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• W2790667641 abstract "A new class of acrylamide-substituted quinazoline derivatives with enhanced inhibitory activity against mutant EGFR T790M enzyme were synthesized. Among them, compound 10b displayed the strongest inhibitory potency to block the phosphorylation of the EGFR T790M enzyme, with an IC50 value of 4.3 nM. Compared with the lead compound gefitinib, compound 10b significantly strengthened the activity against EGFR T790M (194 times higher). Furthermore, compound 10b only exhibited moderate activity against wild type EGFR, with an IC50 of 105.0 nM, suggesting its improved selectivity over the T790M-mutated EGFR. In addition, compound 10b also showed stronger activity against H1975 cells harboring the EGFR T790M mutation than gefitinib. Moreover, compound 10b has low inhibitory activity toward the normal HBE cells (IC50 > 34.04 μM), indicating its low cell cytotoxicity. Overall, this modification provided a new insight to design covalent binding EGFRT790M inhibitors to prevent NSCLC resistance." @default.
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• W2790667641 date "2018-04-01" @default.
• W2790667641 modified "2023-10-18" @default.
• W2790667641 title "New acrylamide-substituted quinazoline derivatives with enhanced potency for the treatment of EGFR T790M-mutant non-small-cell lung cancers" @default.
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• W2790667641 doi "https://doi.org/10.1016/j.bioorg.2018.01.035" @default.
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