Fig. 4: Structural characterization of additional inhibitor combinations.
From: Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors
a Structure of EGFR(T790M/V948R) in complex with mavelertinib and JBJ-125 (PDB 7JXK, light gray) and P-loop comparison with AMP-PNP+JBJ-125 (PDB 7JXP, gray) and mavelertinib (PDB 7JXI, black). b Crystal structure of EGFR(T790M/V948R) in complex with naquotinib and JBJ-063 (PDB 7LG8, light gray) and P-loop comparison with AMP-PNP+JBJ-063 (PDB 7K1I, gray) and naquotinib (PDB 5Y9T, black). c Crystal structure of EGFR(L858R/V948R) in complex with osimertinib and JBJ-063 (PDB 7K1I). Comparison of P-loop conformation in complex with osimertinib (PDB 4ZAU) in black, AMP−PNP+JBJ−063 in gray (PDB 7JXQ), and osimertinib+JBJ−063 in light gray. F723 contacts the allosteric inhibitor and occludes the putative entrance and exit tunnel to the allosteric site.
