TAS-121 is an orally active, selective, covalent third-generation mutant EGFR tyrosine kinase inhibitor (EGFR-TKI). It effectively inhibits the L858R mutation (IC50=1.7 nM), Ex19del mutation (IC50=2.7 nM), L858R/T790M mutation (IC50=0.56 nM), and Ex19del/T790M mutation (IC50=1.1 nM), as well as wild-type EGFR (IC50=8.2 nM). TAS-121 also inhibits HER2 and HER4 with an IC50 of 110 nM and 2.6 nM, respectively. This compound prevents cellular proliferation by inhibiting the phosphorylation of EGFR and its downstream signaling targets, thereby inducing apoptosis. Additionally, TAS-121 demonstrates antitumor activity in xenograft models such as SW48 (EGFR G719S) and NCI-H1975 (EGFR L858R/T790M).

EGFR (WT):8.2 nM, EGFR (ex19del/T790M):1.1 nM, EGFR L858R/T790M:0.56 nM, HER2:110 nM, EGFR (ex19del):2.7 nM, EGFR L858R:1.7 nM, HER4:2.6 nM