567715

N-SMase Inhibitor, GW4869

The N-SMase Inhibitor, GW4869, also referenced under CAS 6823-69-4, controls the biological activity of N-SMase. This small molecule/inhibitor is primarily used for Cell Signaling applications.

• Sinónimos: N-SMase Inhibitor, GW4869, Sphingomyelinase, Neutral, Inhibitor GW4869, GW69A, GW554869A
• Fórmula empírica (notación de Hill): C₃₀H₂₈N₆O₂ · 2HCl
• Número de CAS: 6823-69-4
• Peso molecular: 577.50
• Código UNSPSC: 12352200
• NACRES: NA.77

Propiedades

• Nivel de calidad: 100
• Ensayo: ≥90% (NMR)
• Formulario: solid
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; desiccated (hygroscopic); protect from light
• color: pale yellow
• solubilidad: DMSO: 200 μg/mL
• Condiciones de envío: wet ice
• temp. de almacenamiento: −20°C
• InChI: 1S/C30H28N6O2.2ClH/c37-27(35-25-11-7-23(8-12-25)29-31-17-18-32-29)15-5-21-1-2-22(4-3-21)6-16-28(38)36-26-13-9-24(10-14-26)30-33-19-20-34-30;;/h1-16H,17-20H2,(H,31,32)(H,33,34)(H,35,37)(H,36,38);2*1H/b15-5+,16-6+;;
• Clave InChI: NSFKAZDTKIKLKT-CLEIDKRQSA-N

Descripción

Descripción general

A cell permeable, symmetrical dihydroimidazolo-amide that acts as a potent, specific, and non-competitive inhibitor of neutral sphingomyelinase (N-SMase) (IC₅₀ = 1 µM, rat brain N-SMase). Reported to inhibit tumor necrosis factor α (TNF-α) induced sphingomyelin hydrolysis (100% inhibition at 20 µM) and TNF-α-induced cell death in MCF7 cells. Does not interfere with other TNF-α-mediated signaling events, such as de novo ceramide synthesis and NF-κB activation and nuclear translocation. Exhibits no effect on cellular glutathione levels that are normally reduced in response to TNF-α. Does not inhibit acid sphingomyelinase (A-SMase) or bacterial phosphatidylcholine-specific phospholipase C (PC-PLC). Shown to weakly inhibit bovine protein phosphatase 2_A (PP2_A) and human lyso-PAF PLC, an enzyme that hydrolyzes sphingomyelin in vitro.

A cell-permeable, symmetrical dihydroimidazolo-amide compound that acts as a potent, specific, non-competitive inhibitor of N-SMase (neutral sphingomyelinase) [IC₅₀ = ~ 1 µM, rat brain; K_m for sphingomyelin ~13 µM]. Does not inhibit human A-SMase (acid sphingomyelinase) even at 150 µM. Weakly inhibits the activities of bovine protein phosphatase 2A and mammalian lyso-PAF PLC, while no inhibition is observed for bacterial phosphatidylcholine-specific PLC. Reported to offer complete protection against TNF-α or diamine-induced cell death in MCF7 breast cancer cells at 20 µM. Does not modify the intracellular glutathione levels or interfere with TNF-α or diamine-mediated signaling effects.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
N-Smase rat brain

Product does not compete with ATP.

Reversible: no

Target IC₅₀: 1 µM rat brain N-SMase (neutral sphingomyelinase); Km for sphingomyelin ~13 µM

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

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

Otras notas

Marchesini, N., et al. 2003. J. Biol. Chem. In press.
Luberto, C., et al. 2002. J. Biol. Chem.277, 41128
Okamoto, Y., et al. 2002. FEBS Lett.530, 140.

Información legal

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

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable