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nM),并且在NK-92 JAK3\u002FJAK1异二聚体测定(942 nM)中具有所需的阈值选择性[1]。",{"key":230,"value":231},"体内研究","Gandotinib(LY2784544)有效抑制Ba\u002FF3-JAK2V617F-GFP(绿色荧光蛋白)腹水肿瘤细胞(TED50 = 12.7 mg\u002Fkg)中的STAT5磷酸化,并显着降低(P \u003C0.05)Ba\u002FF3-JAK2V617F-GFP肿瘤负荷。 JAK2V617F诱导的MPN模型(TED50 = 13.7 mg\u002Fkg,每日两次)[1]。",{"key":233,"value":234},"细胞实验","将表达JAK2V617F的Ba \u002F F3细胞置于含RPMI-1640的载体（DMSO）或Gandotinib（LY2784544）（浓度范围0.001-20μM）（1×104细胞\u002F 96孔）中。除了添加IL-3（2ng \u002F mL）之外，类似地处理表达野生型JAK2的Ba \u002F F3细胞。孵育72小时后，通过加入Cell Titer 96 Aqueous One Solution Reagent（20μL\u002F孔）评估细胞增殖。使用GraphPad Prism 4软件[1]计算抑制细胞增殖的IC 50。",{"key":236,"value":237},"动物实验","小鼠[1]通过测量小鼠腹水肿瘤模型中STAT5磷酸化的抑制来评估JAK2V617F信号传导的剂量和时间依赖性体内抑制。将Ba \u002F F3-JAK2V617F-GFP细胞（1×107）植入严重联合免疫缺陷小鼠（SCID小鼠）的腹腔内，并使其发展成腹水肿瘤7天。对于剂量反应研究（6只动物\u002F组），Gandotinib（LY2784544）通过口服强饲法（2.5,5,10,20,40或80 mg \u002F kg）给药一次，然后30分钟后收集腹水肿瘤细胞固定，用Mouse-anti-pSTAT5（pY694）Alexa Fluor 647（1:10稀释）孵育2小时，并通过流式细胞术分析。时间过程研究类似地进行，除了动物用20,40或80mg \u002F kg的Gandotinib（LY2784544）治疗，并且在给药后以0.25-6h的预定间隔收集腹水肿瘤细胞。通过单因素方差分析和Dunnett检验（α= 0.05）分析数据。使用四参数逻辑曲线拟合程序分析剂量响应数据。",{"key":239,"value":240},"参考文献","[1].\nMa L, et al. 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