Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor
作者： M. Raymond V. Finlay , Mark Anderton , Susan Ashton , Peter Ballard , Paul A. Bethel
DOI: 10.1021/JM500973A
关键词: EGFR inhibitors 、 Pharmacology 、 Epidermal growth factor receptor 、 Mutation 、 T790M 、 Wild type 、 Drug resistance 、 Biology 、 Lung cancer 、 Rociletinib
摘要: Epidermal growth factor receptor (EGFR) inhibitors have been used clinically in the treatment of non-small-cell lung cancer (NSCLC) patients harboring sensitizing (or activating) mutations for a number years. Despite encouraging clinical efficacy with these agents, many resistance develops leading to disease progression. In most cases, this is form T790M mutation. addition, EGFR wild type inhibition inherent agents can lead dose limiting toxicities rash and diarrhea. We describe herein evolution an early, mutant selective candidate AZD9291, irreversible inhibitor both (EGFRm+) selectivity over receptor. Following observations significant tumor preclinical models, was administered positive EGFR-TKI resistant NSCLC early has observed, acc...
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