Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEALK5-IN-34Cat.No.:HY-151289CASNo.:2785430-90-0分?式:C??H??N?O分?量:413.48作?靶點(diǎn):TGF-βReceptor;TGF-beta/Smad作?通路:TGF-beta/Smad;StemCell/Wnt儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性ALK5-IN-34?種選擇性的激活素受體樣激酶(ALK)抑制劑，具有?服活性。ALK5-IN-34可以抑制激活素受體樣激酶的活性，IC50值≤10nM。ALK5-IN-34還具有抑制腫瘤?長(zhǎng)的作?，可?于癌癥等增殖性疾病的研究。IC50&TargetALK550)體外研究ALK5-IN-34(EX-11)haskinaseinhibitionofALK5withanIC50valueof≤10nM[1].ALK5-IN-34haskinaseselectivityofALK2/ALK5withanIC50valueof＜100nM[1].ALK5-IN-34showsTGFB-RIinhibition(RD-SMADreceptoractivity)withanIC50valueof≤100nM[1].ALK5-IN-34(1μM-10nM)inhibitstheexpressionofTGF-β-mediatedalpha-SMAinafullconcentration-dependent[1].ALK5-IN-34(30,300and3000nM)suppressestheTregfrequencyinadosedependentmanner[1].ALK5-IN-34(0-0.1μM;for6daysor7days)inhibitsFOXL2CI34W-drivengrowthinKGNandCOV434cellswithIC50valuesof140nMand﹥10μM,respectively[1].ALK5-IN-34(10,100and1000nM;2h)showsadose-dependentdecreaseinpSmad2inKGNcellline[1].ALK5-IN-34(30,300nM;24h)reversestheupregulationofgeneexpressionindosedependentent[1].ALK5-IN-34(30,300nM;24h)increasesHLAclassIexpressionindose-dependent[1].CellViabilityAssay[1]CellLine:KGNandCOV434celllines1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:0-0.1μMIncubationTime:for6daysor7daysResult:InhibitedFOXL2CI34W-drivengrowth.RT-PCR[1]CellLine:HumanprimarydermalfibroblastsConcentration:30,300nMIncubationTime:24hResult:ReversedtheupregulationofgeneexpressionwithTGFBstimulation.體內(nèi)研究ALK5-IN-34(EX-11)(oral;10-100mg/kg)reducesthephophoSMAD2levels(p-SMAD2)inadosedependentmannerinA549murinexenograftmodel[1].ALK5-IN-34(oral;75mg/kg;0-24h)showsreverselycorrelatedbetweenPKandtumorPD(pSMAD2levels)[1].ALK5-IN-34(oral;150mg/kg;bid;for22days)increasesoverallsurvivalinES-2ovariancancermousexenograftmodelandcandelayprogression[1].ALK5-IN-34(p.o.;75,150mg/kg;twiceaday;for21days)showstumorgrowthinhibition(TGI)andincreasesthesurvivalwhencombiningwithanti-PD-L1/anti-PD-1inSyngeneicTNBCModelandinSubcutaneousCloudmanS91melanomamodel[1].ALK5-IN-34(oral;300,1000mg/kg;bidfor5days)hasgoodtolerabilityandsafetymargininTolerabilityModel[1].AnimalModel:A549murinexenograftmodel[1]Dosage:10,50,75and100mg/kgAdministration:oralgavageResult:Exhibited92.5%inhibitionbasedupontheaveragep-SMAD2levels(75mg/kg).AnimalModel:EMT6SyngeneicTNBCModel[1]Dosage:75,150mg/kgAdministration:p.o.,twiceaday,for21daysResult:Resultedsignificantlytumorgrowthinhibition(TGI)by37%at150mg/kg.Resultinsignificanttumorgrowthinhibition(TGI)withcombinationofanti-PD-LIandresultedinasignificantincreaseinmeansurvivalby37%.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResultedinsignificantTGIby34%withcombinationofanti-PD-1andresultedinsignificantincreaseinmeansurvivalby26%.Decreasedtheintra-tumoralpressure.AnimalModel:CachexiaModel[1]Dosage:150mg/kgAdministration:oralgavage,twiceadayfor22daysResult:Showedreductionintotalfluidvolumeandhighwholelimbweights.REFERENCES[1].BettinaFRANZ,etal.Alk-5inhibitorsandusesthereof.Patent.WO2022126133A1.McePdfHeightCaution:Producthas