Mutated EGFR-IN-3

Mutated EGFR-IN-3 (compound 3) is a potent, ATP-competitive and highly selective allosteric dibenzodiazepinone inhibitor of the EGFR(L858R/T790M) and EGFR(L858R/T790M/C797S) mutants with IC50 values of 12 nM and 13 nM, respectively[1].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

EGFRL858R/T790M:12 nM (IC50)

EGFRC797S:13 nM (IC50)

Mutated EGFR-IN-3 inhibits EGFR through an allosteric mechanism, biochemical IC50 values at varying ATP concentrations: 10 µM, 10.0 µM, 100.0 µM, 1000.0 µM are 15 nM, 8.3nM,11.0 nM and 8.3 nM, respectively for L858R/T790M cells[1]. Mutated EGFR-IN-3 exhibits antiproliferative activities of a panel of EGFR allosteric inhibitors are 7.0 µM, 3.3 µM, 3.8 µM, 4.0 µM and 4.5 µM for parental, WT, L858R, L858R/T790M and L858R/T790M/C797S, respectively in the absence of Cetuximab in Ba/F3 cells[1]. Mutated EGFR-IN-3 exhibits antiproliferative activities of a panel of EGFR allosteric inhibitors are 3.2 µM, 2.7 µM, 0.36 µM and 0.20 µM for WT,L858R, L858R/T790M and L858R/T790M/C797S, respectively in the presence of Cetuximab in Ba/F3 cells[1].

[1]. De Clercq DJH，et al. Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors.ACS Med Chem Lett. 2019 Oct 22;10(11):1549-1553.