CHZ868 |
| Katalog-Nr.GC11652 |
CHZ868 ist ein Typ II JAK2-Inhibitor mit einem IC50 von 0,17 μM in EPOR JAK2 WT Ba/F3-Zelle.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1895895-38-1
Sample solution is provided at 25 µL, 10mM.
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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.
| 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. | |
| Cas No. | 1895895-38-1 | SDF | |
| Chemical Name | 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 | ||
| Formula | C22H19F2N5O2 | M.Wt | 423.42 |
| Löslichkeit | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 15 reference(s) in Google Scholar.)
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