GW 4869

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种细胞渗透性、对称的二氢咪唑酰胺化合物，可作为 N-SMase（中性鞘磷脂酶）的有效、特异性、非竞争性抑制剂 [IC50 = ~ 1 μM，大鼠脑；鞘磷脂的 Km ~13 μM]。

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.

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.

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.

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Metabolic Enzyme/Protease

Phospholipase

neutral sphingomyeliN/Ase

Cancer

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6823-69-4

577.5

C30H30Cl2N6O2

>98% (HPLC)

Soluble in DMSO

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

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(-20℃)

With Ice Pack

≥ 2 years