Discovery of 5‐(1‐benzyl‐1H‐imidazol‐4‐yl)‐1,2,4‐oxadiazole derivatives as novel RIPK1 inhibitors via structure‐based virtual screening

Abstract

AbstractRIPK1 plays a key role in necroptosis and is associated with various inflammatory diseases. Using structure‐based virtual screening, a novel hit with 5‐(1‐benzyl‐1H‐imidazol‐4‐yl)‐1,2,4‐oxadiazole scaffold was identified as an RIPK1 inhibitor with an IC50 value of 1.3 μM. Further structure–activity relationship study was performed based on similarity research and biological evaluation. The molecular dynamics simulation of compound 2 with RIPK1 indicated that it may act as a type II kinase inhibitor. This study provides a highly efficient way to discover novel scaffold RIPK1 inhibitors for further development.