5.30352

CD40-TRAF6 Signaling Inhibitor, 6877002

• Sinônimo(s): 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
• Fórmula empírica (Notação de Hill): C₁₇H₁₇NO
• Número CAS: 433249-94-6
• Peso molecular: 251.32
• Número MDL: MFCD00205277
• Código UNSPSC: 51111800
• ID de substância PubChem: 2735089
• NACRES: NA.77

Propriedades

• Ensaio: ≥95% (NMR)
• Nível de qualidade: 100
• Formulário: powder
• fabricante/nome comercial: Calbiochem^®
• condição de armazenamento: OK to freeze; protect from light
• cor: yellow
• solubilidade: DMSO: 100 mg/mL
• temperatura de armazenamento: 2-8°C
• cadeia de caracteres SMILES: COC(=O)C1=NC=NN1
• InChI: 1S/C4H5N3O2/c1-9-4(8)3-5-2-6-7-3/h2H,1H3,(H,5,6,7)
• chave InChI: QMPFMODFBNEYJH-UHFFFAOYSA-N

Descrição

Descrição geral

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.

Ações bioquímicas/fisiológicas

Cell permeable: yes

Primary Target
TRAF6

Embalagem

Packaged under inert gas

Advertência

Toxicity: Standard Handling (A)

Reconstituição

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.

Outras notas

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

Informações legais

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

Informações de segurança

• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable