| 生化机理 |
AST-1306 functions as an irreversible inhibitor, most likely through covalent interaction with Cys797 and Cys805 in the catalytic domains of EGFR and ErbB2, respectively. Further studies showed that AST-1306 inactivated pathways downstream of these receptors and thereby inhibited the proliferation of a panel of cancer cell lines. AST-1306 is a potent(pM) and selective inhibitor of EGFR and ErbB4 (IC50 = 500pM and 800 pM, respectively). AST-1306 blocks phosphorylation of EGFR and also prevents downstream pathways. AST-1306 also dose-dependently inhibits EGF-induced EGFR phosphorylation in the A549 cancer cell line. |
