| Description |
4μ8C (IRE1 Inhibitor III) is a small-molecule inhibitor of IRE1α.
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| Related Catalog |
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| In Vitro |
When applies to the media of ER stressed cultured cells, 4μ8C inhibits Xbp1 splicing in a concentration-dependent manner. 4μ8C dissociates slowly from IRE1, but ishout of inhibitor leads to rapid recovery of Xbp1 splicing in cells[1].The IRE1 endoribonuclease inhibitor 4μ8c prevents the splicing of the XBP1 mRNA in response to ER stress caused by mutant proinsulin production[2]. The inositol-requiring enzyme 1α (IRE1α) is a serine-threonine kinase that plays crucial roles in activating the unfolded protein response. 4μ8C treatment dramatically inhibits IL-4 production by CD4+ T cells under Th0 conditions because both the IL-4 levels in the culture supernatant and the percentage of IL-4 positive cells are reduced by 4μ8C treatment. In addition, both IL-5 and IL-13 production are significantly reduced upon treatment with 4μ8C[3].
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| In Vivo |
4μ8C reverses the ER stress-dependent loss of several known RIDD targets, with an EC50 of approximately 4 μM, approximating that of inhibition of XBP1 target gene activation[1].
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| Cell Assay |
INS-1 (Insulin 2 C96Y-GFP) cells (clone #4S2) cells are either left untreated or treated with 2 μg/mL doxycycline, 2 μg/mL doxycycline and 5 μM 4μ8C or 5 μM 4μ8C alone. After 48 h 50,000 cells/100 μL of media from each treatment well are seeded into a 96-well plate in duplicates. The CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay MTS is performed. The absorbance at 490 nm is then measured with a plate reader.[2].
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| References |
[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.
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