fig3

Figure 3. Structure and kinase inhibitory activities of the new FAK inhibitors. (A-D) NSCLC cells (PC9, PC9AR, H1975, and H1975OR) were treated with Afatinib, Osimertinib, 10k, 10l, or their combinations for 24 h, followed by protein extraction. The levels of p-FAK were measured using an ELISA assay. NSCLC Cells were treated with each compound at concentrations corresponding to their respective IC₅₀ values for the indicated cell lines; (E) 2D ligand interaction diagram for compound 10k; (F) 3D complex of the FAK catalytic domain (PDB code: 6YOJ) with compound 10k; nitrogen, oxygen, and sulfur atoms are shown in blue, red, and yellow, respectively. Statistical significance: P-values were set as follows: ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, “ns” indicates a non-significant difference. The graphs were created with GraphPad Prism. FAK: Focal adhesion kinase; NSCLC: non-small cell lung cancer; PC9AR: PC9 Afatinib resistant; H1975OR: H1975 Osimertinib resistant; P-FAK: phosphorylated focal adhesion kinase; ELISA: enzyme-linked immunosorbent assay; IC₅₀: half-maximal inhibitory concentration; 2D: two-dimensional; 3D: three-dimensional; PDB: Protein Data Bank; Afa: Afatinib; Osi: Osimertinib.