, Dry, and Bland Meals: Instead of large meals, which can overwhelm your slower digestive system, choose smaller portions more often
Su sntesis tiene lugar principalmente en el hgado y los riones, aunque su funcin principal se desarrolla en tejidos que requieren grandes cantidades de energa, como el corazn, el cerebro y los msculos
Heart rate and blood pressure assessment Blood pressure and electrocardiogram (ECG) were recorded in anaesthetized, lean mice
While GLP-1RAs demonstrate immunomodulatory potential relevant to SS pathogenesis through their effects on key immune cell populations, direct experimental evidence characterizing their impact on SS-specific immune dysregulation remains strikingly limited
