FOXO4-DRI
D-retro-inverso FOXO4–p53 senolytic peptide — preclinical; PH caution; ≠ endogenous FOXO4.
Editorial review:Evidence snapshot
This drawer marks papers. It is not a plan, a dose, or a source. A paper is a bounded report. It is not a protocol. Grades name the object. They are not a safety rating.
Identity lock. FOXO4-DRI is a synthetic D-retro-inverso peptide designed to perturb FOXO4–p53 interaction and preferentially eliminate senescent cells (Baar / de Keizer-line senolytic). PubChem CID 167312269 (also 168431240 same formula record); formula C228H388N86O64 / MW 5358; CAS 2460055-10-9 (TFA-salt naming appears on records). ≠ endogenous FOXO4 transcription factor (separate drawer). Human clinical efficacy trials are absent from this pack. This drawer marks papers. It is not use advice.
Bottom line
The landmark Cell paper and subsequent mouse/in-vitro senolytic applications (fibrosis, Leydig cell aging, chondrocytes, keloid fibroblasts, endothelial senescence) are preclinical. At least one follow-on warns senescent-cell clearance can worsen pulmonary hypertension development in a model — refuse one-sided longevity glow.
Papers
Landmark senolytic demonstration
PMID 28340339 — Baar 2017
Tested: FOXO4-directed peptide inducing targeted apoptosis of senescent cells and restoring tissue homeostasis after chemotoxicity and in aging models.
Does not show: a human longevity or frailty RCT; mouse/chemotoxicity framing ≠ consumer anti-aging proof.
Mechanism follow-ons
PMID 40593617 — Bourgeois 2025
Tested: disordered p53 transactivation domain as the target of FOXO4 and the senolytic compound FOXO4-DRI.
Does not show: human clinical efficacy.
Disease / tissue preclinical applications (not human grades)
PMID 37074394 — Liu 2023
Tested: FOXO4-DRI targeting extracellular matrix production in fibroblasts and ameliorating bleomycin-induced pulmonary fibrosis in mice.
Does not show: a human IPF approval.
PMID 39994346 — Kong 2025
Tested: FOXO4-DRI inducing keloid senescent fibroblast apoptosis via nuclear exclusion of upregulated p53-Ser15 phosphorylation.
Does not show: a human keloid drug indication.
PMID 31959736 — Zhang 2020
Tested: FOXO4-DRI alleviating age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.
Does not show: a human hypogonadism RCT.
PMID 39025385 — Li 2024
Tested: FOXO4-DRI improving spermatogenesis in aged mice by reducing SASP from Leydig cells.
Does not show: human fertility therapy proof.
PMID 33996787 — Huang 2021
Tested: FOXO4-DRI selectively removing senescent cells from in-vitro expanded human chondrocytes.
Does not show: a clinical osteoarthritis disease-modification trial.
PMID 41625068 — Hu 2025
Tested: FOXO4-DRI regulating endothelial cell senescence via p53 signaling (cellular model).
Does not show: human vascular anti-aging outcomes.
Cautionary model — clearance not universally beneficial
PMID 36515093 — Born 2023
Tested: eliminating senescent cells can promote pulmonary hypertension development and progression (context includes senolytic strategies affecting FOXO4-pathway narratives).
Does not show: that senolytic peptides are categorically safe or indicated; documents potential harm framing.
What is not established
Any human clinical efficacy or approved senolytic indication for FOXO4-DRI. That clearing senescent cells is always beneficial. Equivalence of unlabeled research chemicals to Baar-peptide material. Identity with endogenous FOXO4 protein. This drawer does not provide use advice, schedules, or sourcing.
Selected sources
28340339 40593617 37074394 39994346 31959736 39025385 33996787 41625068 36515093
Reported experiences
Reported topics are not established benefits.Risks and unknowns
Compare experiences with care.
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