JQAD1-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEJQAD1Cat.No.:HY-145765CASNo.:2417097-18-6分⼦式:C₄₈H₅₂F₄N₆O₉分⼦量:932.95作⽤靶点:PROTACs;HistoneAcetyltransferase;Apoptosis;Caspase;PARP作⽤通路:PROTAC;Epigenetics;Apoptosis;CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(107.19mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.0719mL5.3593mL10.7187mL5mM0.2144mL1.0719mL2.1437mL10mM0.1072mL0.5359mL1.0719mL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。BIOLOGICALACTIVITY⽣物活性JQAD1CRBN依赖的PROTAC，选择性靶向EP300进⾏降解。JQAD1抑制EP300表达和H3K27ac修饰。JQAD1诱导细胞凋亡(apoptosis)。JQAD1可⽤于癌症研究。体外研究JQAD1suppressesEP300expression,suppressestheH3K27acmodification,andinducesapoptosis,1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEmarkedbyPARP1cleavageincontrolKellyNBcells,butnotinCRBN-knockoutcells[1].JQAD1(0.5or1μM;6-96h)treatmentresultedinearlytime-dependentinductionofasub-G1peak,suggestiveofapoptoticcelldeathinKellyandNGPcells[1].JQAD1(1μM;12-36h)inducesKellyNBcellapoptosis[1].JQAD1(0.5μM;24h)-treatedcellsexhibitsupregulationoftheproapoptoticBH3-onlyeffectorsBIM,BID,andPUMAtogetherwiththeproapoptoticmediatorBAXanditsinhibitorsBCL2andMCL1[1].JQAD1(0.5and1μM;24h)disruptsMYCNexpression[1].JQAD1(0.5μM;24h)causeslossofH3K27acatchromatin[1].JQAD1(1.2nM-20μM;5days)hasbroadCRBN-dependentantineoplasticactivityacrosscancercelllines[1].JQAD1inducesEP300degradationinatime-dependentmannerasearlyas16hours[1].WesternBlotAnalysis[1]CellLine:MYCN-amplifiedNBcellsConcentration:0.1,0.5,1,3,5,and10µMIncubationTime:24hResult:Demonstratedadose-dependentdecreaseinEP300expressionalongwithaparallellossoftheH3K27acmodification.InducedselectivelossofEP300expressioncoincidentwithcleavageofPARP1,signalingtheonsetofapoptosis.WesternBlotAnalysis[1]CellLine:KellyNBcellsConcentration:1µMIncubationTime:12,24,and36hoursResult:Increasedtheexpressionofcleavedcaspase-3andcleavedPARP1inadose-dependentmanner.体内研究JQAD1(40mg/kg;i.p.;daily,for21d)inhibitstumorgrowthinNSGmicewithKellyNBcellxenografts[1].AnimalModel:NSGmicewithKellyNBcellxenografts[1]Dosage:40mg/kgAdministration:Intraperitonealinjection;daily,for21daysResult:Suppressedtumorgrowthandprolongedsurvival.AnimalModel:CD1mice[1]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:10mg/kgAdministration:Intraperitonealinjection(PharmacokineticAnalysis)Result:Hadahalf-lifeof13.3(±3.37SD)hoursinmurineserum,withaCmaxof7μmol/L.REFERENCES[1].DurbinAD,et,al.EP300SelectivelyControlstheEnhancerLandscapeofMYCN-AmplifiedNeuroblastoma.CancerDiscov.2022Mar1;12(3):730-751.McePdfHeightCaution:Producthasnotbeenfullyvalidated