Zotatifin-eFT226-DataSheet-生命科學(xué)試劑-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEZotatifinCat.No.:HY-112163CASNo.:2098191-53-6Synonyms:eFT226分?式:C??H??N?O?分?量:487.55作?靶點:EukaryoticInitiationFactor(eIF);SARS-CoV;Apoptosis作?通路:CellCycle/DNADamage;Anti-infection;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCOA.BIOLOGICALACTIVITY?物活性Zotatifin(eFT226)?種有效，選擇性和耐受性良好的eIF4A抑制劑。Zotatifin可促進eIF4A與5'-UTRs中具有識別序的特定mRNA序列結(jié)合(IC50=2nM)，并?擾eIF4F起始復(fù)合物的組裝。Zotatifin表現(xiàn)出強效的抗病毒效果，通過抑制SARS-CoV-2NPprotein?物合成，從?有效減少病毒傳染性(IC90=37nM)。Zotatifin誘導(dǎo)細胞凋亡(apoptosis)。IC50&TargetIC50:2nM(eIF4A)[1]IC90:37nM(NP-stainingassay)[2]體外研究Zotatifininducestheformationofastableternarycomplex[eIF4A-RNA-eFT226].ZotatifinincreasestheresidencetimeforeIF4A1bindstoanAGAGAGRNAsurface,theKdvaluesare0.021μMand8.0μM,respectivelyforeFT226presenceorabsence[1].Zotatifininhibitsinvitrotranslationasasequence-dependentmanner,theIC50valuesare1.5nM,13.8nM,92.5nM,and217.5nM,respectivelyinanMDA-MB-231celllinewithtransientlytransfectedAGAGAG,GGCGGC,CCGCCGandCAACAA5’-UTRs-containingsequences[1].Zotatifin(0.0001μM-1μM;72hours)inhibitstumorcellsgrowthasadose-dependentmanner.Itshowsapotentanti-proliferativeactivity(GI50[1].Zotatifin(0.0001μM-1μM;72hours)inhibitstumorcellgrowth,exhibitsGI50valuesforTMD8,SU-DHL-2,HBL1,Pfeiffer,SU-DHL-6,SU-DHL-10,VAL,Carnaval,U2973,Ramos,Jeko1,Mino,andRec-1cellsare4.1nM,3nM,5.6nM,3.7nM,5.3nM,7.3nM,6.6nM,4.4nM,4.2nM,4.6nM,7.9nM,11.2nMand11.8nM,respectively[1].Zotatifin(30μM-100μM;3or24hours)resultsintranslationalregulationofoncogenicprotein,decreasesMYC,CCND3,BCL2andMCL1proteinexpressionasatime-anddose-dependentmanner[1].Theanti-viralactivityofZotatifinisdemonstratedbyvariousassays:suchasTCID50assay,Plaqueassay,NP-stainingassay,etal[2].Zotatifin(10nM,100nM,200nM,500nM,2μM,10μM;1or2hourspre-treatmentbeforevirusisolates)decreases1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEthedetectionoftheviralNPproteinandreducesviralinfectivityinaconcentration-dependentmatterinVeroE6cellscellsinfectedwithSARS-CoV-2isolates[2].CellViabilityAssay[1]CellLine:MDA-MB-231tumorcellsConcentration:0.0001μM,0.001μM,0.01μM,0.1μM,1μMIncubationTime:72hoursResult:InhibitedcellgrowthwithaGI50of15nM,andF163Lmutantrescuedanti-proliferativeeffects.CellProliferationAssay[1]CellLine:DLBCL-ABC;DLBCL-GCB;Burkitt;andMCLtumortypecellsConcentration:0.0001μM,0.001μM,0.01μM,0.1μM,1μMIncubationTime:72hoursResult:InhibitedcellgrowthwithGI50valuesrangingfrom3nMto20nM.CellProliferationAssay[1]CellLine:TMD8andPfeifferDLBCLtumorcellsConcentration:30μM;100μMIncubationTime:3or24hoursResult:DecreasedMYC,CCND3,Bcl2,andMCL1proteinlevels.體內(nèi)研究Zotatifin(intravenousinjection;1mg/kg;14-22days)decreasestumorvolume,inhibitstheTMD8xenograft-bearing,HBL1xenograft-bearing,Pfeifferxenograft-bearing,SU-DHL-6xenograft-bearing,SU-DHL-10xenograft-bearingandRamos-bearinganimals’tumorgrowthaspercentageof97%,87%,70%,83%,37%and75%,respectively[1].Zotatifin(intravenousinjection;0.001mg/kg-1mg/kg;15days)inhibitsthegrowthofB-celllymphomaxenograftsandiswell-toleratedagainstB-celllymphomaxenograftmodelsinvivo[1].AnimalModel:B-celllymphomaxenograftmodel[1]Dosage:0.001mg/kg;0.1mg/kg;1mg/kgAdministration:Intravenousinjection;15daysResult:ShowedefficacyinB-celllymphomaxenograftmodels.REFERENCES2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE[1].PeggyA.Thompson,etal.PreclinicalEvaluationofeFT226,aNovel,PotentandSelectiveeIF4AInhibitorwithAnti-tumorActivityinB-cellMalignancies.[2].GordonDE,etal.ASARS-CoV-2proteininteractionmaprevealstargetsfordrugrepurposing.Nature.2020Apr30.Mce