Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemE4EGI-1Cat.No.:HY-19831CASNo.:315706-13-9分?式:C??H??Cl?N?O?S分?量:451.28作?靶點:EukaryoticInitiationFactor(eIF);Autophagy;Apoptosis作?通路:CellCycle/DNADamage;Autophagy;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥35mg/mL(77.56mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2159mL11.0796mL22.1592mL5mM0.4432mL2.2159mL4.4318mL10mM0.2216mL1.1080mL2.2159mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?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(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)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(xiàn)沉淀、析出現(xiàn)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：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:2.5mg/mL(5.54mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性4EGI-1?種eIF4E/eIF4G相互作?抑制劑，抑制eIF4E結(jié)合，Kd值為25μM。IC50&TargetKd:25μM(eIF4E/eIF4G)[1]體外研究4EGI-1isaninhibitorofeIF4E/eIF4Ginteraction,withaKdof25μMagainsteIF4Ebinding.4EGI-1disruptstheeIF4Fcomplexandinhibitsexpressionofoncogenicproteinsinmammaliancells.4EGI-1(0-40μM)alsoexhibitsproapoptoticactivityandinhibitsthegrowthofmultiplecancercelllines[1].4EGI-1iscytotoxictobreastcancercells,suchasSKBR-3,MCF-7andMDA-MB-231cells,withtheIC50ofappr30μM,andtothenon-CSCs(Cancerstemcells),theIC50isabout22μM.4EGI-1enhancesbreastCSCdifferentiation(40μM),andsuppressesbreastCSCinducedHUVECtube-likestructureformation(8μM).Moreover,4EGI-1selectivelyinhibitstranslationthatpersistsinCSCmaintenanceanddissemination[2].4EGI-1(50μM)impairstheformationofeIF4FcomplexinU87cells.4EGI-1(10,50and100μM)inhibitscellproliferationviainducingapoptosisinU87cells,andtheapoptosisisviaBaxactivation.4EGI-1causesmitochondrialdysfunction,andinducesERstressviaGRP-78activation,inU87cells[3].體內(nèi)研究4EGI-1(75mg/kg,i.p.)inhibitsbreastcancerstemcells(CSC)tumorgrowthandtumorangiogenesisinvivo[2].4EGI-1(75mg/kg,i.p.)showsinhibitoryeffectonthetumorvolumeandweightinmicebearingU87cells[3].PROTOCOLCellAssay[2]1×104breastCSCsHMLER(CD44high/CD24low)FAcellsandotherindicatedbreastcancercellsaretreatedwithDMSO,or[E]-4EGI-1or[Z]-4EGI-1atseriesofconcentrationsfor24hours.Thecellsareperformedcellviabilityassayswithcellviabilityassaykit.Threeindependentexperimentsareperformed.AverageIC50resultsareshown(mean±SD,t-test,two-tailed)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]Inthetumorxenograftedassay,1×105breastcancerstemcells(CSCs)aremixedwith100μLMatrigel/DMEMmixture(Matrigel:DMEM=1:2).BreastCSCs/Matrigel/DMEMmixturesareinjectedintoNOD/SCIDfemalemicemammaryglandsbysubcutaneousinjection.Afterthetumorformation(about75mm3involume,5mice/group),DMSO,or75mg/kg[E]-4EGI-1,or75mg/kg[Z]-4EGI-1isinjectedintothemicebyintraperitonealinjectiondailyfor30days.Tumorvolumesaremeasuredeverythreedays.Atthe30thday,micearesacrificedandtumorsareexcised.Tumorsweightsaremeasured.Tumortissuesamplesareusedforimmunohistostaining,Westernblotandimmunoprecipitationanalyses[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?NucleicAcidsRes.2022Jul18;gkac611.?NatCommun.2017Jun8;8:15617.?SciAdv.2022Jun24;8(25):eabo1782.?CellDeathDis.2020Nov15;11(11):982.?MolCancerTher.2018Dec;17(12):2676-2688.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MoerkeNJ,etal.Small-moleculeinhibitionoftheinteractionbetweenthetranslationinitiationfactorseIF4EandeIF4G.Cell.2007Jan26;128(2):257-67.[2].YiT,etal.4EGI-1targetsbreastcancerstemcellsbyselectiveinhibitionoftranslationthatpersistsinCSCmaintenance,proliferationandmetastasis.Oncotarget.2014Aug15;5(15):6028-37.[3].WuM,etal.Anti-CancerEffectofCap-TranslationInhibitor4EGI-1inHumanGliomaU87Cells:InvolvementofMitochondrialDysfunctionandERStress.CellPhysiolBiochem.2016;40(5):1013-1