Osimertinib’s mechanism of action

Osimertinib (Osimertinib) is an epidermal growth factor receptor (EGFR) kinase inhibitor that irreversibly binds to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at concentrations approximately nine-fold lower than wild type. Following oral administration of osimertinib, two pharmacologically active metabolites with inhibitory properties similar to those of osimertinib were found in plasma (AZ7550 and AZ5104, circulating in approximately 10% of the parent). AZ7550 showed similar potency to osimertinib, whereas AZ5104 showed stronger potency against exon 19 deletion and T790M mutant (approximately 8-fold) and wild-type (approximately 15-fold) EGFR.