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AZ3146

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Chemical Structure| 1124329-14-1 同义名 : -
CAS号 : 1124329-14-1
货号 : A174095
分子式 : C24H32N6O3
纯度 : 98+%
分子量 : 452.549
MDL号 : MFCD18384959
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(232.02 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：
生物活性
靶点

  • Kinesin

    Mps1, IC50:~35 nM
描述 Monopolar spindle 1 (Mps1) is a spindle assembly checkpoint kinase that plays an essential role in the regulation of mitosis. AZ3146 inhibits human Mps1 with an IC50 value of 35 nM. In nocodazole-arrested Hela cells, AZ3146 at 1 – 30 μM inhibited the autophosphorylation of full-length Mps1. AZ3146 at 2 µM reduced the time for Hela cells to complete mitosis from 90 min to 32 min. Nearly 90% of AZ3146-treated Hela cells underwent abnormal mitoses with around 50% entering anaphase without aligning all the chromosomes and almost 30% exiting mitosis without chromosome segregation. AZ3146 at 2 µM also decreased the levels of Mad1 and Mad2 to 60% and 15%, respectively. The kinetochore recruitment of O-Mad2 in Hela cells was also blocked by at 2 µM AZ3146[3]. The exposure of GSK923295, an inhibitor targeting the mitotic kinesin Cenp-E, combined with 2 µM AZ3146 induced whole chromosome aneuploidies in cells without causing DNA damage and significant disruption to the spindle[4]. In AZ3146-resistent HCT116 cells created by long-term exposure of AZ3146, 24-hour incubation of 1 and 2 µM AZ3146 abolished the G1 and G2 - M peaks in the parental cell line and made them rapidly exit from mitosis[5].
作用机制 AZ3146 might inhibit Mps1 by promoting its kinetochore localization[3].
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 HCT116 cells Function assay Inhibition of Myc-tagged wild type MPS1 autophosphorylation in human HCT116 cells after 2 hrs in presence of proteosome inhibitor MG132, IC50=0.72 μM 24256217
human HCT116 cells Growth inhibition assay 72 h Growth inhibition in human HCT116 cells after 72 hrs by MTT assay, GI50=1.2 μM 24256217
sf9 insect cells Function assay Inhibition of N-terminal 6XHis-tagged/GST-tagged full length human MPS1 expressed in recombinant baculovirus infected sf9 insect cells using 5FAM-DHTGFLTEYVATRCONH2 as substrate after 60 to 90 mins by fluorescence assay, IC50=7 nM 24256217
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.21mL

0.44mL

0.22mL

11.05mL

2.21mL

1.10mL

22.10mL

4.42mL

2.21mL
参考文献

[1]Liu X, Liao W, et al. TTK activates Akt and promotes proliferation and migration of hepatocellular carcinoma cells. Oncotarget. 2015 Oct 27;6(33):34309-20.

[2]Hewitt L, Tighe A, et al. Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex. J Cell Biol. 2010 Jul 12;190(1):25-34.

[3]Hewitt L, Tighe A, Santaguida S, White AM, Jones CD, Musacchio A, Green S, Taylor SS. Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex. J Cell Biol. 2010 Jul 12;190(1):25-34.

[4]Bennett A, Bechi B, Tighe A, Thompson S, Procter DJ, Taylor SS. Cenp-E inhibitor GSK923295: Novel synthetic route and use as a tool to generate aneuploidy. Oncotarget. 2015 Aug 28;6(25):20921-32.

[5]Gurden MD, Westwood IM, Faisal A, Naud S, Cheung KM, McAndrew C, Wood A, Schmitt J, Boxall K, Mak G, Workman P, Burke R, Hoelder S, Blagg J, Van Montfort RL, Linardopoulos S. Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. Cancer Res. 2015 Aug 15;75(16):3340-54.