FOXO4-DRI
A D-retro-inverso peptide designed to disrupt the FOXO4-p53 interaction in senescent cells, studied as a senolytic agent that selectively induces apoptosis in aging cells.
Also referenced as: Proxofim, FOXO4-D-Retro-Inverso
Also appears in: Other
This name primarily lives in the research market and should not be read like an approved pharmaceutical product.
Primary lane: Longevity. Also surfaces under Other for browsing and discovery.
Proxofim, FOXO4-D-Retro-Inverso
No FDA label signal · 0 trials · 18 PubMed results
Current evidence for FOXO4-DRI is limited to laboratory or animal studies — there are no name-matched human trials with reported results. Any claims about effects in people are not yet backed by clinical data.
FOXO4-DRI has no clinical trials that name it and 18 PubMed-indexed publications and is not FDA-approved. Current evidence is preclinical or mechanistic.
Re-checked nightly against the registries — tracked since 2026-07-09. No band changes yet.
Grades evidence strength, not efficacy or safety. Research-use context; not medical advice. Graded 2026-07-13 from PubMed, ClinicalTrials.gov, ISRCTN, openFDA, Health Canada, and OpenAlex — computed deterministically and refreshed nightly, with a retraction check. How we grade →
What is FOXO4-DRI?
FOXO4-DRI is a modified peptide engineered to interfere with how senescent cells (damaged, non-dividing cells that accumulate with age) resist apoptosis. It was developed by Peter de Keizer’s group at Erasmus University Medical Center as part of a broader effort to create targeted senolytic therapies.
How it works
Senescent cells avoid programmed cell death through a specific protein interaction:
- FOXO4-p53 axis — in senescent cells, the transcription factor FOXO4 binds to p53 and sequesters it in the nucleus, preventing p53 from triggering apoptosis at the mitochondria (Baar et al., Cell, 2017)
- D-retro-inverso design — FOXO4-DRI uses D-amino acids in a reversed sequence, making it protease-resistant while maintaining binding affinity. It competitively displaces the natural FOXO4-p53 interaction
- Selective apoptosis — by freeing p53, the peptide allows senescent cells to undergo apoptosis while leaving healthy cells unaffected, since healthy cells do not depend on the FOXO4-p53 interaction for survival
Research status
The foundational study was published in a high-impact journal:
- Baar et al. (2017) demonstrated that FOXO4-DRI selectively induced apoptosis in senescent cells and restored fitness, fur density, and renal function in naturally aged and fast-aging mice (Cell, 169(1):132–147)
- The same study showed the peptide neutralized senescent cell resistance to apoptosis in human IMR90 fibroblasts
No human clinical trials have been registered. The peptide is large (approximately 4.5 kDa), expensive to synthesize, and the D-retro-inverso format presents manufacturing challenges for scale.
Key considerations
- One of the few senolytics with a well-characterized, selective mechanism published in a top-tier journal
- Significantly more expensive than other research peptides due to synthesis complexity (D-amino acids, long sequence)
- No human pharmacokinetic, dosing, or safety data exists
- The senolytic field is active but most clinical development focuses on small molecules (dasatinib + quercetin) rather than peptide senolytics