WP1066
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
WP1066,AG490的类似物,是janus激酶2(JAK2)的一个新型有效的抑制剂。JAK2以剂量和时间依赖的方式抑制JAK2的磷酸化并降解JAK2蛋白质,从而阻断JAK2的下游信号传感器、转录(transcription-3和transcription-5)激活剂以及磷酸肌醇3激酶通路。初步研究结果表明,WP1066抑制Caki-1肾细胞癌(RCC)肿瘤模型的增长,它可抑制肿瘤血管生成在从急性髓系白血病(AML)病人分离出的AML克隆细胞中显示了抗增殖活性,同样的活性在OCIM2和K562的AML细胞株被观察到,因此也可以被用来潜在性治疗RCC、AML和其他血癌。
参考文献:
[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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 356.22 |
Cas No. | 857064-38-1 |
Formula | C17H14BrN3O |
Solubility | insoluble in H2O; ≥17.8 mg/mL in DMSO; ≥24.6 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | (E)-3-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylethyl]prop-2-enamide |
SDF | Download SDF |
Canonical SMILES | CC(C1=CC=CC=C1)NC(=O)C(=CC2=NC(=CC=C2)Br)C#N |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验 [1]: | |
细胞系 |
表达突变型JAK2 V617F亚型的HEL细胞 |
制备方法 |
在DMSO中的溶解度大于17.8 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。 |
反应条件 |
0 ~ 6 μM;72小时 |
实验结果 |
在表达突变型JAK2 V617F亚型的HEL细胞中,WP1066呈剂量依赖性地显著抑制细胞生长,其IC20值、IC50值和IC80值分别为0.8 μM、2.3 μM和3.8 μM。在0.5 μM、1.0 μM、2.0 μM、3.0 μM和4.0 μM的浓度下,WP1066抑制JAK2、STAT3、STAT5和ERK1/2磷酸化,而不影响JAK1和JAK3磷酸化。 |
动物实验 [2]: | |
动物模型 |
携带Caki-1细胞的裸小鼠 |
给药剂量 |
40 mg/kg;口服给药;每天1次,每给药5天间隔2天,持续19天 |
实验结果 |
在携带Caki-1细胞的裸小鼠中,WP1066显著抑制肿瘤生长。Caki-1异种移植瘤的免疫组化分析结果显示,WP1066治疗组几乎没有p-STAT3免疫染色。WP1066治疗组的STAT3免疫染色强度和溶剂对照组的类似。上述结果表明,WP1066抑制STAT3磷酸化,而不改变STAT3表达。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
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. |
描述 | WP1066是JAK2和STAT3的一个新型的抑制剂,在HEL细胞中对JAK2和STAT3的IC50值分别为2.30 μM和2.43 μM。 | |||||
靶点 | JAK2 | STAT3 | ||||
IC50 | 2.3 μM | 2.43 μM |
质量控制和MSDS
- 批次: