Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENecrostatin-1Cat.No.:HY-15760CASNo.:4311-88-0Synonyms:Nec-1分?式:C??H??N?OS分?量:259.33作?靶點:RIPkinase;Autophagy;Indoleamine2,3-Dioxygenase(IDO);Ferroptosis作?通路:Apoptosis;Autophagy;MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥46mg/mL(177.38mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.8561mL19.2805mL38.5609mL5mM0.7712mL3.8561mL7.7122mL10mM0.3856mL1.9280mL3.8561mL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儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：0.5%CMC-Na/salinewaterSolubility:12.5mg/mL(48.20mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%(50%EtOH>>50%CremophorEL)>>90%salineSolubility:1.67mg/mL(6.44mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(9.64mM);Clearsolution4.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(9.64mM);ClearsolutionBIOLOGICALACTIVITY?物活性Necrostatin-1(Nec-1)?種有效的能透過?腦屏障的壞死性凋亡(necroptosis)抑制劑，在Jurkat細(xì)胞中的EC50為490nM。Necrostatin-1抑制RIP1激酶(EC50=182nM)。Necrostatin-1(Nec-1)也?種(IDO)抑制劑。IC50&TargetEC50:182nM(RIP1kinase)[1]體外研究Necrostatin-1(Nec-1)efficientlyinhibitstheTNFα-inducednecroticdeathofL929cells,whichdoesnotrequireexogenouscaspaseinhibitors[1].Necrostatin-1(Nec-1)preventsradiocontrastmedia(RCM)-induceddilationofperitubularcapillaries,suggestinganovelroleunrelatedtocelldeathfortheRIP1kinasedomainintheregulationofmicrovascularhemodynamicsandpathophysiologyofcontrast-inducedAKI(CIAKI)[2].Necrostatin-1(Nec-1)(30μM)increasesthesurvivalofcardiomyocyteprogenitorcell(CMPCs)byinhibitingnecroticcelldeath[4].體內(nèi)研究Necrostatin-1(Nec-1)inducestubularbilationandaffectsthekineticsofthedilationofperitubularcapillariesafterRCMapplication.UponasingleintraperitonealapplicationofasingledoseofNecrostatin-1(1.65mg/kgbodyweight,i.p.)15minutesbeforeRCM,thereturntobaselinelevelsispreventedwithintheobservationperiod[2].PROTOCOLCellAssay[3]C6(3×105cells/well)andU87(1.5×105cells/well)gliomacellsareseededonto96-wellmicroplateandcultured24h.PBSisaddedintothecontrolgroupandShikoninisaddedintoexperimentalgrouptoreachthefinalconcentration.CellularviabilityisassessedusinganMTTassayafterShikonintreatmentatindicatedtimepoint.Theabsorbancevalue(A)at570nmisreadusinganautomaticmulti-wellspectrophotometer.TwogroupsofgliomacellsfromthesamecelllinearetreatedwithShikoninatlowerorhigherconcentration,respectively;othertwogroupsofgliomacellsaretreated1hwith100μMNecrostatin-1or40μMz-VAD-fmkpriortoco-incubationwithShikoninatindicatedconcentration.Additionally,anothertwogroupsofgliomacellsaretreatedonlywith100μMNecrostatin-1or40μMZ-VAD-fmkatcorrespondingtimepoint[3].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration8-10weekoldmaleC57BL/6mice(averageweightapprox.23g)areused.Micereceiveintravenousapplicationof200μLPBSorradiocontrastmedia(RCM)viathetailvein.AsingledoseofZ-VAD-fmk(10mg/kgbodyweight)orNecrostatin-1(1.65mg/kgbodyweight)isappliedintraperitoneally15min.beforeRCM-injection.Miceareharvestedanother24hoursafterRCM-application(48hoursafterreperfusion).Bloodsamplesareobtainedfromretroorbitalbleedingandserumlevelsofureaandcreatininearedetermined.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Nature.2020Apr;580(7803):386-390.?Circulation.2022Nov30.?SignalTransductTargetTher.2020May8;5(1):51.?BioactMater.2021Nov19;13:23-36.?ActaPharmSinB.2021Dec;11(12):3966-3982.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DegterevA,etal.Chemicalinhibitorofnonapoptoticcelldeathwiththerapeuticpotentialforischemicbraininjury.NatChemBiol.2005Jul;1(2):112-9.[2].LinkermannA,etal.TheRIP1-kinaseinhibitornecrostatin-1preventsosmoticnephrosisandcontrast-inducedAKIinmice.JAmSocNephrol.2013Oct;24(10):1545-57.[3].HuangC,etal.ShikoninkillsgliomacellsthroughnecroptosismediatedbyRIP-1.PLoSOne.2013Jun28;8(6):e66326.[4].FeyenD,etal.Increasingshort-termcardiomyocyteprogenitorcell(CMPC)survivalbynecrostatin-1didnotfurtherpreservecardiacfunction.CardiovascRes.2013Jul1;99(1):83-91.[5].ZhouK,etal.RIP1-RIP3-DRP1pathwayregulatesNLRP3inflammasomeactivationfollowingsu