WP1066
(Synonyms: (2E)-3-(6-溴-2-吡啶基)-2-氰基-N-[(1S)-1-苯基乙基]-2-丙烯酰胺) 目录号 : GC15980
An inhibitor of STAT3
Cas No.:857064-38-1
Sample solution is provided at 25 µL, 10mM.
WP1066, an analogue of AG490, is a novel and potent inhibitor of janus kinase 2 (JAK2), which inhibits the phosphorylation of JAK2 and degrades JAK2 protein consequently blocking JAK2’s downstream signal transducer and activator of transcription (transcription-3 and transcription-5) as well as phosphoinositide-3-kinase pathways in a dose- and time-dependent manner. Results of preliminary studies suggest that WP1066 inhibits the growth of xenograft tumors generated from Caki-1 renal carcinoma cells (RCC) suppressing tumor angiogenesis and exhibits antiproliferative activity in AML colony-forming cells from newly diagnosed AML patients as well as in AML cell lines OCIM2 and K562, which potentiates it to treat RCC, acute myeloid leukemia (AML) and other hematologic maglignancies.
Reference
[1].Srdan Verstovsek, Taghi Manshouri, Alfonso Quintas-Cardama, David Harris, Jorge Cortes, Francis J. Giles, Hagop Kantarjian, Waldemar Priebe, and Zeev Estrov. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res 2008; 14: 788-796
[2].Alessandra Ferrajoli, Stefan Faderl, Quin Van, Patricia Koch, David Harris, Zhiming Liu, Inbal Hazan-Halevy, Yongtao Wang, Hagop M. Kantarjian, Waldemar Priebe, and Zeev Estrov. WP1066 disrupts janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res 2007; 67: 11291-11299
[3].A Horiguchi, T Asano, K Kuroda, A Sato, J Asakuma, K Ito, M Hayakawa, M Sumitomo and T Asano. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. British Journal of Cancer 2010; 102: 1592-1599
| Cell experiment [1]: | |
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Cell lines |
HEL cells carrying the mutant JAK2 V617F isoform |
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Preparation method |
The solubility of this compound in DMSO is > 17.8 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0 ~ 6 μM; 72 hrs |
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Applications |
In HEL cells carrying the mutant JAK2 V617F isoform, WP1066 markedly inhibited cell growth in a dose-dependent manner, with the IC20, IC50 and IC80 values of 0.8, 2.3 and 3.8 μM, respectively. At the concentrations of 0.5, 1.0, 2.0, 3.0 and 4.0 μM, WP1066 inhibited phosphorylation of JAK2, STAT3, STAT5 as well as ERK1/2, without affecting phosphorylation of JAK1 and JAK3. |
| Animal experiment [2]: | |
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Animal models |
Nude mice bearing Caki-1 cells |
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Dosage form |
40 mg/kg; p.o.; q.d., 5 days on and 2 days off for 19 days |
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Applications |
In nude mice bearing Caki-1 cells, WP1066 significantly inhibited tumor growth. The immunohistochemical analysis results of Caki-1 xenograft tumors showed that there was little p-STAT3 immunostaining in the WP1066 treatment group which had similar total STAT3 immunostaining as the vehicle group. The results suggested that WP1066 inhibited STAT3 phosphorylation without altering STAT3 expression. |
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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]. Srdan Verstovsek, Taghi Manshouri, Alfonso Quintas-Cardama, David Harris, Jorge Cortes, Francis J. Giles, Hagop Kantarjian, Waldemar Priebe, and Zeev Estrov. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res 2008; 14: 788-796. [2]. A Horiguchi, T Asano, K Kuroda, A Sato, J Asakuma, K Ito, M Hayakawa, M Sumitomo and T Asano. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. British Journal of Cancer 2010; 102: 1592-1599. | |
| Cas No. | 857064-38-1 | SDF | |
| 别名 | (2E)-3-(6-溴-2-吡啶基)-2-氰基-N-[(1S)-1-苯基乙基]-2-丙烯酰胺 | ||
| 化学名 | (E)-3-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylethyl]prop-2-enamide | ||
| Canonical SMILES | CC(C1=CC=CC=C1)NC(=O)C(=CC2=NC(=CC=C2)Br)C#N | ||
| 分子式 | C17H14BrN3O | 分子量 | 356.22 |
| 溶解度 | ≥ 17.8 mg/mL in DMSO, ≥ 24.6 mg/mL in EtOH with ultrasonic and warming | 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 | 2.8073 mL | 14.0363 mL | 28.0725 mL |
| 5 mM | 0.5615 mL | 2.8073 mL | 5.6145 mL |
| 10 mM | 0.2807 mL | 1.4036 mL | 2.8073 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet