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Article

Discovery and Optimization of Potent, Efficacious and Selective Inhibitors Targeting EGFR Exon20 Insertion Mutations.

Journal of medicinal chemistry - 13 Jun 2024

Thomson Clare, Barton Peter, Braybrooke Erin, Colclough Nicola, Dong Zhiqiang, Evans Laura, Floc'h Nicolas, Guérot Carine, Hargreaves David, Khurana Puneet, Li Songlei, Li Xiuwei, Lister Andrew, McCoull William, McWilliams Lisa, Orme Jonathan P, Packer Martin J, Swaih Aisha M, Ward Richard A, Winlow Poppy, Ye Yang

Abstract excerpt

Herein, we report the identification and optimization of a series of potent inhibitors of EGFR Exon20 insertions with significant selectivity over wild-type EGFR. A strategically designed HTS campaign, multiple iterations of structure-based drug design (SBDD), and tactical linker replacement led to a potent and wild-type selective series of molecules and ultimately the discovery of 36. Compound 36 is a potent and...

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Identifiers

PMID: 38770784
DOI: 10.1021/acs.jmedchem.4c00227

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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