4μ8CIRE1 Rnase inhibitor, potent and non-toxic CAS# 14003-96-4 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 14003-96-4 | SDF | Download SDF |
| PubChem ID | 12934390 | Appearance | Powder |
| Formula | C11H8O4 | M.Wt | 204.18 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | IRE1 Inhibitor III | ||
| Solubility | DMSO : ≥ 27 mg/mL (132.24 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 7-hydroxy-4-methyl-2-oxochromene-8-carbaldehyde | ||
| SMILES | CC1=CC(=O)OC2=C1C=CC(=C2C=O)O | ||
| Standard InChIKey | RTHHSXOVIJWFQP-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C11H8O4/c1-6-4-10(14)15-11-7(6)2-3-9(13)8(11)5-12/h2-5,13H,1H3 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Selective inhibitor of IRE1α ribonuclease (RNase) activity (IC50 = 60 nM). Blocks substrate access to the active site of IRE1α. Inactivates IRE1α-mediated mRNA degradation. Displays no effect on the IRE1α-related endoribonuclease RNase L. |
4μ8C Dilution Calculator
4μ8C Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 4.8976 mL | 24.4882 mL | 48.9764 mL | 97.9528 mL | 122.441 mL |
| 5 mM | 0.9795 mL | 4.8976 mL | 9.7953 mL | 19.5906 mL | 24.4882 mL |
| 10 mM | 0.4898 mL | 2.4488 mL | 4.8976 mL | 9.7953 mL | 12.2441 mL |
| 50 mM | 0.098 mL | 0.4898 mL | 0.9795 mL | 1.9591 mL | 2.4488 mL |
| 100 mM | 0.049 mL | 0.2449 mL | 0.4898 mL | 0.9795 mL | 1.2244 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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The inositol-requiring enzyme 1α (IRE1α) is a serine-threonine kinase that plays crucial roles in activating the unfolded protein response. Studies suggest that IRE1α is activated during thymic T cell development and in effector CD8+ T cells. 4μ8C is a potent and selective IRE1 Rnase inhibitor.
In vitro: 4μ8c is a potent and non-toxic inhibitor of IRE1 RNase activation in response to both hypoxia and other ER stress-inducing agents. This compound effectively inhibited IRE1 induced activation of the downstream target genes in both HCT116 colorectal cancer and KP4 pancreatic cancer cell lines under hypoxia. However, despite potent inhibition of IRE1 activation and the, 4μ8c had no effect on cell proliferation or clonogenic survival of HCT116 and KP4 cells during exposure to hypoxia or anoxia. Similarly, 4μ8c inhibition of IRE1 did not sensitize cells to other ER stress inducing agents [1].
In vivo: 4μ8C has not been tested in vivo, probably because of its unfavourable pharmacokinetics.
Clinical trial: Up to now, 4μ8C is still in the preclinical development stage.
Reference:
[1] Dan Cojocari, Ravi Vellanki, Brandon Sit, Marianne Koritzinsky, and Bradly G. Wouters. IRE1 and PERK as targets of cellular adaptation and survival to hypoxia. Mol Cancer Ther 2013;12(11 Suppl):C284.
[2] Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat Rev Drug Discov. 2013 Sep;12(9):703-19.
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The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule.[Pubmed:22315414]
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):E869-78.
IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme-inhibitor complex. The inhibitor (abbreviated 4mu8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings.
