Therapeutics: Epidermal growth factor receptor (EGFR)

Cell culture and mouse studies identified an inhibitor of mutant EGFR that could help treat lung cancer. Chemical screening of a compound library in a protein expression assay and optimization of hits identified an allosteric EGFR inhibitor that bound the L858R and T790M EGFR mutants with IC50 values of 9 and 600 nM, respectively, and bound EGFR harboring both mutations with an IC50 of 3 nM. In a mouse model of EGFR-mutant lung cancer, the allosteric inhibitor plus cetuximab decreased tumor growth compared with either agent alone. In mice, the allosteric inhibitor had a half-life of two hours and an oral bioavailability of 26%. Next steps could include optimizing and testing the inhibitor in other models of lung cancer...