EGFR inhibitor 9 is a potent, selective, brain-penetrant and orally bioavailable EGFR inhibitor, exhibits potent activity in osimertinib-resistant cell lines bearing L858R/C797S and exon19del/C797S EGFR resistance mutations.
EGFR inhibitor 9 displays potent antiproliferative activity in patient-derived non-small-cell lung cancer cell lines HCC827 (EGFR mutation = exon19del), NCI-H3255 (EGFR mutation = L858R), and osimertinib-resistant engineered cell lines (Ba/F3-L858R/C797S; Ba/F3 del E746_A750/C797S) while displaying no activity in NCI-H1975 (EGFR mutation = L858R/T790M) and minimal activity in A431 cell line (overexpressed EGFRwt).
EGFR inhibitor 9 d isplays excellent activity against the NCI-H3255 NSCLC cell line bearing the common EGFRL858R mutation, with an IC50 of 7.2 nM.
EGFR inhibitor 9 also has potent activity against HCC827 NSCLC cells harboring EGFRdel E746_A750 with an IC50 of 3.1 nM.
EGFR inhibitor 9 exhibits strong activity in osimertinib-resistant engineered Ba/F3 cell lines bearing EGFRL858R/C797S and EGFRdel E746_A750/C797S.