To address this issue, the irreversible EGFR TKIs (afatinib, osimertinib, WZ4002, and CO-1686) which contain a Michael acceptor moiety for binding covalently to the thiol group of Cys797 in the ATP binding domain of EGFR, were developed to treat NSCLC via the efficient inhibition of EGFR mutants (Figure 1; Castellanos and Horn, 2015). Here, EGFR is linked to non-small cell lung carcinoma.