Gilteritinib hemifumarate
(Synonyms: ASP2215 hemifumarate) 目录号 : GC36135
A FLT3 inhibitor
Cas No.:1254053-84-3
Sample solution is provided at 25 µL, 10mM.
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Gilteritinib is an inhibitor of FMS-related tyrosine kinase 3 (FLT3; IC50 = 5 nM for the wild-type enzyme).1 It inhibits mutant forms of FLT3, including FLT3 with the internal tandem duplication mutation (FLT3-ITD), FLT3-ITD expressing the F691L mutation, and FLT3 with various tyrosine kinase domain mutations (FLT3-TKD; IC50s =1.4-1.8, 12.2, and 0.7-2 nM, respectively). Gilteritinib also inhibits Axl and c-Kit with IC50 values of 41 and 102 nM, respectively. It decreases the viability of blast cells isolated from patients with relapsed acute myeloid leukemia (AML) in a concentration-dependent manner. Formulations containing gilteritinib have been used in the treatment of AML.
1.Lee, L.Y., Hernandez, D., Rajkhowa, T., et al.Preclinical studies of gilteritinib, a next-generation FLT3 inhibitorBlood129(2)257-260(2017)
Kinase experiment: | The kinase inhibitory activity of Gilteritinib is tested against a panel of 78 tested kinases using ATP concentrations that are approximately equal to the Km value for each kinase in a TK-ELISA or off-chip mobility shift assay. Initially, two concentrations of Gilteritinib (1 nM and 5 nM) are tested to assess each compound’s inhibitory effect on TK activity. Further studies are then conducted using a dose range of Gilteritinib to determine IC50 values for kinases in which activity is inhibited by >50% with 1 nM Gilteritinib as well as for c-KIT. TK-ELISA and MSA assays are used to conduct IC50 studies for FLT3, LTK, AXL, and c-KIT; the HTRF KinEASE-TK assay is performed to assess the IC50 value of echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)[2]. |
Cell experiment: | 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[2]. |
Animal experiment: | Mice[1]Antitumor 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[1]. |
References: [1]. ASP2215, a novel FLT3/AXL inhibitor: Preclinical evaluation in acute myeloid leukemia (AML). 2014 ASCO Annual Meeting. | |
| Cas No. | 1254053-84-3 | SDF | |
| 别名 | ASP2215 hemifumarate | ||
| Canonical SMILES | OC(/C=C/C(O)=O)=O.NC(C1=NC(CC)=C(NC2CCOCC2)N=C1NC3=CC(OC)=C(N4CCC(N5CCN(C)CC5)CC4)C=C3)=O.[0.5] | ||
| 分子式 | C29H44N8O3 0.5C4H4O4 | 分子量 | 610.75 |
| 溶解度 | Water: 2 mg/mL (3.27 mM); DMSO: 1.74 mg/mL (2.85 mM and warming) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6373 mL | 8.1867 mL | 16.3733 mL |
| 5 mM | 0.3275 mL | 1.6373 mL | 3.2747 mL |
| 10 mM | 0.1637 mL | 0.8187 mL | 1.6373 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet