4μ8C

Names

[ Name ]:
4μ8C

[Synonym ]:
7-Hydroxy-4-methyl-2-oxo-2H-1-benzopyran-8-carboxaldehyde
7-hydroxy-4-methyl-2-oxo-2H-chromen-8-carbaldehyde
7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde
2H-1-Benzopyran-8-carboxaldehyde,7-hydroxy-4-methyl-2-oxo
8-formyl-7-hydroxy-4-methyl-coumarin
8-formyl-4-methyl-7-hydroxycoumarin
8-formyl-7-hydroxy-4-methyl-2H-<1>-benzopyran-2-one
4μ8C
8-Formyl-7-hydroxy-4-methylcoumarin

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> IRE1

Research Areas >> Metabolic Disease

[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].

[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].

[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].

[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.

[Related Small Molecules]

STF-083010 | KIRA6 | APY 29 | MKC3946 | GSK2850163 | MKC9989 | MKC8866 | NSC95682 | B I09

Chemical & Physical Properties

[ Density]:
1.406±0.06 g/cm3 (20 ºC 760 Torr)

[ Melting Point ]:
189-190 ºC (ethanol )

[ Molecular Formula ]:
C₁₁H₈O₄

[ Molecular Weight ]:
204.17900

[ Exact Mass ]:
204.04200

[ PSA ]:
67.51000

[ LogP ]:
1.61950

[ Storage condition ]:
-20℃

[ Water Solubility ]:
Very slightly soluble (0.59 g/L) (25 ºC)

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2932209090

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2932209090

[ Summary ]:
2932209090. other lactones. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

A conformational RNA zipper promotes intron ejection during non-conventional XBP1 mRNA splicing.

EMBO Rep. 16 , 1688-98, (2015)

The kinase/endonuclease IRE1 is the most conserved signal transducer of the unfolded protein response (UPR), an intracellular signaling network that monitors and regulates the protein folding capacity...