Chemical Structures and Structural Binding Modes of the BRAF Inhibitors.

<p>Chemical structures of studied BRAF inhibitors: (A) PLX4720, (B) Vemurafenib (B), PLX7904 (C) and Dabrafenib (D). (E) The binding modes of the BRAF inhibitors in the first binding site (monomer A). PLX4720 (in green), Vemurafenib (in red), PLX7904 (in blue), and Dabrafenib (in cyan). (F) The binding modes of the BRAF inhibitors in the second binding sites (monomer B). Among studied inhibitors, only PLX4720 (in green) and Dabrafenib (in cyan) bind to the second monomer. Note structural similarity of the inhibitor binding mode and DFG-in/αC-out kinase conformation in the first monomer, while alternative inhibitor binding modes and conformational variability in the second monomer.