CYT387 (Synonyms: Momelotinib) |
Catalog No.GC17050
One-Click Copy Product Info
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A potent inhibitor of JAK1 and JAK2
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1056634-68-4
Sample solution is provided at 25 µL, 10mM.
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CYT387, an aminopyrimidine derivative discovered by high-throughput enzyme and cell-based screening along with the optimization using structure-guided medicinal chemistry, is a potent and selective inhibitor of janus kinase 1 (JAK1), janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) with values of 50% inhibition concentration IC50 of 11 nM, 18 nM, 155 nM and 17 nM respectively. Recent studies have revealed that CYT387, at low nanomolar concentrations ranging between 500 and 1500 nM, is able to inhibit JAK2 signaling pathway, suppress proliferation and induce apoptosis in JAK2-dependent hematopoietic cell lines with non-hematopoietic cell lines intact.
Reference
[1].Tyner JW, Bumm TG, Deininger J, Wood L, Aichberger KJ, Loriaux MM, Druker BJ, Burns CJ, Fantino E, Deininger MW. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood. 2010;115(25):5232-5240.
| Kinase experiment [1]: | |
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Inhibitory activities |
Glutathione S-transferase (GST)-tagged JAK kinase domains were cloned in gateway baculovirus vectors and expressed in SF9 insect cells. The fusion proteins were purified and used in a peptide substrate phosphorylation assay. Assays were performed in 384-well Optiplates using an Alphascreen Protein Tyrosine Kinase P100 detection kit and a PerkinElmer Fusion Alpha instrument. |
| Cell experiment [1]: | |
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Cell lines |
Hematopoietic lines with JAK2V617F mutation; HEL cells with naturally acquired JAK2V617F; Baf3-EpoR-JAK2V617F cells. |
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Preparation method |
Soluble in DMSO > 10 mM. 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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Reaction Conditions |
0.1-5 μM; 3 days. |
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Applications |
In hematopoietic and somatic cell lines, CYT387 selectively inhibits JAK2-dependent cell growth and induces apoptosis. In Baf3-EpoR-JAK2V617F cells, CYT387 significantly inhibits cell growth and the phosphorylation of JAK2, extracellular signal-regulated kinase 1/2 (ERK1/2) and STAT5. |
| Animal experiment [1]: | |
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Animal models |
Mice with bone marrow transplantation. |
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Dosage form |
25, 50 mg/kg; twice daily at 10- to 12-hour intervals from day 34 after bone marrow transplantation to day 82; administrated orally. |
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Preparation method |
Dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone). Subsequently, the CYT387/NMP mix was diluted with 0.14M Captisol to a concentration of 6 mg/mL and further diluted with 0.1M Captisol to a final concentration of 4 mg/mL. |
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Applications |
In Balb/c mice transplanted with bone marrow transduced with a JAK2V617F retrovirus, CYT387 reduces white cell counts and hematocrit. Also, CYT387 decreases granulocyte population and increases lymphocyte cell population. No change in body weight in CYT387-treated mice. CYT387 significantly reduces spleen size in both the 25 mg/kg and 50 mg/kg groups. |
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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]. Tyner JW, Bumm TG, Deininger J, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25): 5232-5240. | |
| Cas No. | 1056634-68-4 | SDF | |
| Synonyms | Momelotinib | ||
| Chemical Name | N-(cyanomethyl)-4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]benzamide | ||
| Canonical SMILES | C1COCCN1C2=CC=C(C=C2)NC3=NC=CC(=N3)C4=CC=C(C=C4)C(=O)NCC#N | ||
| Formula | C23H22N6O2 | M.Wt | 414.46 |
| Solubility | ≥ 20.7 mg/mL 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 | 2.4128 mL | 12.0639 mL | 24.1278 mL |
| 5 mM | 482.6 μL | 2.4128 mL | 4.8256 mL |
| 10 mM | 241.3 μL | 1.2064 mL | 2.4128 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 saline, 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: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)