GW4869-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGW4869Cat.No.:HY-19363CASNo.:6823-69-4分⼦式:C₃₀H₃₀Cl₂N₆O₂分⼦量:577.5作⽤靶点:Phospholipase作⽤通路:MetabolicEnzyme/Protease储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验0.1MHCL:<1mg/mL(ultrasonic;adjustpHto2withHCl)(insoluble)H2O:<0.1mg/mL(ultrasonic)(insoluble)DMSO:0.1mg/mL(0.17mM;Needultrasonic)请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。BIOLOGICALACTIVITY⽣物活性GW4869⾮竞争性的中性鞘磷脂酶(N-SMase)抑制剂，IC50值为1μM。GW4869外泌体合成/释放的抑制剂。IC50&TargetIC50:1μM(neutralsphingomyelinase)[1]体外研究GW4869(10μM)partiallyinhibitsTNF-inducedsphingomyelin(SM)hydrolysis,and20μMofthecompoundisprotectedcompletelyfromthelossofSM.Theadditionof10-20μMGW4869completelyinhibitstheinitialaccumulationofceramide,whereasthiseffectispartiallylostatlatertimepoints(24h).TheactionofGW4869occursdownstreamofthedropinglutathione.GW4869isable,inadose-dependentmanner,tosignificantlyprotectfromcelldeath[1].GW4869(10or20μM)inhibitsbothexosomereleaseandpro-inflammatorycytokineproductioninmacrophages.GW4869inhibitstheceramide-mediatedinwardbuddingofmultivesicularbodies(MVBs)and1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEreleaseofmatureexosomesfromMVBs[2].GW4869alsocouldreversetheinhibitionofCCN23’-UTRactivitybymiR-214-enrichedexosomesinhepaticstellatecells[3].SolutionAttention:GW4869isroutinelystoredat−80ꢀ°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-triggeredexosomegenerationwasremarkablyattenuatedinmacrophagesuponpre-treatmentofmacrophageswith10μMGW4869,asevidencedbya22%reductionintheactivityofAChE.Suchattenuationwasfurtherenhancedbytreatmentwiththedoseof20μM.体内研究GW4869(2.5μg/g,i.p.)causesinhibitionofexosomereleaseblocksLPS-stimulatedpro-inflammatorycytokineproductionandcardiacinflammationinmice.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(2.5μg/g,100μL)).Result:Significantlydecreasedexosomelevelsby37%insera,comparedtolevelscollectedfromcontrolmice.At12hafterLPSinjection,thelevelsofcirculatingexosomeswereincreasedsignificantlycomparedtoPBS-controls,asevidencedbya1.7-foldelevationintheAChEactivity.AnimalModel:10-12weeksoldMalewild-typeC57BL/6mice(CLPPolymicrobialSepsisModel)[2].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:2.5μg/g.Administration:I.P.once(beforeshamorCLPsurgery).Result:Decreasedexosomeconcentrationby33%comparedtomiceinjectedwithPBSinsham-surgerycontrols.CLP-stimulatedexosomereleasewassignificantlyinhibitedbypre-treatmentofCLPmicecomparedtoCLPmicepre-treatedwithPBS.户使⽤本产品发表的科研⽂献•AdvMater.2021Dec;33(49):e2103471.•NatCommun.2022Aug1;13(1):4461.•AdvSci(Weinh).2020Sep24;7(21):2002518.•JExtracellVesicles.2021Feb;10(4):e12068.•JExtracellVesicles.2021Jan;10(3):e12056.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.JCellBioch