4μ8C  (Synonyms: IRE1 Inhibitor III)

4μ8C (IRE1 Inhibitor III) is a small-molecule inhibitor of IRE1α.

When applies to the media of ER stressed cultured cells, 4μ8C (IRE1 Inhibitor III) 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

4μ8c (IRE1 Inhibitor III) (i.p. injection; 10 mg/kg/day for 4 more weeks) leads to a significant reduction (45.2%) in atherosclerotic lesion area in en face aorta preparations. 4μ8c can effectively mitigate plaque development in mice^[4].
? 4μ8C (orally; 10, 50, or 100 mg/kg) suppresses passive cutaneous anaphylaxis (PCA) in mice (ED50 = 25.1 mg/kg)^[5].
? 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

204.18

Solid

C₁₁H₈O₄

14003-96-4

O=CC1=C(O)C=CC2=C1OC(C=C2C)=O

Room temperature in continental US; may vary elsewhere.

• [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]