CHZ868
目录号 : GC11652
CHZ868 是一种 II 型 JAK2 抑制剂，在 EPOR JAK2 WT Ba/F3 细胞中的 IC50 为 0.17 μM。
Cas No.:1895895-38-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
CRLF2-rearranged human B-ALL cells MHH-CALL4, JAK2V617F SET2 cells, MPLW515L mutant cells |
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Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.25-1 μM |
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Applications |
In CRLF2-rearranged human B-ALL cells MHH-CALL4, CHZ868 potently inhibited JAK2 phosphorylation and cell growth. In JAK2V617F SET2 cells, CHZ868 (0.25-1 μM) potently inhibited constitutive JAK2 and STAT5 phosphorylation, and inhibited cell proliferation with GI50 of 59 nM. In MPLW515L mutant cells, CHZ868 potently inhibited cell proliferation and abrogated phosphorylation of Y1007/Y1008 in the JAK2 activation loop. In type I JAK inhibitor-persistent cells, CHZ868 dose-dependently inhibited JAK2 phosphorylation and proliferation of JAK2V617F or MPLW515L cells. |
| Animal experiment [1]: | |
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Animal models |
Jak2V617F conditional knock-in mice |
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Dosage form |
30-40 mg/kg orally once daily |
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Application |
CHZ868 normalized spleen and liver weights, demonstrating marked inhibition of extramedullary hematopoiesis. CHZ868 therapy reduced the bone marrow megakaryocytic hyperplasia. In a murine model of PMF-like disease, CHZ868 (40 mg/kg) therapy significantly improved survival of mice with MPLW515L-induced myelofibrosis and dose-dependently reduced hepatomegaly and normalized spleen weight and size. CHZ868 therapy markedly decreased bone marrow and spleen reticulin fibrosis. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Meyer S C, Keller M D, Chiu S, et al. CHZ868, a type II JAK2 inhibitor, reverses type I JAK inhibitor persistence and demonstrates efficacy in myeloproliferative neoplasms[J]. Cancer cell, 2015, 28(1): 15-28. | |
CHZ868 is a type II JAK2 inhibitor with IC50 value of 110 nM [1].
JAK2 (Janus kinase 2) is a non-receptor tyrosine kinase. Mutations in JAK2 is associated with many myeloproliferative disorders.
In CRLF2-rearranged human B-ALL cells MHH-CALL4, CHZ868 potently inhibited JAK2 phosphorylation and cell growth [1]. CHZ868 is a type II JAK2 inhibitor. In JAK2V617F SET2 cells, CHZ868 potently inhibited constitutive JAK2 and STAT5 phosphorylation, and inhibited cell proliferation with GI50 value of 59 nM. In MPLW515L mutant cells, CHZ868 potently inhibited cell proliferation and abrogated phosphorylation of Y1007/Y1008 in the JAK2 activation loop. In type I JAK inhibitor-persistent cells, CHZ868 potently and concentration-dependently inhibited JAK2 phosphorylation and proliferation of JAK2V617F or MPLW515L cells [2].
In mice with human or murine B-ALL, CHZ868 improved survival. In JAK2-dependent B-ALL mice, CHZ868 and dexamethasone synergistically induced apoptosis and improved survival compared to CHZ868 alone [1]. In Jak2V617F-driven polycythemiavera (PV), CHZ868 (30 - 40 mg/kg orally once daily) inhibited JAK-STAT signaling and significantly reduced the proportion of mutant cells in the bone marrow. In MPLW515L-induced myelofibrosis (MF), CHZ868 completely inhibited STAT3 and STAT5 phosphorylation, and reduced JAK2 phosphorylation. CHZ868 also improved survival and reduced hepatomegaly in a dose-dependent way [2].
References:
[1]. Wu SC, Li LS, Kopp N, et al. Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell, 2015, 28(1): 29-41.
[2]. Meyer SC, Keller MD, Chiu S, et al. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. Cancer Cell, 2015, 28(1): 15-28.
| Cas No. | 1895895-38-1 | SDF | |
| 化学名 | N-(4-((2-((2,4-difluorophenyl)amino)-1,4-dimethyl-1H-benzo[d]imidazol-5-yl)oxy)pyridin-2-yl)acetamide | ||
| Canonical SMILES | CN(C(NC1=CC=C(F)C=C1F)=N2)C(C2=C3C)=CC=C3OC4=CC=NC(NC(C)=O)=C4 | ||
| 分子式 | C22H19F2N5O2 | 分子量 | 423.42 |
| 溶解度 | Soluble in DMSO | 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 | 2.3617 mL | 11.8086 mL | 23.6172 mL |
| 5 mM | 0.4723 mL | 2.3617 mL | 4.7234 mL |
| 10 mM | 0.2362 mL | 1.1809 mL | 2.3617 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。