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WHI-P154

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Chemical Structure| 211555-04-3 同义名 : JAK3 Inhibitor II;Janus-Associated Kinase 3 Inhibitor II;Janex1.
CAS号 : 211555-04-3
货号 : A134082
分子式 : C16H14BrN3O3
纯度 : 98%
分子量 : 376.205
MDL号 : MFCD02179366
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(132.91 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 47 mg/mL suspension

生物活性
靶点

  • JAK3

    JAK3, IC50:1.8 μM

  • EGFR/ErbB1

    EGFR, IC50:4 nM
描述 WHI-P154 is a potent inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase with an IC50 value of 4nM. It also has modest activity against Janus kinase 3 (JAK3) with an IC50 value of 1.8μM[3]. WHI-P154 at 1 and 4μM significantly enhanced the cytotoxic effects of mitoxantrone and SN-38 in ABCG2-transfected cells but not in HEK293/pcDNA3.1 cells. Treatment of parental KB-3-1 cells and ABCB1-overexpressing KB-C2 cells with 4μM WHI-P154 resulted in moderate inhibition on ABCB1. The exposure of WHI-P154 (1 and 4μM) and 2.5μM FTC significantly increased the intracellular level of [3H]-mitoxantrone in ABCG2-overexpressing cells. Treatment of ABCG2-482-R2 cells with 4μM WHI-P154 blocked the efflux function of ABCG2[4]. In mice bearing H694R or E1384K tumors, intravenous injection of WHI-P154 (1mg/kg per day) for 5 weeks significantly suppressed tumor growth and decreased phospho-Y1604 ALK expression in xenografted tumors when compared with DMSO-treated controls[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.29mL

2.66mL

1.33mL

26.58mL

5.32mL

2.66mL
参考文献

[1]Changelian PS, Moshinsky D, et al. The specificity of JAK3 kinase inhibitors. Blood. 2008 Feb 15;111(4):2155-7.

[2]Sareila O, Korhonen R, et al. JAK inhibitors AG-490 and WHI-P154 decrease IFN-gamma-induced iNOS expression and NO production in macrophages. Mediators Inflamm. 2006;2006(2):16161.

[3]Changelian PS, Moshinsky D, Kuhn CF, et al. The specificity of JAK3 kinase inhibitors [published correction appears in Blood. 2009 Oct 1;114(14):3132. Dosage error in article text; Whipple, David A [added]]. Blood. 2008;111(4):2155-2157. doi:10.1182/blood-2007-09-115030

[4]Zhang H, Zhang YK, Wang YJ, et al. WHI-P154 enhances the chemotherapeutic effect of anticancer agents in ABCG2-overexpressing cells. Cancer Sci. 2014;105(8):1071-1078. doi:10.1111/cas.12462

[5]Wang YW, Tu PH, Lin KT, Lin SC, Ko JY, Jou YS. Identification of oncogenic point mutations and hyperphosphorylation of anaplastic lymphoma kinase in lung cancer. Neoplasia. 2011;13(8):704-715. doi:10.1593/neo.11222