CYT387
(Synonyms: 莫洛替尼,Cyt-387,MOMELOTINIB,CYT 387,CYT 11387) 目录号 : GC17050
A potent inhibitor of JAK1 and JAK2
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 | |
| 别名 | 莫洛替尼,Cyt-387,MOMELOTINIB,CYT 387,CYT 11387 | ||
| 化学名 | 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 | ||
| 分子式 | C23H22N6O2 | 分子量 | 414.46 |
| 溶解度 | ≥ 20.7 mg/mL 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 | 2.4128 mL | 12.0639 mL | 24.1278 mL |
| 5 mM | 0.4826 mL | 2.4128 mL | 4.8256 mL |
| 10 mM | 0.2413 mL | 1.2064 mL | 2.4128 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet