GW 4869

SKU: orb1224257

Description

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; Km 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 Y cells at 20 μM. Does not modify the intracellular glutathione levels or interfere with TNF-α or diamine-mediated signaling effects.

Images & Validation

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Key Properties

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CAS Number	6823-69-4
MW	577.5
Purity	>98% (HPLC)
Formula	C₃₀H₃₀Cl₂N₆O₂
SMILES	C1NC(=NC1)C2=CC=C(C=C2)NC(=O)/C=C/C3=CC=C(C=C3)/C=C/C(=O)NC4=CC=C(C=C4)C5=NCCN5.Cl.Cl
Target	Phospholipase
Solubility	Soluble in DMSO

Bioactivity

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In Vivo

Animal model: 10-12 weeks old Male wild-type C57BL/6 mice (Endotoxin-Challenged Mice). Dosage: 2.5 μg/g. Administration: i.p. once (1 h later, followed by an i.p. injection of LPS (2.5 μg/g, 100 μL)). Result: Significantly decreased exosome levels by 37% in sera, compared to levels collected from control mice. At 12 h after LPS injection, the levels of circulating exosomes were increased significantly compared to PBS-controls, as evidenced by a 1.7-fold elevation in the AChE activity. Animal model: 10-12 weeks old Male wild-type C57BL/6 mice (CLP Polymicrobial Sepsis Model). Dosage: 2.5 μg/g. Administration: i.p. once (before sham or CLP surgery). Result: Decreased exosome concentration by 33% compared to mice injected with PBS in sham-surgery controls. CLP-stimulated exosome release was significantly inhibited by pre-treatment of CLP mice compared to CLP mice pre-treated with PBS.

In Vitro

Cell Viability Assay Cell line: MCF7 human breast cancer cells. Concentration: 10-20 μM. Incubation time: 30 min (then treated with TNF (3 nM) followed). Result: Significantly inhibited TNF-induced SM hydrolysis, whereas 20 μM of the compound protected completely from the loss of SM. Cell Viability Assay Cell line: Fresh RAW264.7 macrophages. Concentration: 10 or 20 μM. Incubation time: 2 hours (then treated with 1 μg/mL LPS incubation). Result: LPS-triggered exosome generation was remarkably attenuated in macrophages upon pre-treatment of macrophages with 10 μM GW4869, as evidenced by a 22% reduction in the activity of AChE. Such attenuation was further enhanced by treatment with the dose of 20 μM.

Storage & Handling

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Storage	Storage temperature: -20°C. Stability: ≥ 2 years
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

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Phospholipase

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GW 4869 (orb1224257)

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Purity:	99.66% (May vary between batches)
CAS Number:	6823-69-4
MW:	577.5
Formula:	C₃₀H₃₀Cl₂N₆O₂

GW 4869

Description

Images & Validation

Key Properties

Bioactivity

Storage & Handling

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