Fig. 3: Biochemical evaluation of inhibition synergy.
From: Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors
a Inhibition synergy analysis using purified EGFR kinase domain. Compound combinations were dispensed using a digital drug dispenser and IC50s of one inhibitor were plotted as a function of the concentration of the other inhibitor. Similar to the FP binding experiments, osimertinib, AZ5104, and naquotinib enhanced the potency of JBJ-125, and vice versa. Mavelertinib was neither synergistic nor antagonistic with regard to JBJ-125 potency. Reported as mean ± SD (n = 3 independent experiments). b Labeling by osimertinib or mavelertinib in the presence or absence of allosteric inhibitor. Percent labeling was assessed via intact mass spectrometry. Reported as mean (n = 2 independent experiments). c Synergy evaluation with EGFR(L858R/C797S) and the osimertinib+JBJ−125 combination. The allosteric inhibitor enhances the potency of osimertinib despite the C797S mutation. Reported as mean ± SD (n = 3 independent experiments). Source data are provided as a Source Data file.
