Discovery of selective irreversible inhibitors for EGFR-T790M

摘要: Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive inhibitors results in dramatic but short-lived responses patients EGFR mutant non small cell lung cancer. A series of novel covalent selectivity for clinically relevant T790M ‘gatekeeper’ resistance mutation relative to wild-type were discovered by library screening. representative compound 3i was obtained through a systematic SAR study guided EGFR-dependent cellular proliferation assays.