Scientific Reference
FOXO4-DRI
Evidence profile: Predominantly preclinical
FOXO4-DRI is a 46-residue D-retro-inverso peptide designed to interfere with the interaction between the FOXO4 protein and p53. It was reported in 2017 by Baar and colleagues, who took part of the FOXO4 p53-interaction domain, joined it to a cell-penetrating sequence and built the whole peptide from D-amino acids. All published work is preclinical: cultured human cells, mouse models of ageing and of lung fibrosis, and one rodent study in which clearing senescent cells made pulmonary haemodynamics worse. No human study was identified.
Mechanism of Action
Baar and colleagues reported in 2017 that FOXO4 holds p53 in the nucleus of senescent cells, and that a peptide competing for that interaction causes p53 to leave the nucleus, followed by apoptosis in senescent cells selectively. Solution NMR work published in 2025 placed the binding site on the disordered transactivation domain of p53 and found that both the FOXO4-derived region and the cationic carrier sequence contribute. Selectivity for senescent cells is reported by several groups, in cell and rodent models only.
Molecular Information
- Type: D-retro-inverso peptide
- Length: 46 amino acids
- Molecular weight: 5358 g/mol
- Molecular formula: C228H388N86O64
- CAS: 2460055-10-9