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Discovery of selective irreversible inhibitors for EGFR-T790M.

ABSTRACT: 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.

SUBMITTER: Zhou W

PROVIDER: S-EPMC3035422 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Discovery of selective irreversible inhibitors for EGFR-T790M.

Zhou Wenjun W Ercan Dalia D Jänne Pasi A PA Gray Nathanael S NS

Bioorganic & medicinal chemistry letters 20101210 2

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-dep ...[more]

PMID: 21208802

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Novel mutant-selective EGFR kinase inhibitors against EGFR T790M.

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