Peptide reference
FOXO4-DRI
FOXO4 D-Retro-Inverso peptide ·FOXO4-p53 interfering peptide ·ProxofIm
What cited sources report about FOXO4-DRI
FOXO4-DRI is a D-amino-acid retro-inverso peptide patterned on the FOXO4 transactivation domain and designed to disrupt the FOXO4-p53 interaction that the original investigators reported as protective in senescent cells. The peptide is investigational; it has no FDA-approved indication, no PCAC nomination, and no marketing authorization in any major jurisdiction. The summaries below report what individual cited sources state; this page does not assert claims beyond what those sources report.
Baar et al. (2017) — Cell
The originating paper from the de Keizer group at Erasmus University Medical Center Rotterdam introduced FOXO4-DRI as a tool peptide engineered to interfere with FOXO4 binding to p53. The authors reported that, in cultured senescent cells and in fast-aging Xpd-TTD and naturally aged mouse models, the peptide was associated with selective senescent-cell apoptosis and with partial restoration of fitness, fur density, and renal function. They noted that work was preclinical and that no human studies had been conducted.
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.
Li et al. (2024) — Experimental Gerontology
A mouse study from Sun Yat-sen University documented spermatogenic parameters in aged males following FOXO4-DRI exposure. The authors reported induction of apoptosis in senescent Leydig cells and a reduction in selected senescence-associated secretory phenotype (SASP) factors, with concurrent improvements in germ-cell proliferation markers compared with vehicle controls.
FOXO4-DRI…induced apoptosis in senescent Leydig cells, reduced the secretion of certain Senescence-Associated Secretory Phenotype
Kong et al. (2025) — Communications Biology
A 2025 in-vitro study characterized senescent fibroblast burden in keloid tissue and exposed keloid organ cultures and primary fibroblasts to FOXO4-DRI. The authors observed apoptosis induction in pro-senescence models alongside p53-serine15 nuclear exclusion, and reported a reduction of G0/G1-phase cells. The work was limited to ex-vivo and in-vitro endpoints with no in-human data.
FOXO4-DRI promotes apoptosis and decreases G0/G1 phase cells in pro-senescence models of keloid organ cultures and fibroblasts, accompanied with p53-pS15 nuclear exclusion.
Coverage notes
The published FOXO4-DRI literature is preclinical. The originating Baar et al. (2017) paper remains the principal reference for mechanism and in-vivo mouse data, with subsequent reports extending the model to additional senescent cell types (Leydig, fibroblast, endothelial). No registered FDA-regulated clinical trials of FOXO4-DRI in humans were identified in the cited sources. There is no PCAC nomination on the public docket and no FDA approval. PubChem does not host a curated CID record for the FOXO4-DRI sequence as of this writing, so the chemistry summary above is drawn from the originating paper.