GW4869

製品コードS7609 バッチS760901

印刷

化学情報

Chemical Structure Synonyms GW69A, GW554869A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C30H28N6O2.2HCl.XH2O
分子量 577.5 CAS No. 6823-69-4
Solubility (25°C)* 体外 DMSO 1 mg/mL (1.73 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 GW4869 (GW69A, GW554869A) is a neutral, noncompetitive inhibitor of sphingomyelinase (SMase) with an IC50 of 1 μM. It is selective for N-SMase, and does not inhibit acid SMase at up to at least 150 μM, also is a commonly used exosome inhibitor.
in vitro GW4869 inhibits N-SMase not only in vitro but also in a cellular model. GW4869 does not significantly impair TNF-induced NF-κB translocation to nuclei. Therefore, GW4869 does not interfere with other key TNF-mediated signaling effects. GW4869 is able, in a dose-dependent manner, to significantly protect from cell death as measured by nuclear condensation, caspase activation, PARP degradation, and trypan blue uptake. 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. At up to 150 μM, GW4869 does not inhibit the cloned human A-SMase. GW4869 shows no or minor inhibitory activity versus other hydrolytic enzymes, such as bacterial phosphatidylcholine-PLC and bovine protein phosphatase 2A, and it shows significantly higher activity versus the rat brain enzyme compared with the human lyso-PAF PLC[1].
in vivo Systemic administration of GW4869 does not alter the ceramide or sphingomylein content of liver, heart or skeletal muscle but does decrease the ceramide content and increase the sphingomyelin content in brain. Inhibition of nSMase2 with GW4869 slowed learning. Mice administered GW4869 do not progressively decrease latency to locate the hidden platform with repeated training trials, suggesting that they has difficulty learning to use spatial cues to navigate the pool[2]. Intraperitoneal injection of GW4869 reduces the levels of brain and serum exosomes, brain ceramide, and Aβ1-42 plaque load. GW4869 reduces amyloid plaque formation in vivo by preventing exosome secretion. GW4869 may have a low toxicity at levels needed to achieve a biological effect from nSMase2 inhibition[3].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MCF7 cells
濃度 10-20 μM
反応時間 30 min
実験の流れ

MCF7 human breast cancer cells are routinely cultured in RPMI 1640 containing 10% FBS at 37 °C in 5% CO2. Unless otherwise indicated, for treatment, cells are seeded at 1.7 × 106 cells/10-cm culture dish in 10 ml of complete medium; after 24 h, the medium is replaced with 7 ml of RPMI 1640 containing 2% FBS and 25 mM Hepes, pH 7.5, and the cells are rested for 2 h prior to treatment. 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; therefore, the concentration of the GW4869 stock solution at the time of the experiments is 1.43 mM). The suspension is mixed and warmed up at 37 °C until clear. Cells are preincubated with the inhibitor for 30 min prior to treatment with TNF. Control cells are treated with Me2SO containing 5% MSA, similarly to the samples receiving the GW4869 solution. When different doses of GW4869 are tested, amounts of vehicle solution are added in order to equal the volume of GW4869 used for the highest dose.
動物実験 動物モデル Mice with a complete loss of nSMase2 activity (background: C57BL/6J mice)
投薬量 1.25 mg/kg
投与方法 i.p.

カスタマーフィードバック

Data from [Data independently produced by , , Cancer Lett, 2018, 433:210-220]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and Dual-Targeted Coxsackievirus B3 [ ACS Nano, 2024, 18(5):4241-4255] PubMed: 38278522
Exosomal circRHCG promotes breast cancer metastasis via facilitating M2 polarization through TFEB ubiquitination and degradation [ NPJ Precis Oncol, 2024, 8(1):22] PubMed: 38287113
Alpha-hederin reprograms multi-miRNAs activity and overcome small extracellular vesicles-mediated paclitaxel resistance in NSCLC [ Front Pharmacol, 2024, 15:1257941] PubMed: 38362150
Effects of extracellular vesicles from adipose-derived stem cells on human keloid fibroblasts via the SOCS1/JAK2/STAT3 pathway [ J Cosmet Dermatol, 2024, 10.1111/jocd.16117] PubMed: 38288516
Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer [ Cancer Commun (Lond), 2023, 43(8):909-937] PubMed: 37434399
Manipulation of PD-L1 Endosomal Trafficking Promotes Anticancer Immunity [ Adv Sci (Weinh), 2023, 10(6):e2206411] PubMed: 36567273
Cold exposure protects against medial arterial calcification development via autophagy [ J Nanobiotechnology, 2023, 21(1):226] PubMed: 37461031
M1 macrophage-derived exosomes promote autoimmune liver injury by transferring long noncoding RNA H19 to hepatocytes [ MedComm -2020), 2023, 4(4):e303] PubMed: 37398637
CX3CR1hi macrophages sustain metabolic adaptation by relieving adipose-derived stem cell senescence in visceral adipose tissue [ Cell Rep, 2023, 42(5):112424] PubMed: 37086405
Bone mesenchymal stem cell extracellular vesicles delivered miR let-7-5p alleviate endothelial glycocalyx degradation and leakage via targeting ABL2 [ Cell Commun Signal, 2023, 21(1):205] PubMed: 37587494

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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