CGP 57380

MNK1 (IC50 = 2.2 μM)

CGP57380 在细胞测定中抑制 eIF4E 磷酸化，IC50 约为 3 μM。使用 CGP57380 去磷酸化 eIF4E 会导致 293 细胞表达更多帽依赖性报告基因。 [1] CGP57380 以剂量依赖性方式抑制蛋白质合成、VSMC 肥大和 Ang II 刺激的 eIF4E 磷酸化。 [2]在小鼠胚胎成纤维细胞 (MEF) 中，CGP57380 使野生型细胞更容易受到血清撤除引起的细胞凋亡的影响。 [3] CGP57380 阻止 BC 祖细胞重复复制。[4]

CGP57380 (40 mg/kg/d ip) 可有效消除 BC CML 细胞作为 LSC 和连续移植免疫缺陷小鼠的功能。 [4]

CGP 57380 是 MNK1 的有效抑制剂，IC50 值为 2.2 μM。

重组 p38 同种型在以下条件下被 Mkk6(E) 激活：p38 (100 ng/mL)、Mkk6(E) (30 ng/mL)、ATP (100 mM) 在激酶缓冲液（25 mM Hepes、25 mM b-甘油磷酸盐、0.1 mM 原钒酸钠、25 mM MgCl2、2.5 mM DTT，pH 7.4）并在 30°C 下孵育 30 分钟。 Mnk1 (2 ng/mL)、HA-eIF4E (10 ng/mL) 和 ATP (300 mM) 是 Mnk1 活性的典型检测反应的主要成分。添加活化的 p38 (0.03–3 ng/mL) 启动反应，30 分钟后在 30°C 下添加 SDS 上样缓冲液终止反应。使用相同的测定条件来鉴定 Mnk1 抑制剂，但在暴露于底物和抑制剂之前，首先使用活性 p38a 预激活 Mnk1。

CD34+ cells (5×105) or GMPs (1×105) are resuspended in 25 μL 1% FBS/PBS solution and injected into the right femur of 8- to 10-wk-old sublethally irradiated (200 cGy) female mice (n=5 mice per group). For each experiment, 1% FBS/PBS solution-injected mice serve as the sham control. Using flow cytometry, mice are examined every 4 weeks after the transplant to see if human cells have grafted. Engrafted mice are treated for 3 weeks with CGP57380 (40 mg/kg/d) intraperitoneally, dasatinib (5 mg/kg/d) by gavage, or vehicle alone (n = 5 mice per group) after 6 weeks following transplantation. After the course of treatment is complete, mice are put down, and CD45+ cells are extracted from the BM and spleen using anti-human CD45-specific immunomagnetic microbeads. In the colony forming cell (CFC) assay, an aliquot of 1×105 human CD45+ cells is seeded into methylcellulose, and colonies are counted after 2 weeks. The remaining human cells from each primary transplant recipient are then all intrafemorally injected into secondary recipients, and human engraftment is monitored every two weeks starting at four weeks. All mice are put to death after 16 weeks. RT-PCR is used to find BCR-ABL1 transcripts, and flow cytometry is used to evaluate engraftment in BM and blood.

[1]. Mol Cell Biol . 2001 Aug;21(16):5500-11.

[2]. Circ Res . 2003 Dec 12;93(12):1218-24.

[3]. Genes Cells . 2007 Oct;12(10):1133-40.

[1]. Proc Natl Acad Sci U S A . 2013 Jun 18;110(25):E2298-307.

C11H9FN6

244.23

244.09

C, 54.10; H, 3.71; F, 7.78; N, 34.41

522629-08-9

Solid powder

C1=CC(=CC=C1NC2=C3C(=NC=NC3=NN2)N)F

UQPMANVRZYYQMD-UHFFFAOYSA-N

InChI=1S/C11H9FN6/c12-6-1-3-7(4-2-6)16-11-8-9(13)14-5-15-10(8)17-18-11/h1-5H,(H4,13,14,15,16,17,18)

3-N-(4-fluorophenyl)-2H-pyrazolo[3,4-d]pyrimidine-3,4-diamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 4% DMSO +30%PEG 300 +ddH2O: 10mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。