Nazartinib mesylate (EGF81)

Description: Nazartinib mesylate (formerly known as EGF816 mesylate and NVS-816 mesylate) is a novel, covalent/irreversible, and mutant-selective EGFR inhibitor with Ki and Kinact of 31 nM and 0.222 min?1 on EGFR(L858R/790M) mutant, respectively. Nazartinib specifically targets EGFR-activating mutations arising de novo and upon resistance acquisition, while sparing wild-type (WT) EGFR. Non-small cell lung cancer patients carrying oncogenic EGFR mutations initially respond to EGFR-targeted therapy, but later elicit minimal response due to dose-limiting toxicities and acquired resistance.Nazartinib potently inhibits the most common EGFR mutations L858R, Ex19del, and T790M in vitro. The cellular activity of EGF816 on EGFR mutants are assessed using three well-characterized cell lines, H3255, HCC827, and H1975, which harbor the L858R, Ex19del, and L858R/T790M mutations, respectively. Nazartinib is currently under clinical evaluation (phase I/II clinical trials) in patients harboring EGFR mutations, including T790M.

References: Cancer Res. 2016 Mar 15; 76(6):1591-602; J Med Chem. 2016 Jul 28; 59(14):6671-89.

Related CAS#:1508250-71-2 (free); 1508256-20-9 (S-enantiomer); 1508250-72-3 (mesylate)