Discovery of selective irreversible inhibitors for EGFR-T790M

作者：Zhou Wenjun; Ercan Dalia; Jaenne Pasi A; Gray Nathanael S^*

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(2): 638-643.

DOI：10.1016/j.bmcl.2010.12.036

• EGFR
• Kinase inhibitor
• T790M
• Mutant selective

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

• 出版日期2011-1-15