DS-1205b free base is a potent and selective inhibitor of AXL kinase , with an IC 50 of 1.3 nM. DS-1205b free base also inhibits MER , MET , and TRKA , with IC 50 s of 63, 104, and 407 nM, respectively. DS-1205b free base can inhibit cell migration in vitro and tumor growth in vivo
In Vitro
DS-1205b (0.3-33 μM; 2-24 h) inhibits hGAS6-induced migration in NIH3T3-AXL cells (EC 50 =2.7 nM). DS-1205b (1-10000 μM; 2-24 h) significantly inhibits the phosphorylation of AXL in NIH3T3-AXL cells. DS-1205b decreases NIH3T3 cell proliferation but not obviously inhibits growth (GI 50 >10,000 nM). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: NIH3T3-AXL cells Concentration: 1, 10, 100, 1000, 10000 μM Incubation Time: 2, 24 hours Result: Completely inhibited the phosphorylation of AXL at concentrations above 10 nM. Slightly inhibited the phosphorylation of AKT serine/threonine kinase in a dose-dependent manner.
In Vivo
DS-1205b (3.1-50 mg/kg; p.o. bid for 5 d) exhibits pAXL inhibition mediated antitumor effects in mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female NOD/Shi-scid IL-2Rγ KO Jic mice were implanted with NIH3T3-AXL tumor blocks Dosage: 3.1, 6.3, 13, 25, 50 mg/kg Administration: P.o. twice daily for 5 days Result: Inhibited tumor growth by 39-94%. Reduced the phosphorylation of both AXL and AKT in tumors.
