GW4869

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.

CAS No. 6823-69-4

サイズ	価格(税別)	在庫状況
5mg	JPY 22000	国内在庫あり
25mg	JPY 59500	国内在庫なし(納期7~10日)
100mg	JPY 145500	国内在庫あり
1g	JPY 445500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（62）

質量管理及び製品安全説明書

現在のバッチを見る： 純度：>97%

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GW4869と併用されることが多い化合物

Bortezomib

GW4869 increases cortical bone volume and sensitizes the myeloma cells to bortezomib, leading to a stronger anti-tumor response when used together.

Faict S, et al. Blood cancer journal 8.11 (2018): 105.

Doxorubicin

GW4869 and PEGylated liposomal doxorubicin (PLD) cotreatment significantly increases cytotoxic cell death in U937 cells.

Hekmatirad S, et al. Front Immunol. 2021 Jun 4;12:692654.

Bisindolylmaleimide I (GF109203X)

GW4869 and Bisindolylmaleimide I can significantly restore the expression of miR-16-5p in vitro and lead to malignant pleural mesothelioma (MPM) cell death.

Desage AL, et al. Cancers (Basel). 2021 Jun 26;13(13):3205.

Bevacizumab (anti-VEGF)

GW4869 inhibits production of extracellular vesicles (EVs) and increases the effects of bevacizumab on U87 glioblastoma (GBM) cells viability.

Simon T, et al. Mol Cancer. 2018 Aug 31;17(1):132.

LY294002

GW4869 and LY294002 combination use decreases HIV-1 sequestration in polarized tonsil epithelial cells.

Yasen A, et al. Virology. 2018 Feb;515:92-107.

GW4869関連製品

関連ターゲット	PLA2 PLC PLD LYPLA1 Smase	もっと見る
関連製品	U73122 Varespladib (LY315920) Tanshinone I Darapladib Quinacrine 2HCl Polydatin CAY10593 (VU0155069) m-3M3FBS Melittin Trigonelline	もっと見る
関連化合物ライブラリー	Autophagy Compound Library Apoptosis Compound Library Ferroptosis Compound Library Pyroptosis Compound Library Mitochondria-Targeted Compound Library	もっと見る

シグナル伝達経路

Phospholipase (e.g. PLA)シグナル伝達経路

Phospholipase (e.g. PLA)阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
OPM2	Proliferation assay	0, 1.25, 2.5, 5, 10, 20, 40 μmol/L	24 h	the cell proliferation rate was increased after GW4869 treatment. The inhibition of cell proliferation was only significant when the concentration of GW4869 was 40 μmol/L or higher.	28858294
MCF7	Function assay	10-20 μM		the addition of 10 μM GW4869 significantly inhibited TNF-induced SM hydrolysis, whereas 20 μM of the compound protected completely from the loss of sphingomyelin	12154098
JJN3	Cell viability assay		72 h	cytotoxic to a panel of MM cell lines	28211573
U266	Cell viability assay		72 h	cytotoxic to a panel of MM cell lines	28211573
NCI-H929	Cell viability assay		72 h	cytotoxic to a panel of MM cell lines	28211573
RPMI-8226	Cell viability assay		72 h	cytotoxic to a panel of MM cell lines	28211573
Daudi	Cell viability assay		72 h	not cytotoxic to non-MM cell lines or PBMCs	28211573
Jurkat	Cell viability assay		72 h	not cytotoxic to non-MM cell lines or PBMCs	28211573
K562	Cell viability assay		72 h	not cytotoxic to non-MM cell lines or PBMCs	28211573
PBMCs	Cell viability assay		72 h	not cytotoxic to non-MM cell lines or PBMCs	28211573
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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.

Targets

SMase ^[1]
(Cell-free assay)

1 μM

In Vitro
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].
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Immunofluorescence	Nrf2		29794115

In Vivo
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].
動物実験	動物モデル	Mice with a complete loss of nSMase2 activity (background: C57BL/6J mice)
	投与量	1.25 mg/kg
	投与経路	i.p.

参考
[1] Luberto C, et al. J Biol Chem. 2002, 277(43):41128-39. [2] Tabatadze N, et al. J Neurosci Res. 2010, 88(13):2940-51. [3] Dinkins MB, et al. Neurobiology of Aging. 2014, 35(8):1792-800.

参考

化学情報

分子量	577.5	化学式	C₃₀H₂₈N₆O₂.₂HCl.XH₂O
CAS No.	6823-69-4	SDF	Download GW4869 SDFをダウンロードする
Smiles	C1CN=C(N1)C2=CC=C(C=C2)NC(=O)C=CC3=CC=C(C=C3)C=CC(=O)NC4=CC=C(C=C4)C5=NCCN5.Cl.Cl
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 1 mg/mL ( (1.73 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo Batch: Add solvents to the product individually and in order.					投与溶液組成計算機
	Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.05mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 1 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.	投与溶液組成計算機
Clear solution	5% DMSO 1 95% corn oil	0.05mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 1 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.25mg/ml	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 5 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):