Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemERIPK1-IN-34Cat.No.:HY-178464CASNo.:3065634-19-4分子式:C??H??N?O?分子量:491.54作用靶點(diǎn):RIPkinase;MixedLineageKinase;Necroptosis作用通路:Apoptosis;MAPK/ERKPathway儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 RIPK1-IN-34是一種選擇性、可穿透血腦屏障的RIPK1抑制劑(IC50=126.70nM)，對RIPK3幾乎沒有抑制作用(IC50＞10,000nM)。RIPK1-IN-34通過抑制壞死性凋亡(necroptosis)通路中RIPK1、RIPK3和混合譜系激酶結(jié)構(gòu)域樣假激酶(MLKL)的磷酸化，發(fā)揮顯著的神經(jīng)保護(hù)作用。RIPK1-IN-34在大鼠大腦中動脈閉塞(MCAO)模型中顯示出神經(jīng)保護(hù)作用。RIPK1-IN-34可用于急性缺血性卒中(AIS)的治療研究[1]。IC50&TargetRIPK1126.7nM(IC50)體外研究RIPK1-IN-34(Compound9b)significantlyreducesTNF-α(T),aSmac-mimetic,SM-164(HY-15989)(S),andZ-VAD-FMK(HY-16658B)(Z)-inducedapoptosisinHT-29(EC50=71.61nM)andHT-22(EC50=38.45nM)cells[1].RIPK1-IN-34(0.78-400nM,24h)effectivelycounterstheTSZ-inducedchangesandapproximatestheuntreatedcontrolgroup'sconditioninHT-29,U937,L929andHT-22cells[1].RIPK1-IN-34(1,10,100nM,4.5h)iseffectiveinprotectingthecellsfromnecroptosisinL929cells[1].CompoundRIPK1-IN-34(0-1000nM,4.5h)dose-dependentlyinhibitsthephosphorylationofRIPK1,RIPK3,andMLKLinL929cells[1].ApoptosisAnalysis[1]CellLine:L929cellsConcentration:1nM,10nM,100nMIncubationTime:Afterpre-incubationwiththecompoundfor30minutes,cellsweretreatedwithTSZfor41/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEhoursResult:EffectivelyprotectedthecellsfromnecroptosisinL929cells.WesternBlotAnalysis[1]CellLine:L929cellsConcentration:0nM,10nM,100nM,1000nMIncubationTime:Afterpre-incubationwiththecompoundfor30minutes,cellsweretreatedwithTSZfor4hoursResult:Decreasedtheintensitiesofp-RIPK1andp-RIPK3bandsinresponsetoincreasingconcentrations.CurtailedtheenhancementofMLKLphosphorylation.體內(nèi)研究RIPK1-IN-34(Compound9b)(0.5-4.5mg/kg,i.v.,twice)dose-dependentlyimprovesneurologicalfunction,reducescerebralinfarctionvolume,andinhibitsinflammationandoxidativestressinSDrats,demonstratingitssignificantneuroprotectiveeffect[1].RIPK1-IN-34(78.4-160mg/kg,i.p.,twointraperitonealinjections,onehourapart)doesnotcauseacutetoxicityatthedosetestedinC57BL/6mice,anditsLD50exceeds160mg/kg,indicatingthatithasahighsafetyprofile[1].AnimalModel:SPFgrademaleSDrats(180-200g)wereusedtoconstructamiddlecerebralocclusionmodel[1].Dosage:0.5mg/kg,1.5mg/kg,4.5mg/kgAdministration:I.v.,administeredintravenouslyonce0.5hoursbeforemodeling,andagainafterreperfusion,foratotaloftwoadministrationsResult:Significantlyimprovedneurologicaloutcomes24hpost-operation,withreductionsinscoresexhibitingadose-dependenttrend:lowdose(5.20),mediumdose(5.09),andhighdose(3.82).Significantlyreducedinfarctvolumesacrossalltreatmentgroupsinadose-responsivemanner:lowdose(20.60),mediumdose(18.32),andhighdose(16.51).DiminishedMDA,TNF-α,andIL-1βlevelswhileslightlyincreasingSODlevels.AnimalModel:SPFgrademaleC57BL/6mice(aged6-8weeks,weighing18-22g)[1].Dosage:160mg/kg,112mg/kg,78.4mg/kgAdministration:I.p.,twointraperitonealinjections,onehourapart2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult: Noabnormalbehaviorsordeathswereobserved,andthebodyweightofmiceinallgroupssteadilyincreasedover7dayswithnosignificantdifferences.REFERENCESSuR,etal.Design,synthesis,anti-acuteischemicstroke(AIS)effectofreceptor-interactingproteinkinase1(RIPK1)inhibitorscontainingquinazolinestructure.BioorgChem.2025Oct;165:109013.McePdfHeightCaution:Pro