eIF4E/eIF4G PPI-IN-1 is an inhibitor that disrupts the interaction between eIF4E and eIF4G, exhibiting a dissociation constant (KD) of 20.2 μM for the eIF4E protein. It demonstrates antitumor effects through various mechanisms, including modulation of eIF4E activity via inhibition of the Ras/MAPK/eIF4E signaling pathway, influencing apoptosis and cell migration. Additionally, eIF4E/eIF4G PPI-IN-1 inhibits the growth of HepG2 xenografted tumors in nude mice and is relatively non-toxic to mice.

eIF4E:20.2 μM (Kd)

eIF4E/eIF4G PPI-IN-1 (Compound A37) at a concentration of 25 μM exhibits inhibitory activity against cancer cell lines A549, Hela, HepG2, and MCF-7, with inhibition rates of 98.08%, 81.74%, 100.78%, and 78.52% respectively. It hinders the proliferation of these cells with IC50 values of 4.59 μM, 2.69 μM, 2.22 μM, and 3.45 μM. In HEK-293T cells, it shows low cytotoxicity (IC50 of 40 μM). eIF4E/eIF4G PPI-IN-1 (1-5 μM, 48 hours) induces apoptosis in cancer cells by modulating the expression of Bcl-2, Bax, and C-Caspase-3 proteins in HepG2 cells. Additionally, at 2.5 μM for 12 and 24 hours, it inhibits HepG2 cell migration. The compound (1-5 μM, 48 hours) does not cause significant cell cycle arrest in HepG2 cells. Furthermore, it exerts antitumor effects by inhibiting the expression of Ras, p-MNK, p-ERK, and p-eIF4E in HepG2 cells.

eIF4E/eIF4G PPI-IN-1 (Compound A37) administered intraperitoneally at doses of 25 mg/kg and 50 mg/kg once daily for 18 days inhibits the growth of HepG2 cells in a HepG2 xenograft mouse model.