Sulindac‐Derived Ras Pathway Inhibitors Target the Ras–Raf Interaction and Downstream Effectors in the Ras Pathway

Abstract

Tracking down the target: The biological targets of eight new Ras-pathway inhibitors were investigated. Several of the compounds were shown to inhibit the RasGTP–Raf interaction (see example shown) and NMR data strongly suggest that this inhibition is the result of direct interaction between the inhibitors and the Ras protein. An inhibitor with a target probably downstream of MAP kinase was also found.