412512

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).

• Synonyme(s) : 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
• Formule empirique (notation de Hill): C₁₁H₈O₄
• Numéro CAS: 14003-96-4
• Poids moléculaire : 204.18
• Numéro MDL: MFCD12027255
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.28

Propriétés

• Niveau de qualité: 100
• Pureté: ≥95% (HPLC)
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: yellow
• Solubilité: DMSO: 25 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: 2-8°C
• Chaîne SMILES: O=C(C=C1C)OC2=C1C=CC(O)=C2C=O
• InChI: 1S/C11H8O4/c1-6-4-10(14)15-11-7(6)2-3-9(13)8(11)5-12/h2-5,13H,1H3
• Clé InChI: RTHHSXOVIJWFQP-UHFFFAOYSA-N

Description

Description générale

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.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
IRE1

Reversible: yes

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months.

Autres remarques

Cross, B.C.S., et al. 2012. Proc. Natl. acad. Sci. USA109, E869.

Informations légales

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable