2. Academic Validation
  3. Discovery of selective irreversible inhibitors for EGFR-T790M

Discovery of selective irreversible inhibitors for EGFR-T790M

  • Bioorg Med Chem Lett. 2011 Jan 15;21(2):638-43. doi: 10.1016/j.bmcl.2010.12.036.
Wenjun Zhou 1,  Dalia Ercan,  Pasi A Jänne,  Nathanael S Gray
Affiliations

Affiliation

  • 1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, United States.
PMID: 21208802 DOI: 10.1016/j.bmcl.2010.12.036
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.

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