Fig. 8: Mechanisms of RAF inhibitors action.

Scheme of four distinct mechanisms of RAF inhibitors action and representative RAF inhibitors for each mechanism. This work revealed that PHI1 displays a distinct structural, inhibitory, and therapeutic mode of action compared to previously characterized αC-IN and αC-OUT RAF inhibitors. Moreover, Ponatinib, an FDA-approved inhibitor, is an effective inhibitor of BRAF monomers and RAF dimers with a distinct structural binding mode.