产品说明书

4μ8C

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Chemical Structure| 14003-96-4 同义名 : IRE1 Inhibitor III
CAS号 : 14003-96-4
货号 : A460722
分子式 : C11H8O4
纯度 : 99%+
分子量 : 204.179
MDL号 : MFCD12027255
存储条件：

粉末 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: 25 mg/mL(122.44 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
动物实验配方：

5%DMSO+40%PEG300+5%Tween80+50%water 0.5 mg/mL

生物活性
描述 4μ8C (IRE1 Inhibitor III) is a small-molecule inhibitor of IRE1α[1]. Additionally impedes Xbp1 mRNA splicing in a dose-responsive manner when added to the culture media of ER-stressed cells. This inhibitor's binding to IRE1 is characterized by a slow dissociation rate, although removal of the inhibitor allows for a quick resumption of Xbp1 splicing in the cells[1]. The mechanism by which 4μ8C operates, especially in preventing the splicing of XBP1 mRNA under ER stress conditions, such as those induced by mutant proinsulin production, provides insight into its potential application in managing ER stress-related cellular dysfunctions[2]. Treatment with 4μ8C significantly reduces IL-4 production by CD4+ T cells under Th0 conditions, as evidenced by decreased IL-4 levels in culture supernatants and a lower percentage of IL-4 positive cells. The production of IL-5 and IL-13 is also notably diminished following 4μ8C administration[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 Jeko cells Function assay 24 h Inhibition of XBP-1s expression in human Jeko cells after 24 hrs by immunoblotting analysis, IC50=1.57 μM 24749861
human Mino cells Function assay 24 h Inhibition of XBP-1s expression in human Mino cells after 24 hrs by immunoblotting analysis, IC50=1.62 μM 24749861
SF21 cells Function assay 30 mins Inhibition of human recombinant puritin-His-tagged IRE-1 RNase expressed in SF21 cells using XBP-1 RNA stem loop as substrate incubated for 30 mins prior to substrate addition measured after 2 hrs by FRET-suppression assay, IC50=0.206 μM 24749861
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.90mL

0.98mL

0.49mL

24.49mL

4.90mL

2.45mL

48.98mL

9.80mL

4.90mL
参考文献

[1]Cross BC, et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):E869-78.

[2]Zhang L, et al. IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis. BMC Cell Biol. 2014 Jul 10;15:29.

[3]Kemp K, et al. The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells. J Biol Chem. 2013 Nov 15;288(46):33272-82.

[4]Tufanli O, et al. Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):E1395-E1404.

[5]Nam ST, et al. Suppression of IgE-mediated mast cell activation and mouse anaphylaxis via inhibition of Sykactivation by 8-formyl-7-hydroxy-4-methylcoumarin, 4μ8C. Toxicol Appl Pharmacol. 2017 Oct 1;332:25-31.