Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemENecrostatin-1Cat.No.:HY-15760CASNo.:4311-88-0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溶解性數據體外實驗DMSO:≥46mg/mL(177.38mM)掃描?維碼，*"≥"meanssoluble,butsaturationunknown.運?溶解?案計算器獲得適合您實驗體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.8561mL19.2805mL38.5609mL5mM0.7712mL3.8561mL7.7122mL10mM0.3856mL1.9280mL3.8561mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存?式和期限。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，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/salinewater2.Solubility:12.5mg/mL(48.20mM);Suspendedsolution;Needultrasonic請依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(9.64mM);Clearsolution1/3www.MedChemEwww.MedChemE此?案可獲得≥2.5mg/mL(9.64mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述3.體系中加?50μLTween-80，混合均勻；然后繼續加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(9.64mM);Clearsolution此?案可獲得≥2.5mg/mL(9.64mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶液中，混合均勻。BIOLOGICALACTIVITY?物活性Necrostatin-1(Nec-1)?種有效的壞死性凋亡(necroptosis)抑制劑，在Jurkat細胞中的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].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]2/3www.MedChemEwww.MedChemEAdministration8-10weekoldmaleC57BL/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?本產品發表的科研?獻?Nature.2020Apr;580(7803):386-390.?SignalTransductTargetTher.2020May8;5(1):51.?CellDeathDiffer.2021Jan;28(1):251-266.?RedoxBiol.2020Jan;29:101402.?Autophagy.2019Nov;15(11):1990-2001.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-DRP1pathwayregulatesNLRP3inflammasomeactivationfollowingsubarachnoidhemorrhage.ExpNeurol.2017Sep;295:116-124.McePdfH