4EGI-1 is a disruptor of the eIF4E/eIF4G interaction, with a binding dissociation constant (Kd) of 25 μM against eIF4E. It interferes with the eIF4F complex formation and reduces oncogenic protein expression in mammalian cells. Additionally, 4EGI-1, in concentrations up to 40 μM, displays proapoptotic activities and curtails the proliferation of various cancer cell lines[1]. 4EGI-1 shows cytotoxicity toward breast cancer cell lines like SKBR-3, MCF-7, and MDA-MB-231, achieving an approximate IC50 value of 30 μM. It is more potent against non-Cancer stem cells (CSCs) with an IC50 around 22 μM. At 40 μM, 4EGI-1 facilitates the differentiation of breast CSCs and at 8 μM, it prevents the formation of tube-like structures in HUVEC cells induced by breast CSCs. 4EGI-1 is also noted for selectively targeting translation processes important for CSC maintenance and spread[2]. In U87 cells, 4EGI-1 at 50 μM inhibits the assembly of the eIF4F complex. It suppresses cell proliferation and promotes apoptosis at concentrations of 10, 50, and 100 μM through Bax activation. Furthermore, 4EGI-1 induces mitochondrial dysfunction and triggers endoplasmic reticulum stress by activating GRP-78 in U87 cells[3].
体内研究
In vivo, 4EGI-1 administered at 75 mg/kg intraperitoneally is effective in diminishing the growth and angiogenesis of breast cancer stem cell tumors[2].
Additionally, the same dosage (75 mg/kg, i.p.) demonstrates a significant reduction in tumor volume and weight in mice implanted with U87 cells[3].
体外研究
4EGI-1 is a disruptor of the eIF4E/eIF4G interaction, with a binding dissociation constant (Kd) of 25 μM against eIF4E. It interferes with the eIF4F complex formation and reduces oncogenic protein expression in mammalian cells. Additionally, 4EGI-1, in concentrations up to 40 μM, displays proapoptotic activities and curtails the proliferation of various cancer cell lines[1].
4EGI-1 shows cytotoxicity toward breast cancer cell lines like SKBR-3, MCF-7, and MDA-MB-231, achieving an approximate IC50 value of 30 μM. It is more potent against non-Cancer stem cells (CSCs) with an IC50 around 22 μM. At 40 μM, 4EGI-1 facilitates the differentiation of breast CSCs and at 8 μM, it prevents the formation of tube-like structures in HUVEC cells induced by breast CSCs. 4EGI-1 is also noted for selectively targeting translation processes important for CSC maintenance and spread[2].
In U87 cells, 4EGI-1 at 50 μM inhibits the assembly of the eIF4F complex. It suppresses cell proliferation and promotes apoptosis at concentrations of 10, 50, and 100 μM through Bax activation. Furthermore, 4EGI-1 induces mitochondrial dysfunction and triggers endoplasmic reticulum stress by activating GRP-78 in U87 cells[3].
4EGI-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Neonatal rat ventricular cardiomyocyte
25 µM to 100 µM
1 to 24 hours
To investigate its effect on translation and eIF4F complex formation in vitro.
Circulation. 2024 Oct 15;150(16):1248-1267.
UM-HET3 mouse fibroblasts
50 µM
24 hours
To test the effect of 4EGI-1 on GPLD1 protein levels, results showed a significant increase in GPLD1 protein levels without changes in mRNA levels
Aging Cell. 2022 Sep;21(9):e13685.
HT-1080 cells
10 µM
24 hours
4EGI-1 and 4E1RCat were the two most effective inhibitors of the RSL3-induced growth inhibition of HT-1080 cells
Nat Commun. 2022 Oct 23;13(1):6318.
T cells
20 µM
40 hours
4EGI-1 inhibited the expression of CD25 and CD122 proteins, but did not affect their mRNA expression. IL-2 expression was significantly increased.
Cell Death Dis. 2017 Feb 23;8(2):e2632.
Calu-1 cells
10 µM
72 hours
4EGI-1 and 4E1RCat at 10 μM prevented erastin- or RSL3-induced ferroptosis in Calu-1 cells for 72 h
Nat Commun. 2022 Oct 23;13(1):6318.
4EGI-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
HT-1080 xenograft tumor model
Intraperitoneal injection
40 mg/kg
Once every other day for 2 weeks
4EGI-1 enhanced the anticancer activity of IKE in the HT-1080 xenograft model
Nat Commun. 2022 Oct 23;13(1):6318.
Mice
C57BL/6N mice
Intraperitoneal injection
50 mg/kg
Single dose 30 minutes before reperfusion
To evaluate the effects of 4EGI-1 on cardiac translation and function post-I/R injury.
Circulation. 2024 Oct 15;150(16):1248-1267.
UM-HET3 mice
UM-HET3 mice
Gavage
75 mg/kg
Once daily for 7 days
To test the effect of 4EGI-1 on GPLD1 protein levels in the liver, results showed a significant increase in GPLD1 protein levels without changes in mRNA levels
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