An irreversible inhibitor of mutant EGFRs
Naquotinib is an irreversible inhibitor of mutant EGF receptors (EGFRs).1 It inhibits proliferation of Ba/F3 cells expressing various EGFR mutations, including deletion of exon 19, deletion of exon 19 plus a T790M mutation, L858R, and L858R plus the T790M mutation (IC50s = 9, 10, 11, and 9 nM, respectively). It is selective for these mutations over the triple mutations that include exon 19 deletion plus T790M and C797S and L858R plus T790M and C797S and over wild-type EGFR (IC50s = 235, 1,994, and 830 nM, respectively). It reduces phosphorylated levels of EGFR, AKT, and ERK and decreases cell viability in non-small cell lung cancer (NSCLC) cells and in Ba/F3 cells carrying an exon 20 insertion mutation. Naquotinib (50 mg/kg per day) also reduces tumor growth in a PC-9/NaqRc2 mouse xenograft model.2
1.Hirano, T., Yasuda, H., Hamamoto, J., et al.Pharmacological and structural characterizations of naquotinib, a novel third-generation EGFR tyrosine kinase inhibitor, in EGFR-mutated non-small cell lung cancerMol. Cancer Ther.17(4)740-750(2018) 2.Ninomiya, K., Ohashi, K., Makimoto, G., et al.MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinibSci. Rep.8(1)1955(2018)
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