5.30352

CD40-TRAF6 Signaling Inhibitor, 6877002

• 別名: CD40-TRAF6 Signaling Inhibitor, 6877002, 3-((2,5-Dimethylphenyl)amino)-1-phenyl-2-propen-1-one, (2 E)-3-((2,5-Dimethylphenyl)amino)-1-phenyl-2-propen-1-one, 3-((2,5-Dimethylphenyl)amino)-1-phenyl-2-propen-1-one, (2E)-3-((2,5-Dimethylphenyl)amino)-1-phenyl-2-propen-1-one
• 実験式（ヒル表記法）: C₁₇H₁₇NO
• CAS番号: 433249-94-6
• 分子量: 251.32
• UNSPSCコード: 51111800
• PubChem Substance ID: 2735089
• NACRES: NA.77

特性

• アッセイ: ≥95% (NMR)
• 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: yellow
• 溶解性: DMSO: 100 mg/mL
• 保管温度: 2-8°C
• SMILES記法: COC(=O)C1=NC=NN1

詳細

詳細

A cell-permeable propenone compound that disrupts TNF receptor-associated factor 6 (TRAF6) and CD40 coupling by targeting TRAF6 via direct affinity interaction (K_d = 97 µM), effectively inhibiting LPS-induced NF-κB activation in murine macrophage RAW264.7 (IC₅₀ 15.9 µM; drug treatment starts 1 h prior to 2 h CD40 expression induction by LPS) as well as anti-CD40 antibody FGK45-stimulated IL-1β expression (IC₅₀<10 µM; drug treatment starts 1 h prior to 6 h antibody stimulation). Daily intraperitoneal injection in vivo (10 µmol/kg/d = 2.513 mg/kg/d) during the last 6 weeks of a 12-week murine high fat diet-induce obesity (DIO) study is reported to improve insulin sensitivity, reduce hepatosteatosis, and prevent obesity-related inflammation in fat tissue (AT), as evidenced by a 40% less CD11b⁺F4/80⁺CD11c⁺ M1 macrophages in the stromal vascular fraction (SVF) of gonadal AT (gonAT) than the control DIO mice. Genetic studies likewise reveal that disruption of TRAF6-mediated CD40 signaling ameliorates obesity related complications, while CD40 knockout or deficit in TRAF2/3/5-CD40 interaction exacerbates metabolic complications in DIO mice.

A cell-permeable, bioavailable propenone compound that specifically targets TNF receptor-associated factor 6 (TRAF6; K_d = 97 µM for TRAF6 C-domain) and disrupts its functional coupling with CD40. A six-week treatment of C57BL/6 mice fed high fat diet (HFD) with this compound show significant improvement in insulin sensitivity and hepatosteatosis without affecting HFD-induced weight gain. Also reported to reduce gonadal adipose tissue inflammation and diminish the number of CD11b⁺F4/80⁺CD11c⁺ M1 macrophages. Inhibits NF-κB activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (IC₅₀ 15.9 µM) and reduce IL-1β and IL-6 expression in anti-CD40 antibody FGK45-stimulated primary bone marrow-derived macrophages.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
TRAF6

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

Chatzigeorgiou, A., et al. 2014. Proc. Natl. Acad. Sci. USA111, 2686.

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