FOXO4-DRI
preclinicalAlso known as: FOXO4-D-Retro-Inverso, Proxofim
**Mechanism of Action** FOXO4-DRI (Proxofim) is a D-retro-inverso peptide designed to selectively target senescent cells. It disrupts the interaction between FOXO4 and p53, a key survival pathway in senescent cells. By blocking FOXO4-p53 binding, the peptide releases p53 to translocate to the mitochondria, where it triggers intrinsic apoptosis. This mechanism spares non-senescent cells, as they lack the FOXO4-p53 dependency that maintains senescent cell viability. **Key Research Findings** Preclinical studies (17 PubMed references) demonstrate that FOXO4-DRI reduces senescence markers (e.g., SA-β-gal, p21) and clears senescent cells in aged mouse models, improving renal function, hair regrowth, and physical performance. In chemotherapy-induced senescence models, it alleviates frailty and tissue damage without overt toxicity. However, efficacy varies by tissue type, and long-term safety data remain limited. No human trials have been conducted. **Clinical Relevance** FOXO4-DRI represents a promising senolytic candidate for age-related diseases and chemotherapy side effects. Its selective apoptosis mechanism may avoid off-target effects seen with other senolytics. However, clinical translation is hindered by peptide stability, delivery challenges, and the need for rigorous safety profiling in humans. Current evidence is confined to preclinical models. For research purposes only — not medical advice.
Key data
C228H388N86O64Research & studies
Keloids have increased pro-inflammatory and mesenchymal fibroblast subpopulations, senescent fibroblasts, and senescence-associated secretory phenotype gene expression.; p53-serine15 phosphorylation is upregulated in keloids, as identified by phosphospecific protein microarray and western blotting.; FOXO4-DRI induces apoptosis and reduces G0/G1 phase cells in keloid organ cultures and fibroblasts.; FOXO4-DRI treatment causes nuclear exclusion of p53-pS15, counteracting senescence and apoptosis resistance.
Patients with pulmonary arterial hypertension had increased lung senescence markers p16, p21, and DNA damage markers compared to controls.; Elimination of senescent cells via suicide gene or senolytic drugs (ABT263, FOXO4-DRI) increased right ventricular systolic pressure and vessel remodeling in mice.; Senolytic interventions led to loss of pulmonary endothelial cells and aggravated pulmonary hypertension in multiple animal models.; Monocrotaline-induced pulmonary hypertension in rats was initially slightly reduced by ABT263 but worsened after 3 weeks with endothelial cell loss.
Frequently asked questions
What is FOXO4-DRI?
**Mechanism of Action** FOXO4-DRI (Proxofim) is a D-retro-inverso peptide designed to selectively target senescent cells. It disrupts the interaction between FOXO4 and p53, a key survival pathway in senescent cells. By blocking FOXO4-p53 binding, the peptide releases p53 to translocate to the mitochondria, where it tri
How does FOXO4-DRI work?
D-retro-inverso peptide that disrupts FOXO4-p53 interaction to selectively trigger apoptosis in senescent cells (senolytic).
What is the research status of FOXO4-DRI?
FOXO4-DRI is currently classified as preclinical, with 17 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of FOXO4-DRI?
FOXO4-DRI has a molecular weight of approximately 5358 g/mol (formula C228H388N86O64).
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