WZ4002 is a novel mutant-selective epidermal growth factor receptor (EGFR) kinase inhibitor that potently and irreversibly suppresses the ATP-dependent auto-phosphorylation of both wild-type EGFR and EGFR mutants, including EGFR delE746_A750/T790M, EGFR L858R/T790M, EGFR T790M, EGFR delE746_A750 and EGFR L858R, with inhibition constant Ki of 13.6 nM, 1.8 nM, 4 nM, 5 nM, 3.9 nM and 8.5 nM respectively. Although WZ4002 is actively against EGFR mutants rather than wild-type EGFR at lower concentrations resulting in less toxicity in normal tissues, wild-type EGFR is susceptible to higher concentrations of WZ4002 as well as prolonged administration of WZ4002, especially in tissues where it accumulates.
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