产品说明书

WP1066

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Chemical Structure| 857064-38-1 同义名 : -
CAS号 : 857064-38-1
货号 : A203794
分子式 : C17H14BrN3O
纯度 : 98%
分子量 : 356.217
MDL号 : MFCD12912450
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(126.33 mM)，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

无水乙醇: 15 mg/mL(42.11 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 3.9 mg/mL clear

PO 0.5% CMC-Na 35 mg/mL suspension

生物活性
靶点

  • JAK2

    JAK2, IC50:2.3 μM
描述 The JAK/STAT3 pathway is activated by various cancer types, including glioma, and blockade of the pathway induces cell death in cancer cells. Thus, the JAK/STAT3 pathway is a target for cancer therapy. WP1066 induces degradation of JAK2 and inhibition of its phosphorylation. WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways[3]. WP1066 is a most potent, small molecule, nonphosphorylated STAT3 inhibitor, that strongly binds to STAT3 protein with KD of 300 nM. The IC50 value in HEL cells is 2.3 μM[4]. In a vitro study, AML (acute myelocytic leukemia) cells obtained from the four patients with AML were cultured using the AML blast colony culture assay with or without WP1066 at concentrations ranging from 0.5 to 3.0 μM. The result showed that WP1066 inhibited the proliferation of AML blast colony-forming cells in a dose-dependent manner[5]. In a vivo study, mice with intracerebral melanoma were treated with WP1066 at a dose of 40 mg/kg for 21 days. The result showed that WP1066 could significantly increase the survival rate of intracerebral melanoma mice[6]. Use WP1066 at different concentrations from 0 to10 µM on SNK6 cells to demonstrate the influence of WP1066 on protein expression of p-STAT3 and downstream molecules. The decrease of protein expression for p-STAT3 in SNK6 cells after a 24-h treatment of WP1066 in a dose-dependent manner which indicated the inhibition of the pro-survival factors downstream of STAT3 pathway may be the potential mechanisms contributing to the antitumor effect of WP1066 in nasal NKTCL(Nasal-type natural killer/T-cell lymphoma) cells[7].
作用机制 WP1066 can strongly bind to STAT3 protein and bind to the enzyme pocket of JAK2.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human 30M cells Cytotoxic assay 8 days Cytotoxicity against human 30M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=1.8 μM 24900612
human 73M cells Cytotoxic assay 8 days Cytotoxicity against human 73M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=2.1 μM 24900612
human MM1 cells Function assay 24-72 h Antitumor activity against human MM1 cells after 24 to 72 hrs by MTT assay, ic50=1.2 μM 22036213
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01904123 Metastatic Malignant Neoplasm ... 展开 >>in the Brain Metastatic Melanoma Recurrent Brain Neoplasm Recurrent Glioblastoma Recurrent Malignant Glioma 收起 << Phase 1 Recruiting July 31, 2021 United States, Texas ... 展开 >> M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Amy B. Heimberger    713-563-8717       Principal Investigator: Amy B. Heimberger 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.81mL

0.56mL

0.28mL

14.04mL

2.81mL

1.40mL

28.07mL

5.61mL

2.81mL
参考文献

[1]Tsurumaki H, Katano H, Sato K, Imai R, Niino S, Hirabayashi Y, Ichikawa S. WP1066, a small molecule inhibitor of the JAK/STAT3 pathway, inhibits ceramide glucosyltransferase activity. Biochem Biophys Res Commun. 2017 Sep 16;491(2):265-270. doi: 10.1016/j.bbrc.2017.07.115. Epub 2017 Jul 21. PMID: 28739255.

[2]Verstovsek S, Manshouri T, Quintás-Cardama A, Harris D, Cortes J, Giles FJ, Kantarjian H, Priebe W, Estrov Z. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res. 2008 Feb 1;14(3):788-96. doi: 10.1158/1078-0432.CCR-07-0524. PMID: 18245540.

[3]Ferrajoli A, Faderl S, Van Q, Koch P, Harris D, Liu Z, Hazan-Halevy I, Wang Y, Kantarjian HM, Priebe W, Estrov Z. WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res. 2007 Dec 1;67(23):11291-9. doi: 10.1158/0008-5472.CAN-07-0593. PMID: 18056455.

[4]Hatiboglu MA, Kong LY, Wei J, Wang Y, McEnery KA, Fuller GN, Qiao W, Davies MA, Priebe W, Heimberger AB. The tumor microenvironment expression of p-STAT3 influences the efficacy of cyclophosphamide with WP1066 in murine melanoma models. Int J Cancer. 2012 Jul 1;131(1):8-17. doi: 10.1002/ijc.26307. Epub 2011 Aug 24. PMID: 21792892; PMCID: PMC3319790.

[5]Geng L, Li X, Zhou X, Fang X, Yuan D, Wang X. WP1066 exhibits antitumor efficacy in nasal‑type natural killer/T-cell lymphoma cells through downregulation of the STAT3 signaling pathway. Oncol Rep. 2016 Nov;36(5):2868-2874. doi: 10.3892/or.2016.5091. Epub 2016 Sep 15. PMID: 27633398.