Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR

ACS Medicinal Chemistry Letters
Marian C BryanTimothy P Heffron

Abstract

The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of pyridone 1, a nonselective high-throughput screening hit, to potent molecules with high levels of selectivity over wtEGFR and the broader kinome is described herein.

References

Aug 28, 2002·The Journal of Biological Chemistry·Jennifer StamosCharles Eigenbrot
Jul 31, 2004·Science·Raffaella SordellaJeffrey Settleman
Sep 23, 2006·Nature Reviews. Cancer·Mario E Lacouture
Feb 24, 2007·Nature Reviews. Cancer·Sreenath V SharmaDaniel A Haber
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cai-Hong YunMichael J Eck
May 18, 2012·Journal of Medicinal Chemistry·Huifen ChenDaniel J Burdick
Jun 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ludovico Sutto, Francesco Luigi Gervasio
Feb 1, 2014·Nature Reviews. Drug Discovery·Andrew L HopkinsCharles H Reynolds
May 8, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dalia ErcanPasi A Jänne
May 13, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthew J NiederstJeffrey A Engelman
May 15, 2015·Journal of the American Chemical Society·Melissa A LowderAlanna Schepartz

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Citations

Jun 21, 2019·Organic & Biomolecular Chemistry·Kunita Phakdeeyothin, Sirilata Yotphan
Oct 30, 2019·Current Topics in Medicinal Chemistry·Pedro de Sena M PinheiroCarlos A M Fraga
Feb 21, 2021·Bioorganic & Medicinal Chemistry Letters·Yun Zhang, Andrew Pike
Nov 7, 2019·Journal of Medicinal Chemistry·Harald EngelhardtDarryl B McConnell
Mar 7, 2020·Journal of Chemical Information and Modeling·Philipp S Schmalhorst, Andreas Bergner

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