Also known as Proxofim · FOXO4 D-Retro-Inverso peptide
A senolytic D-retro-inverso peptide that selectively triggers apoptosis in senescent cells by disrupting the FOXO4–p53 interaction.
Research refreshed
FOXO4-DRI is one of the most cited experimental senolytics — peptides designed to clear senescent ("zombie") cells that accumulate with age. It works by disrupting the interaction between the transcription factor FOXO4 and the tumor-suppressor p53, a partnership that senescent cells rely on to avoid self-destruction. Breaking it pushes p53 out of the nucleus and drives those cells into apoptosis, while sparing normal cells. It is built as a D-retro-inverso peptide — the sequence reversed and made from D-amino acids — to resist breakdown in the body.
FOXO4-DRI came out of a 2017 Cell paper from Peter de Keizer’s group (Baar et al., Erasmus MC) that gave the young field of senolytics one of its most striking results. Senescent cells — damaged cells that stop dividing but refuse to die, secreting inflammatory signals — build up with age and drive tissue decline. The insight was that many of them survive by using the protein FOXO4 to keep p53, the cell’s own suicide switch, sequestered and inactive.
FOXO4-DRI is a decoy that occupies FOXO4’s binding site, freeing p53 to trigger apoptosis specifically in cells that depend on that leash. In aged and progeroid mice, the peptide reportedly restored fitness, fur density, and kidney function. To survive as a drug it is synthesized as a D-retro-inverso peptide — the amino-acid order reversed and every residue a mirror-image D-form — which keeps its shape and binding while making it highly resistant to proteases. It is an early-stage research compound (sometimes labeled Proxofim), not FDA-approved, with essentially no human safety data.
Disrupts the FOXO4–p53 interaction in senescent cells, causing p53 nuclear exclusion and cell-intrinsic apoptosis (a senolytic effect); the D-retro-inverso design confers protease resistance.
Behind every vial of FOXO4-DRI is the same exacting pipeline every research peptide runs — but the chemistry plays out differently for this molecule. Here is how FOXO4-DRI, specifically, is brought into being.
On paper, FOXO4-DRI is C228H388N86O64 — about 5,358.2 daltons of precisely arranged atoms. Before a single bond is made, the target sequence, salt form, and purity threshold are written down as the contract the finished material must meet.
FOXO4-DRI is assembled by solid-phase peptide synthesis — the chain grows one protected residue at a time on resin, and what you fail to build cleanly here you pay to remove later.
The crude mixture — FOXO4-DRI plus its deletions and side products — is then separated on preparative HPLC, and where the cut is taken decides the difference between a genuinely pure peptide and a barely-passable one.
A real batch of FOXO4-DRI proves itself: identity confirmed by mass spectrometry against its ~5,358.2 Da, purity read directly off an analytical HPLC trace, water and counterion content measured. That batch-specific certificate of analysis is the only honest way to know what is actually in a vial of FOXO4-DRI — and a short, cold, accountable chain of custody is how that purity survives the trip to your bench.
FOXO4-DRI is a long D-retro-inverso peptide — the sequence reversed and built entirely from D-amino acids for protease resistance. Every residue is a specialty D-building block over a long chain, making it a demanding specialty solid-phase synthesis where all-D coupling efficiency and deletion-sequence control dominate.
Don't judge a vial by its cake. A fluffy, good-looking lyophilized powder reflects bulking agents and freeze-drying parameters — not purity. Insist on a batch-specific certificate of analysis.
FOXO4-DRI is a senolytic peptide that selectively kills senescent cells by disrupting the FOXO4–p53 interaction, freeing p53 to trigger those cells’ apoptosis.
The peptide’s sequence is reversed and built from D-amino acids (mirror-image residues), which preserves its binding shape while making it highly resistant to protease breakdown.
A compound that selectively removes senescent ("zombie") cells — damaged cells that stop dividing but resist death and secrete inflammatory signals associated with aging.
No — it is an early-stage research compound with essentially no human data, not FDA-approved. This page is a research and educational reference.
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