[CAS NO. 14003-96-4] 4μ8C
PRODUCTS SPECIFICATIONS [14003-96-4]
DESCRIPTION [14003-96-4]
Overview
| MDL | MFCD12027255 |
|---|---|
| Molecular Weight | 204.18 |
| Molecular Formula | C11H8O4 |
| SMILES | O=CC1=C(O)C=CC2=C1OC(C=C2C)=O |
25 Publications Citing Use of MCE
- [1]Nat Metab. 2022 Sep;4(9):1166-1184.
- [2]J Exp Med. 2022 Apr 4;219(4):e20211498.
- [3]Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):e2110476118.
- [4]ACS Appl Mater Interfaces. 2022 Jun 1;14(21):24144-24159.
- [5]Acta Pharm Sin B. 5 January 2022.
- [6]NPJ Breast Cancer. 2022 Jan 10;8(1):2.
- [7]J Pathol. 2020 Jun;251(2):123-134.
- [8]Oxid Med Cell Longev. 2021 Jan 4;2021:8836818.
- [9]FASEB J. 2022 Jul;36(7):e22401.
- [10]Genes Dis. 2022.
- [11]Food Chem Toxicol. 2021 Jan;147:111911.
- [12]ACS Infect Dis. 2020 Jul 10;6(7):1745-1758.
- [13]Phytomedicine. 2021 Jan;80:153399.
- [14]Acs Biomater Sci Eng. 2020 Mar 9;6(3):1727-1734.
- [15]Front Cell Neurosci. 2021 Mar 25;15:614556.
- [16]Viruses. 2020 Sep 2;12(9):974.
- [17]Toxins. 2020 Jan 16;12(1):55.
- [18]Cell Mol Biol Lett. 2022 Dec 16;27(1):110.
- [19]Infect Immun. 2022 May 19;90(5):e0007922.
- [20]Vet Microbiol. 2020 May;244:108648.
- [21]Biochem Biophys Res Commun. 2020 Jun 30;527(3):805-810.
- [22]ACS Omega. 2021 Jun 8;6(24):15708-15715.
- [23]Toxicon. 2021 Jul 31;S0041-0101(21)00211-7.
- [24]Theriogenology. 2022 May 16;187:205-214.
- [25]Exp Hematol Oncol. 2022 Mar 31;11(1):18.
Summary
4μ8C (IRE1 Inhibitor III) is a small-molecule inhibitor of IRE1α .
In Vitro
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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 EC
50
of approximately 4 μM, approximating that of inhibition of XBP1 target gene activation
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | ApoE -/- mice [4] |
| Dosage: | 10 mg/kg |
| Administration: | I.p. injection; daily; for 4 more weeks |
| Result: | Led to a significant reduction (45.2%) in atherosclerotic lesion area in en face aorta preparations. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 27 mg/mL ( 132.24 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 4.8976 mL | 24.4882 mL | 48.9764 mL |
| 5 mM | 0.9795 mL | 4.8976 mL | 9.7953 mL |
| 10 mM | 0.4898 mL | 2.4488 mL | 4.8976 mL |
-
1.
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.
- [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.