articleCancer DiscoverySep 25, 2013GREEN OA

Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

AOAnnette O. WalterRTRobert Tjin Tham SjinHJHenry J. HaringsmaKOKadoaki OhashiJSJing Sun

Vanderbilt University · National Cancer Institute · +3 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

UNLABELLED: Patients with non-small cell lung cancer (NSCLC) with activating EGF receptor (EGFR) mutations initially respond to first-generation reversible EGFR tyrosine kinase inhibitors. However, clinical efficacy is limited by acquired resistance, frequently driven by the EGFR(T790M) mutation. CO-1686 is a novel, irreversible, and orally delivered kinase inhibitor that specifically targets the mutant forms of EGFR, including T790M, while exhibiting minimal activity toward the wild-type (WT) receptor. Oral administration of CO-1686 as single agent induces tumor regression in EGFR-mutated NSCLC tumor xenograft and transgenic models. Minimal activity of CO-1686 against the WT EGFR receptor was observed. In…

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627
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Authors

30

Topics & keywords

Topics
Keywords
  • T790M
  • EGFR inhibitors
  • Mutant
  • Epidermal growth factor receptor
  • Cancer research
  • Tyrosine-kinase inhibitor
  • Mutation
  • Pharmacology
UN Sustainable Development Goals
  • Good health and well-being
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