Nazartinib mesylate

Nazartinib mesylate (EGF816 mesylate) is a novel, covalent mutant-selective EGFR inhibitor, with K_i and K_inact of 31 nM and 0.222 min^?1 on EGFR(L858R/790M) mutant, respectively. IC50 & Target: Ki: 31 nM (EGFR(L858R/790M) mutant)^[2] In Vitro: Nazartinib (EGF816) has inhibitory effect on the mutant cell lines with IC₅₀s of 4, 6, 2 nM in H1975, H3255, and HCC827, respectively, and demonstrates improved ADME and PK properties^[1]. Nazartinib (EGF816) shows potent inhibition of pEGFR levels in H3255, HCC827, and H1975 cell lines with EC₅₀ values of 5, 1, and 3 nM, respectively. Nazartinib inhibits cell proliferation, with EC₅₀ values of 9, 11, and 25 nM in H3255, HCC827, and H1975, respectively. Nazartinib has an OC₅₀ (compound concentration at 50% occupancy) value of 2 and 5 nM on HCC827 and H1975, respectively^[2]. In Vivo: In H1975 mouse xenograft model, Nazartinib (EGF816; 50 and 20 mg/kg or 25 mg/kg, p.o.) demonstrates dose-dependent efficacy with near complete tumor cells regression at the highest dose tested (50 mg/kg)^[1]. In H1975 mouse model, Nazartinib (EGF816; 10 mg/kg, p.o.) induces tumor growth inhibition with a T/C (tumor/control volume) of 29%, and when doses are 30 and 100 mg/kg, tumor regressions are achieved (T/C, ?61% and ?80%, respectively). In the H3255 xenograft model, Nazartinib (30 mg/kg, p.o.) shows significant antitumor activity. Antiproliferative activity of Nazartinib on 89 lung cancer cell lines indicates that Nazartinib selectively inhibits cell lines containing EGFR with catalytic domain mutations^[2].