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GW4869

CAS号

6823-69-4

分子式

C30H30Cl2N6O2

主要靶点

Phospholipase

仅限科研使用

Cat No : CM01341

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Synonyms

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

验证数据展示

  • CAS No.: 6823-69-4

    GW4869
    CAS#: 6823-69-4

产品信息

CAS号 6823-69-4
分子式 C30H30Cl2N6O2
主要靶点 Phospholipase
主要通路 代谢
分子量 577.5
纯度 99.66%， 此纯度可做参考，具体纯度与批次有关系，可咨询客服
储存条件 Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
别名 GW69A|GW 4869|GW554869A|GW4869|GW-4869|inhibit|Inhibitor|neutral sphingomyelinase|Phospholipase

靶点活性

SMase:1 μM

体内活性

方法：为检测体内活性，将 GW4869 (2.5 μg/g) 腹腔注射给 C57BL/6 小鼠，1 h 后注射 LPS (25 μg/g)。 结果：GW4869 预处理小鼠可以减弱 LPS 触发的血液中外泌体和促炎细胞因子的产生，从而减少心肌炎症。[2] 方法：为检测体内活性，将 GW4869 (200 μL 0.3 mg/mL，2-2.5 μg/g) 腹腔注射给 5XFAD 小鼠，每两天一次，持续六周。 结果：GW4869 通过阻止外泌体分泌来减少体内淀粉样斑块的形成。[3]

体外活性

方法：人乳腺癌细胞 MCF-7 用 GW4869 (10 μM) 预处理 30 min，再加入 TNF (3 nM) 孵育 6-24 h，使用 E. coli diacylglycerol kinase assay 检测神经酰胺水平。 结果：GW4869 显著抑制了 TNF 诱导的神经酰胺积累。GW4869 对 N-SMase 有抑制作用。[1] 方法：巨噬细胞 RAW264.7 用 GW4869 (10-20 μM) 预处理 2 h，随后用 LPS (1μg/mL) 孵育 24 h，检测 AchE 活性。 结果：用 10μM GW4869 预处理巨噬细胞后，LPS 触发的外泌体生成在巨噬细胞中显著减弱，AChE的 活性降低了 22%。用 20μM GW4869 处理进一步增强了这种衰减。[2]

溶解度

DMSO:< 1 mg/ml

细胞实验

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[1].

参考文献

1.Luberto C, et al. Inhibition of tumor necrosis factor-induced cell death in MCF7 by a novel inhibitor of neutral sphingomyelinase. J Biol Chem. 2002 Oct 25;277(43):41128-39.
2.Essandoh K, et al. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochim Biophys Acta. 2015 Nov;1852(11):2362-71.
3.Dinkins MB, et al. Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging. 2014 Aug;35(8):1792-800.
4.. Heat injured stromal cells‐derived exosomal EGFR enhances prostatic wound healing after thulium laser resection through EMT and NF‐κB signaling. The Prostate. 2019 May 24.
5.Ge M, Qiao Z, Kong Y, et al. Exosomes mediate intercellular transfer of non-autonomous tolerance to proteasome inhibitors in mixed-lineage leukemia[J]. Cancer Science. 2020.
6.Ge M, Qiao Z, Kong Y, et al. Exosomes mediate intercellular transfer of non–autonomous tolerance to proteasome inhibitors in mixed‐lineage leukemia[J]. Cancer Science. 2020, 111(4): 1279.
7.Wang X, Chen Q Z, Zan Y X, et al.?. Exosomal miR‐145‐5p derived from orthohantavirus‐infected endothelial cells inhibits HTNV infection. The FASEB Journal. 2020, 34(10): 13809-13825.

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