CHMFL-EGFR-202

CHMFL-EGFR-202 is a potent, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant kinase, with IC₅₀s of 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases, respectively. CHMFL-EGFR-202 exhibits ～10-fold selectivity for EGFR L858R/T790M against the EGFR wild-type in cells. CHMFL-EGFR-202 adopts a covalent “DFG-in-C-helix-out” inactive binding conformation with EGFR, with strong antiproliferative effects against EGFR mutant-driven nonsmall-cell lung cancer (NSCLC) cell lines^[1]. IC50 & Target:IC50: 5.3 nM (EGFR T790M), 8.3 nM (EGFR), 8.1 nM (BLK), 24.5 nM (BTK), 8.1 nM (ERBB2), 3.2 nM (ERBB4), 111.0 nM (BMX) and 161.0 nM (MEK1)^[1] In Vitro: CHMFL-EGFR-202 potently inhibits EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M^[1].
CHMFL-EGFR-202 displays strong binding affinities against wild-type, G719C/S, L858R, L858R/T790M, L861Q, and T790M among EGFR wild-type and mutant kinases^[1].
CHMFL-EGFR-202 also exhibits strong binding affinities against BLK, BMX, BTK, ERBB2, ERBB4, LOK, MEK1, and MEK5 kinases (percent of control score less than 1% at 1 μM)^[1].
CHMFL-EGFR-202 trongly inhibits BLK, BTK, ERBB2 and ERBB4 with IC₅₀s of 8.1 nM, 24.5 nM, 8.1 nM and 3.2 nM, respectively^[1].
CHMFL-EGFR-202 moderately inhibits BMX and MEK1 kinases with IC₅₀ of 111.0 nM and 161.0 nM^[1].