GW4869

SKU: orb1303969

Description

GW4869

Research Area

Metabolism Research

Key Properties

• CAS Number: 6823-69-4
• MW: 577.5
• Purity: 99.66%
• Formula: C₃₀H₃₀Cl₂N₆O₂
• SMILES: Cl.Cl.O=C(Nc1ccc(cc1)C1=NCCN1)\C=C\c1ccc(\C=C\C(=O)Nc2ccc(cc2)C2=NCCN2)cc1
• Target: Phospholipase
• Solubility: DMSO:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  SMase:1 μM
• In Vivo:
  METHODS: To detect in vivo activity, GW4869 (2.5 μg/g) was injected intraperitoneally into C57BL/6 mice, and LPS (25 μg/g) was injected 1 h later. RESULTS: Pretreatment of mice with GW4869 attenuated LPS-triggered production of exosomes and pro-inflammatory cytokines in the blood, thereby reducing myocardial inflammation. METHODS: To assay in vivo activity, GW4869 (200 μL of 0.3 mg/mL, 2-2.5 μg/g) was administered intraperitoneally to 5XFAD mice every two days for six weeks. RESULTS: GW4869 reduced amyloid plaque formation in vivo by blocking exosome secretion.
• In Vitro:
  METHODS: Human breast cancer cells MCF-7 were pretreated with GW4869 (10 μM) for 30 min, then incubated with TNF (3 nM) for 6-24 h. Ceramide levels were detected by E. coli diacylglycerol kinase assay. RESULTS: GW4869 significantly inhibited TNF-induced ceramide accumulation, and GW4869 inhibited N-SMase. METHODS: Macrophage RAW264.7 was pretreated with GW4869 (10-20 μM) for 2 h, and then incubated with LPS (1 μg/mL) for 24 h. AchE activity was measured. RESULTS: After pretreatment of macrophages with 10 μM GW4869, LPS-triggered exocytosis was significantly attenuated in macrophages, and the activity of AChE was reduced by 22%. Treatment with 20 μM GW4869 further enhanced this attenuation.
• Cell Research:
  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 Water are added to 50 μL of GW4869 stock suspension). 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Phospholipase, inhibit, Inhibitor, neutral sphingomyelinase, GW 4869, GW4869, GW-4869, GW554869A, GW69A

Compound Identifiers

PubChem CID

16078967