AST-1306

AST-1306 is a novel irreversible inhibitor of EGFR and ErbB2 with IC50 of 0.5 nM and 3 nM, also effective in mutation EGFR T790M/L858R, more potent to ErbB2-overexpressing cells, 3000-fold selective for ErbB family than other kinases, (In Vitro) :AST1306 tosylate (AST-1306 (TsOH) ; 0.19-6.25 μM; 72 hours) induces a significant, concentration-dependent inhibition of the growth of HIH3T3-EGFR T790M/L858R cells.AST1306 tosylate inhibits the activation of tyrosine kinases and downstream signaling pathways in A549 cells, Calu-3 cells and SK-OV-3 cells. AST1306 tosylate dose-dependently and markedly inhibits EGF-induced EGFR phosphorylation in A549 cells.AST1306 tosylate (0.1, 0.5, 1.0, 5.0 μM) can dramatically inhibit the growth of both tumor cells on soft agar, and SK-OV-3 cells exhibited much more sensitivity than that of A549 cells.AST1306 tosylate (0.001-1.0 μM; 4 hours) is more than 3000-fold selective for ErbB family kinases over other kinase families.AST1306 tosylate potently inhibits the EGFR T790M/L858R double mutant, exhibiting an IC50 value of 12±2 nmol/L. (In Vivo) :AST1306 tosylate (AST-1306 (TsOH) ; p.o.; 25-100 mg/kg; twice daily; for 28 days) causes a dramatic suppression of tumor growth in SK-OV-3 and Calu-3 xenograft models.