BRD4-CK2-IN-1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBRD4/CK2-IN-1Cat.No.:HY-145260分⼦式:C₂₉H₃₀ClN₅O₅分⼦量:564.03作⽤靶点:EpigeneticReaderDomain;CaseinKinase;Apoptosis;Autophagy作⽤通路:Epigenetics;CellCycle/DNADamage;StemCell/Wnt;Apoptosis;Autophagy储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性BRD4/CK2-IN-1⼀种⾸次⾼效、⼝服有效的BRD4/CK2(含溴结构域蛋⽩4/酪蛋⽩激酶2)双靶点抑制剂。BRD4/CK2-IN-1对BRD4和CK2的IC50值分别为180nM和230nM。BRD4/CK2-IN-1具有很强的抗癌活性，且⽆明显毒性。BRD4/CK2-IN-1在三性乳腺癌(TNBC)中诱导细胞凋亡和⾃噬相关的细胞死亡[1]。IC50&TargetBRD4CK2180nM(IC50)230nM(IC50)体外研究BRD4/CK2-IN-1(compound44e)(0-25μM;24hours)hasanti-proliferationeffectwithIC50sof2.66and3.52μMinMDA-MB-231andMDA-MB-468cells,respectively[1].BRD4/CK2-IN-1(0-10μM;24hours)dose-dependentlyinducesapoptosisofMDA-MB-231andMDA-MB-468cells[1].BRD4/CK2-IN-1(0-10μM;24hours)dose-dependentlydownregulatesBcl-2butupregulatesBaxandcleavedcaspase-3[1].BRD4/CK2-IN-1(0-10μM;24hours)significantlydownregulatestheautophagysubstratep62andup-regulatedbeclin-1andLC3IIinMDA-MB-231andMDA-MB[1].CellViabilityAssay[1]CellLine:MDA-MB-231,MDA-MB-468cellsConcentration:0,0.19,0.39,0.78,1.56,3.13,6.25,12.5,25ꢀμMIncubationTime:24hours1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Showedanti-proliferativeratesinMDA-MB-231andMDA-MB-468cells(IC50=2.66and3.52μM,respectively).ApoptosisAnalysis[1]CellLine:MDA-MB-231,MDA-MB-468cellsConcentration:0,2.5,5,10μMIncubationTime:24hoursResult:Dose-dependentlyinducedapoptosisofMDA-MB-231andMDA-MB-468cells.WesternBlotAnalysis[1]CellLine:MDA-MB-231,MDA-MB-468cellsConcentration:0,2.5,5,10μMIncubationTime:24hoursResult:Dose-dependentlydownregulatedBcl-2butupregulatedBaxandcleavedcaspase-3.CellLine:Concentration:IncubationTime:Result:体内研究BRD4/CK2-IN-1(25and50mg/kg;intragastricadministration;dailyfor19days)inhibitstumorgrowthinTNBCxenograftmodels[1].BRD4/CK2-IN-1(25and50mg/kg;intragastricadministration;dailyfor19days)showsweaktoxicitymeasuredbybodyweightlossintheMDA-MB-231andMDA-MB-468xenograftmodels[1].PreliminaryAssessmentofPharmacokinetics(PK)profileofBRD4/CK2-IN-1[1].Parameteriv(1mg/kg)po(10mg/kg)T1/2(h)4.21±0.575.14±0.71Cmax(ng/mL)237±11206±6AUC0-t(ng·h/mL)579±492079±130AUC0-∞(ng·h/mL)588±362090±146VZ(L/kg)21.1±2.6CL((mL/min)/kg)57.4±1.3F(%)32.5AnimalModel:Femalenudemice(BALB/c,6-8weeks,20-22g)bearingMDA-MB-231cells[1]Dosage:25and50mg/kgAdministration:Intragastricadministration;dailyfor19days2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Hadthemostpronouncedtumorgrowthinhibition(TGI)(63.8%)intheMDA-MB-231xenografttumormodelat50mg/kg.REFERENCES[1].ZhangJ,etal.DiscoveryofNovelDual-TargetInhibitorofBromodomain-ContainingProtein4/CaseinKinase2InducingApoptosisandAutophagy-AssociatedCellDeathforTriple-NegativeBreastCancerTherapy.JMedChem.2021;64(24):18025-18053.McePdfHeightCaution:Producthasnotbeenfullyvali