PROTAC-O4I2-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPROTAC-O4I2Cat.No.:HY-141881分⼦式:C₂₉H₂₉ClN₆O₅S分⼦量:609.1作⽤靶点:PROTACs;Apoptosis作⽤通路:PROTAC;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(410.44mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6418mL8.2088mL16.4177mL5mM0.3284mL1.6418mL3.2835mL10mM0.1642mL0.8209mL1.6418mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.41mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性PROTAC-O4I2⼀种靶向剪接因⼦3B1(SF3B1)的PROTAC。PROTAC-O4I2在K562细胞中诱导FLAG-SF3B1降解，IC50值为0.244μM。PROTAC-O4I2还诱导K562WT细胞凋亡(apoptosis)[1]。IC50&TargetCereblon体外研究PROTAC-O4I2introducesThalidomidetoubiquitinE3ligasecereblon(CRBN),whichselectivelydegradesSF3B1andinhibitstumorgrowthincells[1].PROTAC-O4I2degradesandinhibitsSF3B1inK562cells.PROTAC-O4I2exhibitsanti-proliferationeffectsonSF3B1WT,SF3B1OE,andSF3B1K700EcellswithIC50sof228,63,and90nM,respectively[1].PROTAC-O4I2inducesFLAG-SF3B1degradationinaconcentration-dependentmannerwithahalfmaximalinhibitoryconcentration(IC50)valueof0.244μMinK562cells[1].CellProliferationAssay[1]CellLine:K562controlcells(WT),cellsoverexpressingSF3B1(OE),andcellsexpressingSF3B1K700E(K700E)Concentration:1pM,0.1nM,10nM,1μM,100μMIncubationTime:72hoursResult:InK562WTcells,theparentalcompoundO4I2exhibitedamarginalanti-proliferationeffect(IC50>10μM).Incontrast,PROTAC-O4I2showedsignificantlyhighertoxicitywithanIC50of228nM,nearly3-foldlesspotentthanpladienolideB(IC50,76nM).CellsoverexpressingSF3B1WTwasslightlyresistanttopladienolideB(IC50,134nM),butmoresensitivetoPROTAC-O4I2(anIC50valueof63nM).ApoptosisAnalysis[1]CellLine:K562cellConcentration:1μMIncubationTime:48hResult:InducedcellularapoptosissincellsexpressingSF3B1WTorSF3B1K700E.体内研究PROTAC-O4I2(10μM)significantlyincreasessurvivalbyinterferencewiththemaintenanceandproliferationoftumorinaDrosophilaintestinaltumormodel[1].AnimalModel:Drosophilamelanogaster[1]Dosage:10μMAdministration:FlieswerefedonaroundfilterpaperloadedwithPROTAC-O4I2ina5%sucrose2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEsolution,maintainedat18℃andflippedintoafreshlypreparedvialevery2daysResult:Decreasedstemcellactivity,blockedtheinitiationandgrowthoftumor,andimprovedthesurvivaloftheDrosophilaISCtumormodel.REFERENCES[1].RodrigoAGama-Brambila,etal.APROTACtargetssplicingfactor3B1.CellChemBiol.2021Nov18;28(11):1616-1627.e8.McePdfHeightCaution:Producthasnotbeenfullyvali