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AZD-1480

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Chemical Structure| 935666-88-9 同义名 : -
CAS号 : 935666-88-9
货号 : A209618
分子式 : C14H14ClFN8
纯度 : 99%+
分子量 : 348.766
MDL号 : MFCD16038904
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(143.36 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+30% PEG300+water 2 mg/mL clear

PO 0.5% CMC-Na 37 mg/mL suspension

生物活性
靶点

  • JAK2

    JAK2, IC50:0.26 nM
描述 The signal transducer and activator of transcription (STAT) activation by cytokines is mediated through the Janus family kinases (Jak), which include four family members, Jak1, Jak2, Jak3, and Tyk2. JAK2 is a Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. JAK2 mediates essential signaling events in both innate and adaptive immunity. Following ligand-binding to cell surface receptors, JAK2 phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. AZD1480 is a potent ATP competitive inhibitor of JAK2 kinase, with an inhibition constant (Ki) of 0.26nM. The enzyme IC50 of AZD1480 against JAK2, JAK1 and JAK3 were <0.4nM, 1.3nM and 3.9nM, respectively, at Km ATP[3]. In TEL-JAK2 cells, AZD1480 concentration-dependently inhibited the phosphorylation of Stat5 ranging from 0.03μM to 1μM, with an IC50 of 46nM. Little or no inhibition of Stat5 phosphorylation was observed in the TEL-Jak3, TEL-Jak1, or TEL-Tyk2 cells at below 1μM AZD1480[3]. At concentrations ranging from 0.5μM to 3μM, AZD1480 blocked cell proliferation and induces apoptosis of myeloma cell lines[4]. In animal experiments, AZD1480 decreased tumor growth in Renca, Kms.11, TC32, Rh18 or patient derived Glioblastoma xenografts. In different experiments, AZD1480 was orally dosed 50mg/kg once a day or 30mg/kg, twice a day[5].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
4C8 1 µM Function Assay 0-16 h inhibits constitutive STAT-3 and JAK2 activation 22027691
4C8 1/10 µM Growth Inhibition Assay 24/48/72 h inhibits cell proliferation at a concentration of 10 µM 22027691
686LN Growth Inhibition Assay 72 h EC50=2.05 ± 1.33 μM 25810010
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
NCT00910728 Primary Myelofibrosis (PMF) ... 展开 >> Post-Polycythaemia Vera Essential Thrombocythaemia Myelofibrosis 收起 << Phase 1 Completed - United States, New York ... 展开 >> Research Site New York, New York, United States United States, Texas Research Site Houston, Texas, United States France Research Site Villejuif Cedex, France 收起 <<
NCT01112397 Solid Malignancies Phase 1 Terminated(Decision to stop de... 展开 >>velopment of AZD1480) 收起 << - United States, Colorado ... 展开 >> Research Site Aurora, Colorado, United States United States, Michigan Research Site Detroit, Michigan, United States United States, Pennsylvania Research Site Philadelphia, Pennsylvania, United States 收起 <<
NCT00910728 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.87mL

0.57mL

0.29mL

14.34mL

2.87mL

1.43mL

28.67mL

5.73mL

2.87mL
参考文献

[1]16(6):487-97.

[2]25(3):538-50.

[3]Hedvat M, Huszar D, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, Buettner R, Proia D, Kowolik CM, Xin H, Armstrong B, Bebernitz G, Weng S, Wang L, Ye M, McEachern K, Chen H, Morosini D, Bell K, Alimzhanov M, Ioannidis S, McCoon P, Cao ZA, Yu H, Jove R, Zinda M. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 2009 Dec 8;16(6):487-97.