Fig. 1

Schematic diagrams of the modeling used for the structure-based virtual database screening. a JXM and kinase domains of the EGFR protein. The structure is based on the Protein Data Bank entry 3GOP. The circled region indicates the target JXM binding site used in our virtual screening study. b The Predicted model of EE02 binding to the EGFR JXM and kinase domains. EE02 is rendered as a ball-and-stick model. The molecular surface of the EGFR JXM and kinase domains is colored to indicate electrostatic potentials: red indicates the most positively charged regions, and blue indicates the most negatively charged regions. c Specific hydrogen bonds formed between the EGFR JXM and kinase domains and EE02. The binding model was predicted by SYBYL. Only the residues that form hydrogen bonds with EE02 are shown in the explicit atomic models. d EE02 structure. e, f A549 and BT549 cells were used for the initial EGFR/EPS8 complex small-molecule inhibitor screening. The cells were treated with 10 μM EE02 as well as other small-molecule compounds for 24 h, and then the cells were harvested for analysis by a CCK-8 assay (n = 3). a-c were generated by using PyMOL