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412512 IRE1 Inhibitor III, 4μ8C - CAS 14003-96-4 - Calbiochem

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).

MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.

Synonyms: 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

Primary Target: IRE1
412512
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Overview

Replacement Information

Key Spec Table

CAS #Empirical Formula
14003-96-4C₁₁H₈O₄

Products

Catalogue NumberPackaging Qty/Pack
412512-25MGCN Glass bottle 25 mg
Description
OverviewA 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.
Catalogue Number412512
Brand Family Calbiochem®
Synonyms8-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
References
ReferencesCross, B.C.S., et al. 2012. Proc. Natl. acad. Sci. USA 109, E869.
Product Information
CAS number14003-96-4
FormYellow powder
Hill FormulaC₁₁H₈O₄
ReversibleY
Structure formula ImageStructure formula Image
Quality LevelMQ100
Applications
Biological Information
Primary TargetIRE1
Purity≥95% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage +2°C to +8°C
Protect from Light Protect from light
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications
Global Trade Item Number
Catalogue Number GTIN
412512-25MGCN 04055977188189

Documentation

IRE1 Inhibitor III, 4μ8C - CAS 14003-96-4 - Calbiochem SDS

Title

Safety Data Sheet (SDS) 

IRE1 Inhibitor III, 4μ8C - CAS 14003-96-4 - Calbiochem Certificates of Analysis

TitleLot Number
412512

References

Reference overview
Cross, B.C.S., et al. 2012. Proc. Natl. acad. Sci. USA 109, E869.
Data Sheet

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision11-October-2012 JSW
Synonyms8-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
DescriptionA 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.
FormYellow powder
Intert gas (Yes/No) Packaged under inert gas
CAS number14003-96-4
Structure formulaStructure formula
Purity≥95% by HPLC
SolubilityDMSO (25 mg/ml)
Storage Protect from light
+2°C to +8°C
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months.
Toxicity Standard Handling
ReferencesCross, B.C.S., et al. 2012. Proc. Natl. acad. Sci. USA 109, E869.