412512
4μ8C
≥95% (HPLC), selective inhibitor of IRE1α, powder
別名:
IRE1 Inhibitor III, 4μ8C, 8-Formyl-7-hydroxy-4-methylcoumarin, 7-Hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde, ER-to-Nucleus Signaling 1 Inhibitor III, Inositol-Reguiring Protein 1 Inhibitor III
製品名
IRE1 Inhibitor III, 4μ8C, IRE1 Inhibitor III, CAS 14003-96-4, is a cell-permeable. Covalent inhibitor of IRE1 RNase activity (IC50 = 550 and 45 nM, respectively, with 0 & 16 min preincubation in RNA cleavage assays).
SMILES string
O=C(C=C1C)OC2=C1C=CC(O)=C2C=O
InChI key
RTHHSXOVIJWFQP-UHFFFAOYSA-N
InChI
1S/C11H8O4/c1-6-4-10(14)15-11-7(6)2-3-9(13)8(11)5-12/h2-5,13H,1H3
assay
≥95% (HPLC)
form
powder
manufacturer/tradename
Calbiochem®
storage condition
OK to freeze
protect from light
color
yellow
solubility
DMSO: 25 mg/mL
shipped in
ambient
storage temp.
2-8°C
Quality Level
Biochem/physiol Actions
Cell permeable: yes
Primary Target
IRE1
IRE1
Reversible: yes
Disclaimer
Toxicity: Standard Handling (A)
General description
A cell-permeable coumarin o-hydroxyaldehyde compound that inhibits IRE1 RNase activity in a time- and dose-dependent manner (IC50 = 550, 230, 180, 100, and 45 nM, respectively, with 0, 2, 4, 8, 16, min drug preincubation in FRET-based RNA cleavage assays) by covalently targeting IRE1 Lys907 via Schiff base formation, effectively preventing ER stress-induced site-specific mRNA splicing as well as RIDD (Regulated IRE1-Dependent Degradation) mRNA degradation (IC50 = 6.9 and 4.1 µM, respectively, against Xbp1 splicing and Scara3 degradation) in MEF cultures following Tunicamycin (Cat. No. 654380) treatment. Also demonstrated to inhibit ER capacity expansion (Effective conc. 32 µM) and amylase secretion (IC50<2 µM) upon stress induction by Dexamethasone (Cat. No. 265005) treatment in rat AR42J tumoral acinar pancreatic cells. Structural analysis reveals that the reduced water accessibility to Lys907 in IRE1 native conformation accounts for the unusual stability of Lys907 Schiff base formation and forms the basis of selective IRE1 RNase inhibition by 4μ8C and STF083010 (Cat. No. 412510). Although 4μ8C, but not STF083010, is also shown to inhibit IRE1 autophosphorylation by Schiff base formation with IRE1 Lys599 in the absence of ADP, cellular nucleotide prevents 4μ8C from targeting IRE1 Lys599 and inhibiting IRE1 kinase activity intracellularly.
A cell-permeable coumarin o-hydroxyaldehyde that inhibits IRE1 RNase activity in a time- and dose-dependent manner (IC50 = 550 and 45 nM, respectively, with 0 and 16 min drug preincubation in RNA cleavage assays) by covalently targeting IRE1 Lys907 via Schiff base formation, effectively preventing ER stress-induced site-specific mRNA splicing as well as RIDD (Regulated IRE1-Dependent Degradation) mRNA degradation (IC50 = 6.9 and 4.1 µM, respectively, against Xbp1 splicing and Scara3 degradation) in MEF cultures following Tunicamycin (Cat. No. 654380) treatment. Comparing to STF083010 (Cat. No. 412510), 4μ8C is also shown to inhibit IRE1 autophosphorylation in cell-free assays via Schiff base formation with IRE1 Lys599 in the absence of ADP, however cellular nucleotide prevents 4μ8C from targeting IRE1 Lys599 intracellularly.
Other Notes
Cross, B.C.S., et al. 2012. Proc. Natl. acad. Sci. USA109, E869.
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
保管分類
11 - Combustible Solids
wgk
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
試験成績書（COA）
製品のロット番号・バッチ番号を入力して、試験成績書（COA） を検索できます。ロット番号・バッチ番号は、製品ラベルに「Lot」または「Batch」に続いて記載されています。
HIF1I?-dependent hypoxia response in myeloid cells requires IRE1I?.
Mawambo, et al.
Journal of Neuroinflammation, 20, 145-145 (2023)
José P Guirao-Abad et al.
mSphere, 5(5) (2020-10-23)
The unfolded protein response (UPR) is a signaling network that maintains homeostasis of the endoplasmic reticulum (ER). In the human-pathogenic fungus Aspergillus fumigatus, the UPR is initiated by activation of an endoribonuclease (RNase) domain in the ER transmembrane stress sensor
Mariana Marques et al.
iScience, 27(3), 109100-109100 (2024-02-26)
Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells' proteostasis throughout the entire infectious
Rohit B Sharma et al.
The Journal of biological chemistry, 295(41), 14164-14177 (2020-08-14)
Success or failure of pancreatic beta cell adaptation to ER stress is a determinant of diabetes susceptibility. The ATF6 and IRE1/XBP1 pathways are separate ER stress-response effectors important to beta cell health and function. ATF6α. and XBP1 direct overlapping transcriptional
Stefanie Marek-Iannucci et al.
JCI insight, 7(6) (2022-02-16)
Kawasaki disease (KD) is the leading cause of noncongenital heart disease in children. Studies in mice and humans propound the NLRP3/IL-1β pathway as the principal driver of KD pathophysiology. Endoplasmic reticulum (ER) stress can activate the NLRP3 inflammasome, but the
グローバルトレードアイテム番号
| カタログ番号 | GTIN |
|---|---|
| 412512-25MGCN | 04055977188189 |
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