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

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZotatifinCat.No.:HY-112163CASNo.:2098191-53-6Synonyms:eFT226分?式:C??H??N?O?分?量:487.55作?靶點(diǎn):EukaryoticInitiationFactor(eIF);SARS-CoV;Apoptosis作?通路:CellCycle/DNADamage;Anti-infection;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:200mg/mL(410.21mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0511mL10.2554mL20.5107mL5mM0.4102mL2.0511mL4.1021mL10mM0.2051mL1.0255mL2.0511mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥5mg/mL(10.26mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5mg/mL(10.26mM);ClearsolutionBIOLOGICALACTIVITY?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(jìn)eIF4A與5'-UTRs中具有識(shí)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(qiáng)效的抗病毒效果，通過(guò)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(xì)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,7.3

nM,6.6nM,4.4nM,4.2nM,4.6nM,7.9nM,11.2nMand11.8nM,respectively[1].Zotatifin(30μM-100μM;

3or24hours)resultsintranslationalregulationofoncogenicprotein,decreasesMYC,CCND3,BCL2and

MCL1proteinexpressionasatime-anddose-dependentmanner[1].Theanti-viralactivityofZotatifinis

demonstratedbyvariousassays:suchasTCID50assay,Plaqueassay,NP-stainingassay,etal[2].Zotatifin

(10nM,100nM,200nM,500nM,2μM,10μM;1or2hourspre-treatmentbeforevirusisolates)decreases

thedetectionoftheviralNPproteinandreducesviralinfectivityinaconcentration-dependentmatterinVero

E6cellscellsinfectedwithSARS-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;andMCLtumortypecells2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration: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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CellRep.2021Oct12;37(2):109806.?Viruses.2022,14(3),519.?Pharmaceuticals.2022,15(9),1086.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].PeggyA.Thompson,etal.PreclinicalEvaluationofeFT226,aNovel,PotentandSelectiveeIF4AInhibitorwithAnti-tumorActivityinB-cellMalignancies.[2].GordonDE,etal.ASARS-CoV-2proteininteractionmaprevealstargetsfordrugrepurposing.Nature.2020Apr30.McePdfHeight3/