Discovery and Optimization of Potent, Efficacious and Selective Inhibitors Targeting EGFR Exon20 Insertion Mutations
Clare Thomson,
Peter Barton,
Erin Braybrooke
et al.
Abstract: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 selective inhibitor of EGFR Exon20 insertions and
has demonstrated encouraging efficacy in NSCLC E… Show more
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