Fig. 2: Crystal structure analysis of brigatinib complexed with EGFR kinase domain with T790M and C797S mutations.
From: A macrocyclic kinase inhibitor overcomes triple resistant mutations in EGFR-positive lung cancer
a Overall structure of the asymmetric dimer of the EGFR-T790M/C797S kinase domain. The receiver (brigatinib-bound form) and activator (apo-form) subunits of the dimer are colored green and orange, respectively. Brigatinib is shown as a magenta stick model. The structure data was deposited at PDB with ID: 8H7X. b Comparison of the structures of brigatinib-bound EGFR-T790M/C797S (green) and apo-form EGFR-T790M/C797S (orange). The “in” and “out” conformations of the brigatinib-bound and apo-form αC-helices correspond to the active and inactive conformations of the EGFR kinase domain, respectively. c Binding mode of brigatinib to EGFR-T790M/C797S. Brigatinib (magenta) and selected residues of EGFR-T790M/C797S (green) are shown as stick models.
