Dual binding site inhibitors of B-RAF kinase

Computer aided modeling guided the design of a series of diarylimidazole compounds (11–22) intended to interact with both the ATP and adjacent allosteric binding domains of B-RAF kinase. Their ability to inhibit the function of B-RAF kinase and intracellular ERK1/2 phosphorylation were evaluated.

Diarylimidazole motifs were designed to interact with both the ATP binding site and the adjacent allosteric region.Figure optionsDownload as PowerPoint slide