The HER family of receptor tyrosine kinases, EGFR, HER-2, HER-3, and HER-4, 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.
|
