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(E/Z)-BIX02189

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Chemical Structure| 1094614-85-3 同义名 : BIX 02189
CAS号 : 1094614-85-3
货号 : A140614
分子式 : C27H28N4O2
纯度 : 99%+
分子量 : 440.54
MDL号 : MFCD18074528
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

2% DMSO+30% PEG 300+5% Tween 80+water 10 mg/mL

生物活性
靶点

  • MEK5

    MEK5, IC50:1.5 nM
描述 MEK5 is a dual specificity protein kinase that belongs to the mitogen-activated protein kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. BIX-02189 is a selective inhibitor of MEK5 with IC50 value of 1.5nM. BIX-02189 also inhibits ERK5, TGFβR1, ABL1, CSF1R, JAK3, KIT, LCK, MAPK14, RPS6KA3,RPS6KA6 and SRC with IC50 values of 59nM, 580nM, 2400nM, 46nM, 1000nM, 440nM, 1100nM, 250nM, 3700nM, 2100nM, 990nM and 7600nM, respectively. In vitro, BIX-02189 inhibited Hela and HEK293cells with IC50 values of 0.53nM and 0.26nM, respectively[3]. Treatment A549 lung cancer cells with 2.5-10μM BIX-02189 completely hindered the EGF-induced phosphorylation of ERK5 in a concentration-dependent manner without affecting the phosphorylation of ERK1/2. BIX02189 significantly abolished TGF-β1-mediated E-cadherin repression and N-cadherin induction. In addition, BIX02189 inhibited TGF-β1-induced cell motility and activation of MMP-2 in A549 lung cancer cells. In vivo, Intraperitoneal administration of BIX-02189 at 20mg/kg once daily for 3 weeks inhibited TGF-β receptor type I (TβRI) derived lung metastasis in TβRI-derived A549 xenograft mouse model[4].
作用机制 BIX-02189 inhibits catalytic function of MEK5 and blocks phosphorylation of ERK. [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
human HeLa cells Function assay Inhibition of ERK5 phosphorylation in sorbitol-stimulated human HeLa cells, IC50=0.059 μM 23656407
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.27mL

0.45mL

0.23mL

11.35mL

2.27mL

1.13mL

22.70mL

4.54mL

2.27mL
参考文献

[1]Lim JH, Woo CH. Laminar flow activation of ERK5 leads to cytoprotective effect via CHIP-mediated p53 ubiquitination in endothelial cells. Anat Cell Biol. 2011 Dec;44(4):265-73.

[2]Tatake RJ, O'Neill MM, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun. 2008 Dec 5;377(1):120-5.

[3]TTatake RJ, O'Neill MM, Kennedy CA, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun. 2008;377(1):120-125

[4]Park SJ, Choi YS, Lee S, et al. BIX02189 inhibits TGF-β1-induced lung cancer cell metastasis by directly targeting TGF-β type I receptor. Cancer Lett. 2016;381(2):314-322

[5]Tatake RJ, O'Neill MM, Kennedy CA, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun. 2008;377(1):120-125