FOXO4-DRI
FOXO4-DRI, a peptide. A retro-inverso peptide — D-amino acids in reversed sequence, which resists proteolysis while presenting a similar side-chain surface — designed…
A retro-inverso peptide — D-amino acids in reversed sequence, which resists proteolysis while presenting a similar side-chain surface — designed to disrupt the interaction between FOXO4 and p53. Senescent cells depend on that interaction to sequester p53 in the nucleus and so avoid apoptosis; blocking it causes p53 nuclear exclusion and cell-intrinsic apoptosis SELECTIVELY in senescent cells, leaving proliferating cells alone. That selectivity is the design, and it makes this the archetype of the peptide senolytics.
PubChem CID 167312269 (C228H388N86O64), CAS 2460055-10-9. NO SEQUENCE IS STORED because no indexed abstract prints one and PubChem returns only formula and mass; the retro-inverso construction is described in the primary paper rather than specified residue by residue in any abstract. Baar 2017 (PMID:28340339, Cell) is the primary: "we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53. In senescent cells, this selectively causes p53 nuclear exclusion and cell-intrinsic apoptosis." SYSTEMS COME FROM THAT ABSTRACT'S OWN OUTCOMES rather than from the mechanism's generality: "it restored fitness, fur density, and renal function in both fast aging XpdTTD/TTD and naturally aged mice". THE DOSING REGIMEN IS NOT IN ANY ABSTRACT — no mg/kg, no route, no schedule. It lives in the paper's STAR Methods, which E-utilities does not return, so full text is the unlock and the dose block is deliberately empty rather than filled from a vendor page. ROUTE CAVEAT: all published administration is intraperitoneal, which `Route` cannot express; SC is listed because that is how the research-chemical market sells it, and no PK depends on the choice since none exists. "PROXOFIM" IS CARRIED AS AN ALIAS FOR FINDABILITY ONLY — the name appears in no PubMed record and PubChem returns nothing for it, so it must not be cited to a source. TRAP: PMID:42024235 mentions "preliminary human studies involving FOXO4-axis modulators, such as high-dose fisetin", which is fisetin and not this peptide; that sentence is the likeliest source of a claim that FOXO4-DRI has human data. Mechanism corroboration PMID:40593617 (NMR: "the disordered FOXO4-DRI binds to the disordered p53TAD2").
Sources: PMID:28340339, PMID:40593617, PMID:42510573