Naquotinib (mesylate)

Naquotinib mesylate (ASP8273 mesylate) is an orally available, mutant-selective and irreversible EGFR inhibitor; with IC₅₀s of 8-33 nM toward EGFR mutants and 230 nM for EGFR. IC50 & Target: IC50: 230 nM (EGFR); 8-33 (EGFR mutants)^[1] In Vitro: In assays using endogenously EGFR-dependent cells, Naquotinib inhibits the growth of PC-9(del ex19), HCC827(del ex19), NCI-H1975(del ex19/T790M) and PC-9ER(del ex19/T790M) with IC₅₀s of 8-33 nM^[1]. Naquotinib selectively inhibits phosphorylation of EGFR and its down-stream signal pathway, ERK and Akt from 10nM in HCC827 and NCI-H1975 while inhibitory effects are only detected at 1000nM in A431.In NCI-H1650 (del ex19), Naquotinib inhibits cell growth with an IC₅₀ value of 70nM while other EGFR-TKIs are only partially effective^[2]. In Vivo: Oral Naquotinib treatment dose dependently induces tumor regression in NCI-H1975 (L858R/T790M), HCC827 (del ex19) and PC-9 (del ex19) xenograft models. Dosing schedules does not affect the efficacy of Naquotinib. In an NCI-H1975 xenograft model, complete regression of tumor is achieved after 14-days of Naquotinib treatment. Complete regression is maintained in 50% of mice more than 85 days after cessation of Naquotinib treatment^[2].