Gilteritinib

TYK1/LTK:0.35 nM|FLT3:0.29 nM|c-Kit:230 nM|Axl:0.73 nM|EML4-ALK:1.2 nM

方法：为测试体内抗肿瘤活性，将 Gilteritinib (1-10 mg/kg) 口服给药给携带人急性髓细胞白血病肿瘤 MV4-11 的 Nude 小鼠，每天一次，持续二十八天。 结果：在 1 mg/kg/天 (63%)和 3 mg/kg/天 (80%) 剂量下观察到 MV4-11 肿瘤的显着生长抑制。并且在 6 mg/kg/天 (93%) 和 10 mg/kg/天 (100%) 剂量下观察到肿瘤几乎完全消退。[1]

方法：人急性髓细胞白血病细胞 MV4-11 和 MOLM-13 用 Gilteritinib (0.01-100 nM) 处理 5 天，使用 CellTiter-Glo 检测细胞增殖。 结果：Gilteritinib 抑制 MV4-11 和 MOLM-13 细胞的生长，平均 IC50 值分别为 0.92 nM 和 2.9 nM。[1] 方法：人急性髓细胞白血病细胞 Molm14 用 Gilteritinib (5-20 nM) 处理 1-24 h，使用 Western Blot 检测靶点蛋白表达水平。 结果：当与 Molm14 细胞孵育 1 h 时，Gilteritinib 有效地抑制了 FLT3 及其下游信号通路的活性。但是到 24? h，尽管 FLT3 持续受到抑制，但 ERK 信号传导反弹，如 pERK 上调。[2]

DMSO:1 mg/mL (1.81 mM); Ethanol:4 mg/mL (7.24 mM); H2O:Insoluble;

Gilteritinib is dissolved in DMSO and stored, and then diluted with appropriate media before use.The effect of Gilteritinib on MV4-11 and MOLM-13 cells is assessed using the CellTiter-Glo Luminescent Cell Viability Assay. Subsequent studies are conducted to examine the effect of Gilteritinib and Quizartinib on Ba/F3 cells expressing either FLT3-ITD, FLT3-D835Y, FLT3-ITD-D835Y, FLT3-ITD-F691 L, or FLT3-ITD-F691I. MV4-11 and MOLM-13 cells are treated with DMSO or increasing concentrations of Gilteritinib (0.01, 0.1, 1, 10, and 100 nM) for 5 days, and cell viability is measured using CellTiter-Glo

MiceAntitumor activity is evaluated in nude mice transplanted with MV4-11 AML cells. The pharmacokinetics in xenografted mice is also investigated. MV4-11 xenografted-mice are treated with oral administration of Gilteritinib at 10 mg/kg for 4 days. Treatment of Gilteritinib for 28 days results in dose-dependent inhibition of MV4-11 tumor growth and induces complete tumor regression at more than 6 mg/kg