Foxo4-DRI

Foxo4-dri, FOXO4 D-Retro-Inverso peptide, also known as Proxofim, was first reported in 'Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging' by Baar et al.

FOXO4 DRI peptide comprising the amino acid sequence: LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRP, wherein the amino acids in said amino acid sequence are D-amino acid residues. FOXO4 D-Retro-Inverso peptide selectively induces apoptosis of senescent cells reverses effects of chemotoxicity and aging in mice.

FOXO4-DRI is a synthetic version of FOXO4, which contains D amino acids instead of L amino acids. This modification allows it to retain the functionality of the original protein and longer shelf life, and lower clearance from the body. Its most prominent function is the regulation of apoptosis in senescent cells. It inhibits FOXO4-p53 binding. Thus p53 can target pro-apoptotic genes and promote their expression. These proteins, in turn, bring about apoptosis of old cells, thereby reducing the old cell burden in tissues. This increases cellular differentiation and tissue repair,
and regrowth and decrease in “biological age.”

FOXO4 is known to help the perpetuation of aged or senescent cells.It binds to p53 and thereby prevents apoptotic death of the senescent cells. The DRI peptide prevents FOXO4-p53 interaction.

FOXO4 DRI peptide comprising the amino acid sequence: LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRP, wherein the amino acids in said amino acid sequence are D-amino acid residues. FOXO4 D-Retro-Inverso peptide selectively induces apoptosis of senescent cells reverses effects of chemotoxicity and aging in mice