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.

• Synonym(s): N-SMase Inhibitor, GW4869, Sphingomyelinase, Neutral, Inhibitor GW4869, GW69A, GW554869A
• Empirical Formula (Hill Notation): C₃₀H₂₈N₆O₂ · 2HCl
• CAS Number: 6823-69-4
• Molecular Weight: 577.50
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Quality Level: 100
• assay: ≥90% (NMR)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; desiccated (hygroscopic); protect from light
• color: pale yellow
• solubility: DMSO: 200 μg/mL
• shipped in: wet ice
• storage temp.: −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+;;
• InChI key: NSFKAZDTKIKLKT-CLEIDKRQSA-N

Description

General description

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.

Biochem/physiol Actions

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

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

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.

Legal Information

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

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable