Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors.

Allosteric kinase inhibitors represent a promising new therapeutic strategy for targeting kinases harboring oncogenic driver mutations in cancers. Here, we report the discovery, optimization, and structural characterization of allosteric mutant-selective EGFR inhibitors comprising a 5,10-dihydro-11

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Copyright © 2019 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare the following competing financial interest(s): P.A.J. reports receiving commercial research grants from AstraZeneca, Boehringer Ingelheim, Astellas Pharmaceuticals, PUMA, Eli Lilly, and Takeda Oncology, has ownership interest (including stock, patents, etc.) in Gatekeeper Pharmaceuticals and LOXO Oncology, is a consultant or advisory board member for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Roche/Genentech, Pfizer, Merrimack Pharmaceuticals, Chugai Pharmaceuticals, Araxes Pharmaceuticals, Mirati, Ignyta, and LOXO Oncology, and has received other remuneration from Labcorp. M.J.E. reports receiving a commercial research grant from Novartis Institutes for Biomedical Research, reports receiving other commercial research support from Takeda, and has been a consultant for Novartis Institutes for Biomedical Research. N.S.G. reports receiving a commercial research grant from Takeda and is a consultant or advisory board member for C4, Petra, Syros, Soltego, and B2S Bio. No potential conflicts of interest were disclosed by the other authors.