5.30588

IκB Ubiquitination Inhibitor, GS143

• 別名: IκB Ubiquitination Inhibitor, GS143, 4-(3-Benzyl-4-(5-(2-fluoro-phenyl)-furan-2-ylmethylene)-5-oxo-4,5-dihydropyrazol-1-yl)-benzoic acid, 4-(3-Benzyl-4-((5-(2-fluorophenyl)furan-2-yl)methylene)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid, GS 143
• 実験式（ヒル表記法）: C₂₈H₁₉FN₂O₄
• CAS番号: 916232-21-8
• 分子量: 466.46
• UNSPSCコード: 51111800
• PubChem Substance ID: 121513876
• NACRES: NA.77

特性

• アッセイ: ≥97% (HPLC)
• 品質水準: 100
• 形状: powder
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: dark red
• 溶解性: DMSO: 25 mg/mL
• 保管温度: 2-8°C
• SMILES記法: C1=CC=C(C=C1)CC2=NN(C(=O)C2=CC3=CC=C(O3)C4=CC=CC=C4F)C5=CC=C(C=C5)C(=O)O

詳細

詳細

A cell-permeable trisubstituted oxo-dihydropyrazolyl-benzoic acid that selectively inhibits the E3 ligase complex SCF^βTrCP1-mediated ubiquitination of phosphorylated IκBα (IC₅₀ = 5.2 µM), displaying little inhibitory potency against IKKβ-catalyzed IκBα phosphorylation, MDM2-mediated p53 ubiquitination, or the protease activities of cathepsin B, chymotrypsin, 20S & 26S proteasome (IC₅₀ >100 µM). Cellular IκBα degradation blockage by GS143 treatment (complete inhibition against TNFα-induced degradation with 30 min 20 µM drug pretreatment in in HeLa S3 and HT29 cultures) effectively inhibits TNFα- and LPS-stimulated NF-κB transcription in HEK293, HT-29, and THP-1 cultures (IC₅₀ from 2.1 to 10.5 µM). Intranasal administration (32 µg/20 µL/mouse) among OVA-sensitized mice 2 h prior to OVA challenge via inhalation greatly suppress OVA challenge-induced NF-κB activation in lung tissue (>90% inhibition of nuclear NF-κB p65 DNA-binding activity 2 h post challenge) and airway inflammation (>80% reduction in eosinophils & lymphocytes in BALF 48 h post challenge) in vivo. GS143 most likely prevents SCF^βTrCP1 from interacting with phosphorylated IκBα without inhibiting SCF^βTrCP1 E3 ligase activity directly, as no apparent accumulation of another known SCF^βTrCP1 substrate β-catenin is seen in HeLa S3 cells upon GS143 treatment (up to 20 µM for 3 h).

A cell-permeable trisubstituted oxo-dihydropyrazolyl-benzoic acid that selectively inhibits the E3 ligase complex SCF^βTrCP1-mediated ubiquitination of phosphorylated IκBα (IC₅₀ = 5.2 µM), displaying little inhibitory potency against IKKβ-catalyzed IκBα phosphorylation, MDM2-mediated p53 ubiquitination, or the protease activities of cathepsin B, chymotrypsin, 20S & 26S proteasome (IC₅₀ >100 µM). Effectively inhibits TNFα- and LPS-stimulated NF-κB transcription in HEK293, HT-29, and THP-1 cultures (IC₅₀ from 2.1 to 10.5 µM). Intranasal administration (32 µg/20 µL/mouse) among OVA-sensitized mice 2 h prior to OVA challenge via inhalation greatly suppress NF-κB activation in lung tissue and airway inflammation in vivo. GS143 most likely prevents SCF^βTrCP1 from interacting with phosphorylated IκBα without inhibiting SCF^βTrCP1 E3 ligase activity directly.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
phosphorylated IκBα

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Use only fresh DMSO for reconstitution.

その他情報

Hirose, K., et al. 2008. Biochem. Biophys. Res. Commun.374, 507.

Nakajima, H., et al. 2008. Biochem. Biophys. Res. Commun.368, 1007.

法的情報

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

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable