Discovery of selective and noncovalent diaminopyrimidine-based inhibitors of epidermal growth factor receptor containing the T790M resistance mutation.

doi:10.1021/jm501578n

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Article

Discovery of selective and noncovalent diaminopyrimidine-based inhibitors of epidermal growth factor receptor containing the T790M resistance mutation.

Journal of medicinal chemistry - 11 Dec 2014

Hanan Emily J, Eigenbrot Charles, Bryan Marian C, Burdick Daniel J, Chan Bryan K, Chen Yuan, Dotson Jennafer, Heald Robert A, Jackson Philip S, La Hank, Lainchbury Michael D, Malek Shiva, Purkey Hans E, Schaefer Gabriele, Schmidt Stephen, Seward Eileen M, Sideris Steve, Tam Christine, Wang Shumei, Yeap Siew Kuen, Yen Ivana, Yin Jianping, Yu Christine, Zilberleyb Inna, Heffron Timothy P

Abstract excerpt

Activating mutations within the epidermal growth factor receptor (EGFR) kinase domain, commonly L858R or deletions within exon 19, increase EGFR-driven cell proliferation and survival and are correlated with impressive responses to the EGFR inhibitors erlotinib and gefitinib in nonsmall cell lung cancer patients. Approximately 60% of acquired resistance to these agents is driven by a single secondary mutation...

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PMID: 25383627
DOI: 10.1021/jm501578n
PMCID: PMC4266342

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EGFR

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