4EGI-1

4EGI-1 is an inhibitor of eIF4E/eIF4G interaction, with a K_d of 25 μM against eIF4E binding. IC50 & Target: Kd: 25 μM (eIF4E/eIF4G)^[1] In Vitro: 4EGI-1 is an inhibitor of eIF4E/eIF4G interaction, with a K_d of 25 μM against eIF4E binding. 4EGI-1 disrupts the eIF4F complex and inhibits expression of oncogenic proteins in mammalian cells. 4EGI-1 (0-40 μM) also exhibits proapoptotic activity and inhibits the growth of multiple cancer cell lines^[1]. 4EGI-1 is cytotoxic to breast cancer cells, such as SKBR-3, MCF-7 and MDA-MB-231 cells, with the IC₅₀ of appr 30 μM, and to the non-CSCs (Cancer stem cells), the IC₅₀ is about 22 μM. 4EGI-1 enhances breast CSC differentiation (40 μM), and suppresses breast CSC induced HUVEC tube-like structure formation (8 μM). Moreover, 4EGI-1 selectively inhibits translation that persists in CSC maintenance and dissemination^[2]. 4EGI-1 (50 µM) impairs the formation of eIF4F complex in U87 cells. 4EGI-1 (10, 50 and 100 µM) inhibits cell proliferation via inducing apoptosis in U87 cells, and the apoptosis is via Bax activation. 4EGI-1 causes mitochondrial dysfunction, and induces ER stress via GRP-78 activation, in U87 cells^[3]. In Vivo: 4EGI-1 (75 mg/kg, i.p.) inhibits breast cancer stem cells (CSC) tumor growth and tumorangiogenesis in vivo^[2]. 4EGI-1 (75 mg/kg, i.p.) shows inhibitory effect on the tumor volume and weight in mice bearing U87 cells^[3].