FOXO4-DRI is a cell-permeable peptide antagonist that blocks the interaction of FOXO4 and p53. FOXO4-DRI is a senolytic peptide that induces apoptosis of senescent cells.
体外研究
FOXO4-DRI (25 mM; 3 days) induces nuclear exclusion of active p53 and triggers apoptosis in senescent TM3 Leydig cells [1].
FOXO4-DRI (25 μM; 5 days) significantly reduced the senescence level of PDL9 cells [2].
Cell Viability Assay
Cell Line:
Senescent Leydig cells
Concentration:
25 mM
Incubation Time:
3 days
Result:
Reduced the viability of senescent as compared to normal TM3 Leydig cells.
Apoptosis Analysis
Cell Line:
Senescent Leydig cells
Concentration:
25 mM
Incubation Time:
3 days
Result:
The apoptosis rate increased from 10% to 27%.
Western Blot Analysis
Cell Line:
PDL9 cells
Concentration:
25 μM
Incubation Time:
5 days
Result:
Decreased the protein levels of representative senescent markers, including p16, p21, and p53.
RT-PCR
Cell Line:
PDL9 cells
Concentration:
25 μM
Incubation Time:
5 days
Result:
Enhanced SOX9 expression, and reduced MMP12 and MMP13 expression.
体内研究
FOXO4-DRI (5 mg/kg; i.p.; administered every other day for three doses) alleviates testosterone deficiency in naturally aging mice and improves the testicular microenvironment.
Animal Model:
Naturally aged male C57BL/6 mice (20-24 months old)
Dosage:
5 mg/kg
Administration:
Intraperitoneal injection, every other day for three administrations
Result:
Increased serum testosterone levels. Increased levels of both 3β-HSD and CYP11A1. Decreased interstitial SA-β-gal activity and lowered levels of senescence-associated proteins p53, p21, and p16. Decreased the levels of IL-1β, IL-6 and TGF-β.
分子式
C228H388N86O64
分子量
5358.06
CAS号
2460055-10-9
中文名称
FOXO4-DRI
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Zhang C, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY). 2020 Jan 20;12(2):1272-1284.
[2]. Huang Y, et al. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Front Bioeng Biotechnol. 2021 Apr 29;9:677576.