The HER family of receptor tyrosine kinases, EGFR, HER2, HER3, and HER4, mediate proliferation, migration, adhesion, differentiation, and survival in many different cell types and have been implicated in the development and progression of a variety of human tumors. Canertinib is an irreversible quinazoline-based HER family tyrosine kinase inhibitor with IC50 values of 0.8, 19, and 7 nM for blocking in vitro activity of EGFR, HER2, and HER4, respectively. As a broadly applicable anti-cancer agent, it has been used to suppress proliferation of malignant peripheral nerve sheath tumor cells (effective concentration of 250-500 nM), to inhibit growth and induce dose-dependent apoptosis in a panel of neuroblastoma cell lines (IC50s = 0.94-2.45 μM), and to reduce proliferation of acute myeloid leukemia cells (IC50 = 0.27 μM). Canertinib also displays anti-neoplastic activity towards T98G glioblastoma cells, HCT8 colorectal carcinoma cells, and cells expressing the breast cancer resistance protein.
