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567715

N-SMase Inhibitor, GW4869

Name: N-SMase Inhibitor, GW4869
Brand: MM

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

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About This Item

Empirical Formula (Hill Notation):

C₃₀H₂₈N₆O₂ · 2HCl

CAS Number:

6823-69-4

Molecular Weight:

577.50

UNSPSC Code:

12352200

NACRES:

NA.77

Assay:

≥90% (NMR)

Form:

solid

Storage condition:

OK to freeze, desiccated (hygroscopic), protect from light

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Properties

Quality Segment

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

Preparation Note

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

Disclaimer

Toxicity: Standard Handling (A)

Storage Class

11 - Combustible Solids

wgk

WGK 3

flash_point_f

Not applicable

flash_point_c