showcasing that both inhibitors are made selective for T790M-containing EGFR through van der Waals interactions (Figure ). Additionally, versatile H-bonding methyleneamine moiety of lazertinib is distinctive potentially enabling the modest improvement in binding compared to osimertinib. Another informative comparison is the structurally-related imidazole-based covalent inhibitor LN2057 (Figure ) that forms an H-bond with K745 enabling C797S mutant inhibition at the expense of a loss of selectivity, i.e., enhanced binding to WT EGFR. By comparison, the lazertinib pyrazole substituents sterically block K745 potentially diminishing binding to WT EGFR (Figure ). The correlation of these differences in binding mode demonstrates how the pyrazole moiety of lazertinib affords distinct interactions with EGFR to enable T790M mutant selectivity.