GW4869-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEGW4869Cat.No.:HY-19363CASNo.:6823-69-4分?式:C??H??Cl?N?O?分?量:577.5作?靶點:Phospholipase作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體DMSO:<1mg/mL(insolubleorslightlysoluble)外H2O:<0.1mg/mL(insoluble)實請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制驗儲備液，并請注意儲備液的保存?式和期限。BIOLOGICALACTIVITY?物活性GW4869?競爭性的中性鞘磷脂酶(N-SMase)抑制劑，IC50值為1μM。GW4869外泌體合成/釋放的抑制劑。IC50&TargetIC50:1μM(neutralsphingomyelinase)[1]體外研究GW4869(10μM)partiallyinhibitsTNF-inducedsphingomyelin(SM)hydrolysis,and20μMofthecompoundiprotectedcompletelyfromthelossofSM.Theadditionof10-20μMGW4869completelyinhibitstheinitialaccumulationofceramide,whereasthiseffectispartiallylostatlatertimepoints(24h).TheactionofGW486occursdownstreamofthedropinglutathione.GW4869isable,inadose-dependentmanner,tosignificantlyprotectfromcelldeath[1].GW4869(10or20μM)inhibitsbothexosomereleaseandpro-inflammatorycytokineproductioninmacrophages.GW4869inhibitstheceramide-mediatedinwardbuddingofmultivesicularbodies(MVBs)andreleaseofmatureexosomesfromMVBs[2].GW4869alsocouldreversetheinhibitionofCCN23’-UTRactivitybymiR-214-enrichedexosomesinhepaticstellatecells[3].1/4www.MedChemEwww.MedChemESolutionAttention:GW4869isroutinelystoredat?80?°CasastocksuspensioninDMSO.CellViabilityAssay[1]CellLine:MCF7humanbreastcancercells.Concentration:10-20μM.IncubationTime:30min(thentreatedwithTNF(3nM)followed).Result:SignificantlyinhibitedTNF-inducedSMhydrolysis,whereas20μMofthecompoundprotectedcompletelyfromthelossofSM.CellViabilityAssay[2]CellLine:FreshRAW264.7macrophages.Concentration:10or20μM.IncubationTime:2hours(thentreatedwith1μg/mLLPSincubation).Result:LPS-triggeredexosomegenerationwasremarkablyattenuatedinmacrophagesuponpretreatmentofmacrophageswith10μMGW4869,asevidencedbya22%reductionintheactivityofAChE.Suchattenuationwasfurtherenhancedbytreatmentwiththedoseof20μM.體內(nèi)研究GW4869(2.5μg/g,i.p.)causesinhibitionofexosomereleaseblocksLPS-stimulatedpro-inflammatorycytokinproductionandcardiacinflammationinmice.GW4869mitigatesLPS-causedmyocardialdysfunctionandimprovessurvivalinmice[2].GW4869(2.5μg/g,i.p.)blockstheproductionofpro-inflammatorycytokinesandcardiacinflammationinCLPmice[2].AnimalModel:10-12weeksoldMalewild-typeC57BL/6mice(Endotoxin-ChallengedMice)[2].Dosage:2.5μg/g.Administration:I.P.once(1hlater,followedbyani.p.injectionofLPS(25μg/g,100μL)).Result:Significantlydecreasedexosomelevelsby37%insera,comparedtolevelscollectedfromcontrolmice.At12hafterLPSinjection,thelevelsofcirculatingexosomeswereincreasesignificantlycomparedtoPBS-controls,asevidencedbya1.7-foldelevationintheAChEactivity.AnimalModel:10-12weeksoldMalewild-typeC57BL/6mice(CLPPolymicrobialSepsisModel)[2].Dosage:2.5μg/g.2/4www.MedChemEwww.MedChemEAdministration:I.P.once(beforeshamorCLPsurgery).Result:Decreasedexosomeconcentrationby33%comparedtomiceinjectedwithPBSinsham-surgerycontrols.CLP-stimulatedexosomereleasewassignificantlyinhibitedbypre-treatmentofCLPmicecomparedtoCLPmicepre-treatedwithPBS.戶使?本產(chǎn)品發(fā)表的科研?獻?AdvSci(Weinh).2020Sep24;7(21):2002518.?JExtracellVesicles.2021Feb;10(4):e12068.?JExtracellVesicles.2021Jan;10(3):e12056.?MolTher.2020Dec2;28(12):2605-2620.?CellRep.2021Jan5;34(1):108576.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LubertoC,etal.Inhibitionoftumornecrosisfactor-inducedcelldeathinMCF7byanovelinhibitorofneutralsphingomyelinase.JBiolChem.2002Oct25;277(43):41128-39.[2].EssandohK,etal.BlockadeofexosomegenerationwithGW4869dampensthesepsis-inducedinflammationandcardiacdysfunction.BiochimBiophysActa.2015Nov;1852(11):2362-71.[3].ChenL,etal.Integrinsandheparansulfateproteoglycansonhepaticstellatecells(HSC)arenovelreceptorsforHSC-derivedexosomes.FEBSLett.2016Dec;590(23):4263-4274.[4].NakamuraH,etal.SphingomyelinRegulatestheActivityofSecretoryPhospholipaseA2inthePlasmaMembrane.JCellBiochem.2015Sep;116(9):1898-907.McePdfHeight3/4www.MedChemEwww.MedChemE關(guān)注MCE中國公眾號，

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