ERK-MYD88 inhibitor EI-52 is a small molecule inhibitor of ERK-MYD88 interaction, binds ERK1/2 (Kd=4.3/2.1 uM), inhibits ERK1/2-MYD88 interaction with IC50 of 3.1/14.7 uM in HTRF assays, induces cancer cell death.
EI-52 inhibits endogenous ERK-MYD88 interaction in HCT116 cells.
EI-52 strongly inhibits MYD88 interaction with WT ERK, does not inhibit its interaction with D319N ERK, Asp319 is critical for EI-52 binding to ERK and inhibition of ERK-MYD88 PPI.
EI-52 (8 uM) induced a rapid and robust cancer cell death in human colon cancer cells HCT116 (K-RasG13D).
EI-52 modifies ERK activity and localization, leading to integrated stress response and apoptosis in cancer cells.
EI-52 does not disrupts the cell cycle, without affecting ERK phosphorylation or ERK1/2 kinase activity.
EI-52 induces apoptosis of Lewis lung carcinoma (LLC) cells in vitro (IC50 = 4 μM).
EI-52 (25 or 50 mg/kg, vehicle (PBS, 40% PEG 400, 20% DMSO), i.p.) displays anti-tumor activity in mice and in patient-derived LCC tumor model.