基本信息

产品描述

WP1066是一种新型JAK2和STAT3抑制剂，在HEL细胞中IC50分别为2.30 μM和2.43 μM；对JAK2，STAT3，STAT5和ERK1/2具有抑制活性，而对JAK1和JAK3没有作用。Phase 1。

靶点（IC50 & Targe）

JAK2,2.3μM

STAT3,2.43μM

体外研究

WP1066能显著抑制携带JAK2 V617F突变亚型的HEL细胞的生长，这种抑制是剂量依赖型的，它的IC20, IC50和 IC80分别是0.8, 2.3 和3.8 μM。在表达JAK2 V617F突变亚型的急性白血病HEL细胞中0.5, 1.0, 2.0, 3.0, 或 4.0 μM浓度的WP1066则可以抑制JAK2, STAT3, STAT5和ERK1/2的磷酸化，但不会抑制JAK1 和JAK3的磷酸化。[1] WP1066的浓度在0.5 到 3.0 μM之间以剂量依赖的方式抑制从病人体内获得的AML形细胞以及AML 细胞系 OCIM2和K562的增殖。在OCIM2 和K562细胞中，WP1066浓度在0.5, 1.0, 2.0, 3.0或 4.0 μM时，剂量依赖地降低JAK2 和pJAK2的蛋白水平，同时STAT3, STAT5和AKT的磷酸化水平。2 μM浓度的WP1066可以通过诱导处在细胞周期G0-G1期细胞的积累抑制OCIM2细胞增加。1, 2或 3 μM的WP1066能激活procaspase-3，裂开的PARP，剂量依赖地引起OCIM2 和K562细胞的细胞凋亡。[3] 5 μM浓度的WP1066能阻止STAT3磷酸化，2.5μM浓度时能显著抑制Caki-1和 786-O肾癌细胞的生存和增殖。5 μM WP1066还能抑制Caki-1和 786-O肾癌细胞中HIF1α 和 HIF2α的表达及VEGF的产生。[4]

体内研究

每日口服40 mg/kg剂量的WP1066，连续服用19天，能显著抑制Caki-1移植小鼠的肿瘤生长，同时磷酸化的STAT3免疫染色减少，CD34阳性 血管长度降低。 [4]

细胞实验

Cell lines: 携带JAK2 V617F突变亚型的HEL细胞系 , HL60, K562, Raji, PEER, CMK, TM 和RHN 细胞系

Concentrations: 0 - 6 μM

Incubation Time: 72 小时

Method: 利用基于MTT的细胞增殖/细胞毒性分析系统进行MTT检测。简单的说就是将对数生长期的新鲜的低密度外周血细胞核不同的细胞系用含有10% FCS的RPMI 1640洗两次，再进行血细胞计数器计数。用台盼蓝(0.1%)染色方法估算细胞的存活性。在96孔板中取相等数量的存活细胞(5 × 104 每孔)用含10% FCS的RPMI 1640培养基将体系稀释到100 μL，不加或加入依次增加浓度的WP1066，在含5% CO2的空气和37℃的培养条件下继续培养72小时。每个条件下的实验都做三组对照。之后每孔加入20 μL CellTiter96 One Solution Reagent。然后在37℃，5% CO2中继续孵育60分钟。孵育后立即用酶标仪检测490 nm波长的吸光度。

(Only for Reference)

动物实验

Animal Models: Caki-1 移植小鼠

Formulation: DMSO:聚乙二醇 300 (20:80)

Dosages: 40 mg/kg

Administration: 一天一次口服17天

(Only for Reference)

参考文献

[1] Verstovsek S, et al. Clin Cancer Res, 2008, (3), 788-796.

[2] Hatiboglu MA, et al. Int J Cancer, 2012, 131(1), 8-17

[3] Ferrajoli A, et al. Cancer Res, 2007, 67(23), 11291-11299.

[4] Horiguchi A, et al. Br J Cancer, 2010, 102(11), 1592-1599.

安全信息

图形或危害标志
提示语	Warning
危险说明	H315 H319 H335
防范说明	P305+P351+P338 P304+P340 P261 P264

产品说明

一般描述

A cell-permeable AG 490 (Cat. No. 658401) tyrphostin analog that acts as an effective STAT3 pathway inhibitor and a much more potent antitumor agent than AG 490 in inhibiting malignant glioma growth both in cultures in vitro (IC₅₀ = 5.6 and 3.7 µM in a viability assay using U87-MG and U373-MG, respectively; no inhibition against nontumor NHA at 10 µM) and in mice in vivo. Shown to cross blood-brain barrier in mice in vivo. Also available in InSolution format (Cat. No. 573129.
A cell-permeable AG 490 (Cat. No. 658401) tyrphostin analog that acts as an effective STAT3 pathway inhibitor and a much more potent antitumor agent than AG 490 in inhibiting malignant glioma growth both in cultures in vitro (IC₅₀ = 5.6 and 3.7 µM in a viability assay using U87-MG and U373-MG, respectively; no inhibition against nontumor NHA at 10 µM) and in mice in vivo. Shown to cross blood-brain barrier in mice in vivo.

包装

10 mg in Glass bottle
Packaged under inert gas

生化/生理作用

Cell permeable: yes
Product does not compete with ATP.
Reversible: no
Primary Target
STAT3 pathway
Target IC₅₀: 5.6 and 3.7 µM in inhibiting malignant glioma growth in a viability assay using U87-MG and U373-MG, respectively

警告

Toxicity: Irritant (B)

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

其他说明

Iwamaru, A., et al. 2007. Oncogene,26, 2435.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

产品性质

安全信息

基本信息

安全信息

图形或危害标志
危险性说明	H302: Harmful if swallowed. H315: Causes skin irritation. H319: Causes serious eye irritation. H335: May cause respiratory irritation.
防范说明	P233: Keep container tightly closed. P260: Do not breathe . P261: Avoid breathing . P264: Wash hands thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P271: Use only outdoors or in a well-ventilated area. P280: Wear . P301 + P312: IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. P302 + P352: IF ON SKIN: Wash with plenty of soap and water. P304: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.. P304 + P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P305 + P351 + P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P312: Call a POISON CENTER or doctor/physician if you feel unwell. P321: Specific treatment (see relevant procedures. on this label). P330: Rinse mouth. P332 + P313: If skin irritation occurs: Get medical advice/ attention. P337 + P313: If eye irritation persists: Get medical advice/attention. P340: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P362: Take off contaminated clothing and wash before reuse. P403: Store in a well-ventilated place. P403 + P233: Store in a well-ventilated place. Keep container tightly closed. P405: Store locked up. P501: Dispose of contents/container to in accordance with local regulation .