Avitinib (maleate)

Avitinib (Abivertinib) maleate is a third-generation, irreversible and orally active selective EGFR inhibitor, with IC₅₀ values of 0.18 nM, 0.18 nM, 7.68 nM and against EGFR L858R, EGFR T790M and wild-type EGFR. Avitinib maleate is also a BTK inhibitor that induces apoptosis and inhibits phosphorylation of BTK in mantle cell lymphoma. Avitinib maleate shows anticancer effects^[1][2]. IC50 & Target:IC50: 7.68 nM (wild-type EGFR)^[1] In Vitro:Avitinib (AC0010; 0.13 nM-2 μM; 2 h) maleate selectively inhibits mutant EGFR phosphorylation with IC₅₀ values of 7.3 and 2.8 nM in NCI-H1975 and NIH/3T3_TC32T8 cells, about 115- and 298-fold more sensitive than that of the inhibition of wild-type EGFR in A431. Avitinib potently inhibits EGFR-Tyr1068 phosphorylation in NCI-H1975 cells, and the selectivity ratio is at 65-fold for NCI-H1975 cells versus A431 cells. In addition to inhibition of EGFR-Tyr1068 phosphorylation, Avitinib inhibits phosphorylation of the downstream targets Akt and ERK1/2 in NCI-H1975 and HCC827 cells^[1]. In Vivo:Avitinib (AC0010; 12.5-500 mg/kg; orally administration; once daily; for 14 days) maleate inhibits EGFR-mutant tumor growth but not wild-type EGFR tumor growth in xenograft models over extended duration^[1].