Novel Dual-Target Kinase Inhibitors of EGFR and ALK Were Designed, Synthesized, and Induced Cell Apoptosis in Non-Small Cell Lung Cancer.

ALK-positive NSCLC coexisting with EGFR mutations is a frequently occurring clinical phenomenon. Targeting ALK and EGFR simultaneously may be an effective way to treat these cancer patients. In this study, we designed and synthesized ten new dual-target EGFR/ALK inhibitors. Among them, the optimal compound 9j exhibited good activity with IC50 values of 0.07829 ± 0.03 µM and 0.08183 ± 0.02 µM against H1975 (EGFR T790M/L858R) and H2228 (EML4-ALK) cells, respectively. Immunofluorescence assays indicated that the compound could simultaneously inhibit the expression of phosphorylated EGFR and ALK proteins. A kinase assay demonstrated that compound 9j could inhibit both EGFR and ALK kinases; thus, exerting an antitumor effect. Additionally, compound 9j induced apoptosis in a dose-dependent manner and inhibited the invasion and migration of tumor cells. All of these results indicate that 9j is worthy of further study.