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GW4869 

Cat. No.: HY-19363 Purity: 96.35%
Handling Instructions

GW4869 is a noncompetitive neutral sphingomyelinase inhibitor with an IC50 of 1 μM.

For research use only. We do not sell to patients.

GW4869 Chemical Structure

GW4869 Chemical Structure

CAS No. : 6823-69-4

Size Price Stock Quantity
2 mg USD 90 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
5 mg USD 130 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 220 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
25 mg USD 460 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 790 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 1300 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

GW4869 is a noncompetitive neutral sphingomyelinase inhibitor with an IC50 of 1 μM.

IC50 & Target

IC50: 1 μM (neutral sphingomyelinase)[1]

In Vitro

GW4869 (10 μM) partially inhibits TNF-induced sphingomyelin (SM) hydrolysis, and 20 μM of the compound is protected completely from the loss of SM. The addition of 10-20 μM GW4869 completely inhibits the initial accumulation of ceramide, whereas this effect is partially lost at later time points (24 h). The action of GW4869 occurs downstream of the drop in glutathione. GW4869 is able, in a dose-dependent manner, to significantly protect from cell death. These protective effects are accompanied by significant inhibition of cytochrome c release from mitochondria and caspase 9 activation, therefore localizing N-SMase activation upstream of mitochondrial dysfunction[1].

In Vivo

Pre-treatment with GW4869 significantly impairs release of both exosomes and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in RAW264.7 macrophages. At 12 h after LPS treatment or CLP surgery, WT mice pretreated with GW4869 displays lower amounts of exosomes and pro-inflammatory cytokines in the serum than control PBS-injected mice. Accordingly, GW4869 treatment diminishes the sepsis-induced cardiac inflammation, attenuates myocardial depression and prolongs survival[2].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.7316 mL 8.6580 mL 17.3160 mL
5 mM 0.3463 mL 1.7316 mL 3.4632 mL
10 mM 0.1732 mL 0.8658 mL 1.7316 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

B. cereu sphosphatidylcholine-PLC is incubated in the presence or absence of 10 μM GW4869 in a reaction mixture containing 100 mM Tris, pH 7.2, 25% glycerol, 20 mM p-nitrophenyl/phosphorylcholine, and production of p-nitrophenol is quantified spectrophotometrically at 410 nm. Protein phosphatase 2A from bovine kidney is incubated in the presence or absence of GW4869 in buffer containing 50 mM Tris, pH 7.4, 1 mM dithiothreitol, 100 μM MnCl2, and 20% glycerol, and phosphatase activity is measured[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

GW4869 is routinely stored at −80 °C as a 1.5 mM stock suspension in Me2SO. Right before use, the suspension is solubilized by the addition of 5% methane sulfonic acid (MSA) (2.5 μl of 5% MSA in sterile double-distilled H2O are added to 50 μL of GW4869 stock suspension)[1]. GW4869 is routinely stored at -30 °C as a 1.5 mM stock suspension in DMSO. Immediately before use, this suspension is solubilized by the addition of 0.25% methane sulfonic acid (2.5 mL of 5% methane sulfonic acid in sterile distilled H2O is added to 47.5 mL of GW4869 stock solution). The suspension is mixed and heated at 37 °C until clear[3].

Cells are treated with GW4869 for 30 min and then TNF is added in 10 μL/well. At the indicated time points, 25 μL of MTT stock solution are added to each well and incubated at 37 °C in 5% CO2 for 3 h. The cell viability is using the MTT assay[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

GW4869 is dissolved in DMSO (0.005%).

Mice: The mice are randomly assigned to four groups: PBS, GW4869, PBS+LPS and GW4869+LPS (n=5 per group). GW4869 is intraperitoneally (i.p.) injected at one dose of 2.5μg/g. Mice in the PBS+LPS group are pre-injected i.p. with PBS 1 h prior to an i.p. injection of LPS (25 μg/g). Mice in the group of GW4869+LPS are pre-injected i.p. with GW4869 (2.5μg/g) for 1 h, followed by an i.p. injection of LPS (25 μg/g, 100μl). Mice receive injections of PBS to a comparable volume (100μl) as controls. The survival rate of the PBS+LPS and GW4869+LPS groups are monitored every 6 h for a 36 h period[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

577.5

Formula

C₃₀H₃₀Cl₂N₆O₂

CAS No.

6823-69-4

SMILES

O=C(NC1=CC=C(C2=NCCN2)C=C1)/C=C/C3=CC=C(/C=C/C(NC4=CC=C(C5=NCCN5)C=C4)=O)C=C3.[H]Cl.[H]Cl

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 0.044 mg/mL (Need ultrasonic and warming)

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
GW4869
Cat. No.:
HY-19363
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