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Gilteritinib

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Chemical Structure| 1254053-43-4 同义名 : 吉瑞替尼 ;ASP2215
CAS号 : 1254053-43-4
货号 : A425350
分子式 : C29H44N8O3
纯度 : 99%+
分子量 : 552.712
MDL号 : MFCD28144685
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 2 mg/mL(3.62 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 100 mg/mL(180.93 mM)，配合低频超声，并调节pH至2，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：
生物活性
靶点

  • FLT3

    FLT3, IC50:0.29 nM
描述 Gilteritinib (ASP2215) effectively inhibits FLT3, leukocyte tyrosine kinase (LTK), anaplastic lymphoma kinase (ALK), and AXL kinases in 78 tested tyrosine kinases, achieving over 50% inhibition at 1 nM. Its IC50 for FLT3 is exceptionally low at 0.29 nM, making it roughly 800 times more potent against FLT3 than c-KIT[1]. Gilteritinib inhibits the activity of 8 of the 78 tested kinases by >50% at concentrations of 1 nM (Flt3, LTK, ALK, and Ax1) or 5 nM (TrkA, ROS, RET, and Mer). Its IC50s are 0.29 nM and 0.73 nM, respectively. Gilteritinib inhibits Flt3 with an IC50 approximately 800-fold higher than the concentration required to inhibit c-kit (230 NM). The antiproliferative activity of Gilteritinib is evaluated by MV4-11 and MOLM-13 cells endogenously expressing Flt3-ITD. After 5 days of treatment, the IC50 of gitlitinib for MV4-11 and MOLM-13 cells is 0.92 nM (95%CI: 0.23-3.6 nM) and 2.9 nM (95%CI: 1.4-5.8 nM), respectively. Growth inhibition of MV4-11 cells is accompanied by inhibition of Flt3 phosphorylation. The phosphorylation levels of Flt3 were 57%, 8%, and 1% after 2 h of Gilteritinib at 0.1 nM, 1 nM, and 10 nM compared to vehicle controls, respectively. In addition, doses as low as 0.1 nM or 1 nM inhibit phosphorylated ERK, STAT5, and AKT, all of which are downstream targets for Flt3 activation. To investigate the effect of Gilteritinib on Ax1 inhibition, MV4-11 cells expressing exogenous Ax1 are treated with Gilteritinib. Gilteritinib treatment reduces phosphorylated Axl levels by 38%, 29%, and 22%, respectively, at 4 h at concentrations of 1 nM, 10 nM, and 100 nM[2].
作用机制 Gilteritinib binds to FLT3 at the ATP-binding site.[2]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.81mL

0.36mL

0.18mL

9.05mL

1.81mL

0.90mL

18.09mL

3.62mL

1.81mL
参考文献

[1]ASP2215, a novel FLT3/AXL inhibitor: Preclinical evaluation in acute myeloid leukemia (AML). 2014 ASCO Annual Meeting.

[2]Mori M, et al. Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Invest New Drugs. 2017 Oct;35(5):556-565.