EGFR-IN-1671 is a selective EGFR inhibitor with an IC50 value of 0.19 nM. It effectively inhibits various EGFR mutants, showing IC50 values of 0.109 nM for EGFR(L858R), 0.75 nM for EGFR(C797S), and less than 0.05 nM for EGFR(del19). EGFR-IN-1671 covalently binds to the catalytically conserved lysine of EGFR in live mammalian cells. By inhibiting EGFR autophosphorylation, this compound demonstrates excellent antiproliferative activity. EGFR-IN-1671 is applicable in research on non-small cell lung cancer (NSCLC), glioblastoma, and various solid tumors.

EGFR (L858R):0.109 nM

EGFR-IN-167 (Compound 26) exhibits superior in vitro activity with an IC50 of 35/1.8 nM. When tested on A431 and HCC827 cells at concentrations ranging from 1 to 100000 nM over 72 hours, it shows significant cytotoxic effects with GI50 values of 260 nM and 64 nM, respectively. It effectively inhibits malignant cell proliferation in H3255 (L858R) and Ba/F3 (C797S) cells with GI50 values of 458 nM and 112.7 nM, respectively. Additionally, EGFR-IN-167 at 0.01-10 μM over 4 hours continuously suppresses EGFR phosphorylation in A431 and HCC827 cells, retaining its inhibitory effect even after washout. In mouse liver microsomes, it has a half-life of 29.6 minutes and demonstrates favorable lipolytic stability. At a concentration of 10 μM, EGFR-IN-167 has low metabolic inhibition on five major CYP isoenzymes (CYP1A2, 2C9, 2C19, 2D6, and 3A4), all below 50%.