Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.
1/5 보강
Inhibitors targeting mutant EGFR remain a persistent need in combating drug resistance in non-small cell lung cancer.
APA
Damghani T, Song S, et al. (2026). Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.. ACS medicinal chemistry letters. https://doi.org/10.1021/acsmedchemlett.5c00725
MLA
Damghani T, et al.. "Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting.." ACS medicinal chemistry letters, 2026.
PMID
41684669 ↗
Abstract 한글 요약
Inhibitors targeting mutant EGFR remain a persistent need in combating drug resistance in non-small cell lung cancer. To better understand the molecular factors involved in targeting T790M and C797S mutations, we determined X-ray cocrystal structures of fourth-generation inhibitors BI-8128 and BI-4732. Analysis from molecular dynamics and thermodynamic integration calculations correlated with biochemical and cellular measurements indicate that BI-8128 binds the double T790M/C797S more strongly than the single mutations individually. This observation showcases strengths in the design of these fourth-generation EGFR inhibitors as profile criteria require drugs to inhibit an array of oncogenic and drug resistance mutations.
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Supplementary Material
Supplementary Material
Supporting Information DocumentASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00725.
Methods (protein expression, crystallization, biochemical activity assays, molecular dynamics simulations), crystallography and refinement statistics, extended structural images (PDF)
Supporting Information DocumentASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00725.
Methods (protein expression, crystallization, biochemical activity assays, molecular dynamics simulations), crystallography and refinement statistics, extended structural images (PDF)
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