Design, synthesis and structure-activity relationship analysis of dibenzodiazepinone derivatives against Osimertinib resistant NSCLC.

ABSTRACT: Lung cancer, particularly NSCLC, is the leading cause of cancer-related deaths worldwide, accounting for over 80% of cases. Mutations in the epidermal growth factor receptor (EGFR) are key drivers of NSCLC. Although three generations of EGFR tyrosine kinase inhibitors (TKIs) have been developed, resistance limits their efficacy. The dibenzodiazepinone scaffold exhibits diverse biological activities, however, reports on its derivatives for treating NSCLC with EGFR mutations, particularly triple mutations, are rare. Guided by the binding model of DDC4002 with EGFR^T790M/V948R, this study synthesized and characterized 36 dibenzodiazepinone analogues, evaluating their antiproliferative activity against NSCLC cell lines. Structure-activity relationship analysis highlighted the importa

SUBMITTER: Jin C 

PROVIDER: S-EPMC12613096 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature