E64FC26-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEE64FC26Cat.No.:HY-122895CASNo.:2285446-62-8分?式:C??H??F?O?分?量:340.38作?靶點(diǎn):Apoptosis作?通路:Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(293.79mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.9379mL14.6895mL29.3789mL5mM0.5876mL2.9379mL5.8758mL10mM0.2938mL1.4689mL2.9379mL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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?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(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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)Solubility:≥2.5mg/mL(7.34mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性E64FC26蛋?質(zhì)?硫鍵異構(gòu)酶(PDI)家族的?種有效的泛抑制劑，對PDIA1、PDIA3、PDIA4、TXNDC5和PDIA6的IC50分別為1.9、20.9、25.9、16.3和25.4μM。E64FC26顯?抗?髓瘤活性。體外研究E64FC26(0.01-100μM;24hours)showsanti-MMactivity,withanEC50of0.59μM[1].E64FC26ismorecytotoxicagainstageneticallydiversepanelofmultiplemyeloma(MM)celllines(KMS11,OPM2,MM.1SBzR,MM.1S,SA-13,U266BzR,ANBL6,KMS12PE,U266,8226DxR,8226BzR,KMS12BM,H929,8226cells)whencomparedtonon-malignantcells[1].CellViabilityAssay[1]CellLine:MM.1SBzRcellsConcentration:0.01,0.1,1,10,100μMIncubationTime:24hoursResult:Showedanti-MMactivity,withanEC50of0.59μM.體內(nèi)研究E64FC26(2mg/kg;i.p.;threedaysaweekfor7days)showsanti-MMeffectinNSGmicemodel,andincreasesmediansurvivalby2weeks[1].ThecombinationofE64FC26andBortezomibproducedthegreatestimprovementinsurvival,extendingthemediansurvivalby20days[1].PharmacokineticofE64FC26wasmeasuredinCD-1mice.E64FC26wasadministeredi.v.(2mg/kg;graytracing)orp.o.(5mg/kg;bluetracing)andplasmadrugconcentrationsweremeasuredovera24hperiod.InCD-1micedemonstratedadequateoralbioavailabiltyof34%withsystemicexposureapproachingamaximumconcentration(Cmax)of400nMafterasingleoraldoseof5mg/kgwithaterminalhalf-lifeof9.5h[1].Vk*MYCtransgenicmicearetreatedwithE64FC26(2mg/kg,i.p.,3days/week)fortwoconsecutiveweeks.E64FC26treatmentinducesanimmediateanti-MMresponse,decreasingserumM-proteininallmicebyanaverageof33±7.9%[1].AnimalModel:NOD-SCIDIL2Rγ-/-(NSG)mice(bearingMM.1Scells)[1]Dosage:2mg/kgAdministration:i.p.;threedaysaweekfor7daysResult:Showedaclearanti-MMeffectinthismodelalso,increasingmediansurvivalby2weeks.REFERENCES[1].RobinsonRM,etal.Inhibitorsoftheproteindisulfideisomerasefamilyforthetreatmentofmultiplemyeloma.Leukemia.20192/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEApr;33(4):1011-1022.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor