FOXO4-DRI

FOXO4-DRI is a synthetic D-retro-inverso peptide derived from the FOXO4 transcription factor and engineered to act as a senolytic — a compound that selectively eliminates senescent cells. The "DRI" suffix indicates D-amino-acid retro-inverso peptide synthesis: the residues are D-amino acids and the sequence is reversed, producing a topology functionally equivalent to the original L-amino-acid sequence but with greatly improved protease resistance.

Approximate molecular weight 5850 Da. ChEMBL ID CHEMBL4743114. The compound was first characterised by Baar and colleagues in 2017 as a tool for senescent-cell elimination in ageing-biology research.

Senescent cells accumulate with age and contribute to tissue dysfunction through the senescence-associated secretory phenotype (SASP). In senescent cells, FOXO4 binds and sequesters p53, preventing p53-mediated apoptosis and allowing the senescent cell to persist. FOXO4-DRI competitively disrupts the FOXO4-p53 interaction, releasing p53 and triggering apoptosis selectively in senescent cells (which have abundant nuclear FOXO4) while sparing healthy cells.

Investigated in preclinical models of age-related tissue decline, senescent-cell-associated pathology, and senolytic intervention strategies. The Baar 2017 paper showing reversal of age-related markers in mice has driven substantial research interest in the compound.

Supplied as a research-grade reference standard for laboratory use only. Not a licensed medicinal product in the United Kingdom and not approved by the MHRA for human or veterinary administration. Sale is restricted to researchers, institutions and laboratory professionals; the compound must be retained within research premises. End-user compliance with the Human Medicines Regulations 2012, the Misuse of Drugs Act 1971 (where applicable) and local institutional biosafety policy is the responsibility of the buyer.