Also known as: FOXO4-DRI TFA salt form, 2460055-10-9
Foxo4-DRI (FOXO4-DRI TFA salt form, 2460055-10-9) is classified under other / experimental, sold for research use only and not approved for human consumption.
Aggregated from the cited literature below. We summarize sources — we don't author claims.
FOXO4-DRI (fork head box O transcription factor 4-D-retro-inverso), including a TFA salt form, is a senolytic peptide reported in multiple studies to target the FOXO4–p53 axis and selectively affect senescent cell phenotypes across in vitro and in vivo disease models.
Across the provided sources, research investigated FOXO4-DRI in settings including pulmonary arterial hypertension, chondrocyte senescence, radiation-induced pulmonary fibrosis and cancer radioresistance, fibroblast/keloid senescence, bleomycin-induced pulmonary fibrosis, and endothelial cell senescence/vascular aging.
Mechanism (as reported)
Structural and mechanistic studies reported that FOXO4-DRI binds the p53 transactivation domain (p53TAD2) and forms a transiently folded complex, with both FOXO4-derived regions and a cationic cell-permeability peptide contributing to the interaction; p53 phosphorylation was reported to enhance affinity for FOXO4 and FOXO4-DRI. Mechanistic work in endothelial and fibroblast contexts reported that FOXO4-DRI disrupts FOXO4–P53 binding, promotes phosphorylated p53 nuclear exclusion, and is associated with activation of apoptosis-related signaling (including BAX and cleaved caspase-3), thereby inducing apoptosis of senescent cells.
Key findings (each cites a source)
A study in patients with pulmonary arterial hypertension and multiple animal pulmonary hypertension models reported increased lung senescence/DNA-damage markers (including p16, p21, γ-H2AX, and 53BP1) and observed that senescent vascular endothelial cells were decreased after senolytic interventions including FOXO4-DRI. [PMID 36515093]
In the pulmonary hypertension study, FOXO4-DRI (and other senolytic interventions) were reported to be associated with pulmonary hemodynamic alterations and pulmonary endothelial cell (P-EC) loss in comparison to relevant controls. [PMID 36515093]
A cell-based study reported that FOXO4-DRI treatment removed more than half of cells in in vitro expanded human chondrocytes at higher expansion (PDL9) while not significantly affecting minimally expanded control cells (PDL3). [PMID 33996787]
In the chondrocyte study, FOXO4-DRI treatment was reported to reduce senescence levels in PDL9 chondrocytes and to lower senescence-relevant secretory factors; pellet-culture results were reported not to show enhanced chondrogenic potential after FOXO4-DRI pretreatment. [PMID 33996787]
A cancer/radiation study reported that inducing senescence-like CAF apoptosis using FOXO4-DRI produced radiosensitizing effects on NSCLC cells in vitro and in vivo. [PMID 34877934]
In that same radiation/cancer study, FOXO4-DRI was reported to have an effect on alleviating radiation-induced pulmonary fibrosis in vivo by targeting senescence-like fibroblasts. [PMID 34877934]
A molecular structural study reported solution NMR structural models showing FOXO4-DRI binding to the disordered p53 transactivation domain region (p53TAD2) and forming a transiently folded complex; the study also reported that p53 phosphorylation enhances affinity for FOXO4 and FOXO4-DRI. [PMID 40593617]
A keloid fibroblast study reported that FOXO4-DRI promoted apoptosis and decreased G0/G1 phase cells in pro-senescence keloid organ culture/fibroblast models, accompanied by p53-serine 15 phosphorylation-linked nuclear exclusion. [PMID 39994346]
A bleomycin-induced pulmonary fibrosis study reported that FOXO4-DRI decreased senescent cells, downregulated SASP components, and attenuated morphological changes and collagen deposition in a mouse model, while also reporting changes in cell populations (increased AEC2 and fibroblasts; decreased myofibroblasts). [PMID 35510614]
A related pulmonary fibrosis study reported that FOXO4-DRI disrupted the FOXO4-p53 complex and was associated with p53 nuclear exclusion, with milder pathological changes and less collagen deposition in a FOXO4-DRI therapeutic group compared with a BLM-induced group. [PMID 37074394]
In the fibroblast/pulmonary fibrosis study, FOXO4-DRI was reported to reset intranuclear p53 distribution and decrease total ECM protein content in the tested models. [PMID 37074394]
A vascular aging/endothelial mechanism study reported that FOXO4-DRI disrupts FOXO4–P53 interaction and is associated with activation of a p53/BCL-2/caspase-3 pathway to promote selective apoptosis of senescent endothelial cells, including effects on phosphorylated p53 nuclear exclusion and downstream markers such as BAX and cleaved caspase-3. [PMID 41625068]
Independent HPLC purity tests (42)
Real third-party HPLC results aggregated from Peptigrity, each attributed to the lab that ran it — average purity 99.6% across 42 tests. Not our verdict.
Meng J, Li Y, Wan C, Sun Y, Dai X, Huang J · JCI insight · 2021 · PMID 34877934
FAQ
What is Foxo4-DRI?
Foxo4-DRI (FOXO4-DRI TFA salt form, 2460055-10-9) is classified under other / experimental, sold for research use only and not approved for human consumption. Research goals associated with it include longevity & cellular aging.
Is Foxo4-DRI FDA-approved?
No. Foxo4-DRI is sold for research use only and is not approved for human consumption.
What does the research on Foxo4-DRI say?
peptideone aggregates 9 references from PubMed for Foxo4-DRI. The summary on this page digests them with citations; we summarize sources and make no efficacy claims.