Abstract
Lung cancer remains a leading cause of global cancer-related mortality, emphasizing the need for innovative strategies to combat resistance to the first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), Gefitinib. This study aimed to discover and evaluate small molecule compounds selectively inhibiting Gefitinib resistance. A compound library was screened against adenocarcinoma (A549), EGFR-mutant NSCLC (H1975 and PC9), and Gefitinib-resistant NSCLC (PC9GR) cell lines. The study identified W1 as a promising lead compound, and its derivative, compound W3, exhibited excellent efficacy in PC9 and PC9GR cells. These findings underscore the potential of W3, an 4-anilinopyrimidine derivative, as an inhibitor of Gefitinib resistance in NSCLC. This research contributes valuable insights to the ongoing efforts in developing effective and sustainable treatment options for lung cancer patients facing EGFR-TKI resistance.
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