AZD9291 binding mode and structure.

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AZD9291 binding mode and structure. AZD9291 binding mode and structure. A, structural model showing the covalent mode of binding of AZD9291 to EGFRT790M via Cys797. Shown is the pyrimidine core forming two hydrogen bonds to the hinge region (Met793), orientation of the indole group adjacent to the gatekeeper residue, the amine moiety positioned in the solvent channel, and the covalent bond formed to Cys797 via the acrylamide group of AZD9291. B, chemical structure of AZD9291. Darren A.E. Cross et al. Cancer Discovery 2014;4:1046-1061 ©2014 by American Association for Cancer Research