FOXO4-DRI

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[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Signaling Pathways >> Apoptosis >> MDM-2/p53

Research Areas >> Metabolic Disease

FOXO4-DRI (25 mM; 3 days) 引起活性 p53 的核排斥，诱导衰老 TM3 Leydig 细胞凋亡[1]。 FOXO4-DRI (25 μM; 5 days) 显著降低 PDL9 细胞的衰老水平[2]。 Cell Viability Assay[1] 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[1] Cell Line: Senescent Leydig cells Concentration: 25 mM Incubation Time: 3 days Result: The apoptosis rate increased from 10% to 27%. Western Blot Analysis[2] 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[2] Cell Line: PDL9 cells Concentration: 25 μM Incubation Time: 5 days Result: Enhanced SOX9 expression, and reduced MMP12 and MMP13 expression.

FOXO4-DRI (5 mg/kg; i.p.; every other day for three administrations) 缓解自然衰老小鼠睾丸激素分泌不足，改善睾丸微环境[1]。 Animal Model: Naturally aged male C57BL/6 mice (20-24 months old)[1] 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.

[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.