I-BET151-dihydrochloride-GSK1210151A-dihydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEI-BET151dihydrochlorideCat.No.:HY-110106CASNo.:1883545-47-8Synonyms:GSK1210151Adihydrochloride分⼦式:C₂₃H₂₃Cl₂N₅O₃分⼦量:488.37作⽤靶点:EpigeneticReaderDomain作⽤通路:Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性I-BET151dihydrochloride(GSK1210151Adihydrochloride)⼀种BET溴结构域(BETbromodomain)抑制剂，抑制BRD4，BRD2和BRD3的pIC50分别为6.1，6.3和6.6[1][2]。IC50&TargetpIC50:6.1(BRD4),6.3(BRD2),6.6(BRD3)[1]体外研究I-BET151dihydrochloride(1μM;72hours)treatmentdisplaysthemajorityoflivecellsresidedintheG0phaseandcommensuratewithadose-andtime-dependentdecreaseincellproliferationandabrogationofbromodeoxyuridineincorporation[2].I-BET151dihydrochloride(100nM;72hours)causesasignificantdose-andtime-dependentdecreaseintheproportionofmyelomacellsinS/G2phase[2].CellViabilityAssay[2]CellLine:H929cellsConcentration:1μMIncubationTime:72hoursResult:DisplaysthemajorityoflivecellsresidedintheG0phaseandcommensuratewithadose-andtime-dependentdecreaseincellproliferationandabrogationofbromodeoxyuridineincorporation.CellProliferationAssay[2]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:H929cellsConcentration:100nMIncubationTime:72hoursResult:Causedasignificantdose-andtime-dependentdecreaseintheproportionofmyelomacellsinS/G2phase.体内研究I-BET151dihydrochloridedemonstrateslowbloodclearanceintherat(~20%liverbloodflow)andgoodoralsystemicexposurewhichresultedingoodoralbioavailability.Highclearanceisobservedinthedog(~95%liverbloodflow).Thesystemicexposureinthedogislow,resultinginapoororalbioavailabilityof16%.Thehighbloodclearanceindogcorrelateswellwiththehighintrinsicclearanceobservedindogmicrosomesandhepatocytes,whereasthelowintrinsicclearancesseeninratandmouse(mouseIVC1.6mL/min/g;CLb8mL/min/kg)correlatewithlowerinvivobloodclearancesinthesespecies.Duetothelowsystemicexposureobservedinthedog,I-BET151dihydrochlorideisinvestigatedinthemini-pigasapotentialsecondspeciesfortoxicologicalevaluationwhereitshowedlowclearance(~32%liverbloodflow)andgoodbioavailability(65%)[1].I-BET151dihydrochloride(30mg/kg;i.p.;dailyfor21days)-treatsmicehasfour-tofivefoldsmallermyelomatumorsandasignificantlyreducesrateoftumorsizedoublingthanvehicle-treatedmice[2].AnimalModel:Mice(modelofsubcutaneousmyeloma)[2]Dosage:50mg/kgAdministration:I.p.;dailyfor21daysResult:Reducedrateoftumorsizedoublingthanvehicle-treatedmice.户使⽤本产品发表的科研⽂献•NatBiomedEng.2018Aug;2(8):578-588.•CellStemCell.2021Sep2;28(9):1597-1613.e7.•Oncogene.2021Mar12.•CellSyst.2018Apr25;6(4):424-443.e7.•PLoSPathog.2020Mar24;16(3):e1008429.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SealJ,etal.IdentificationofanovelseriesofBETfamilybromodomaininhibitors:BindingmodeandprofileofI-BET151(GSK1210151A).BioorgMedChemLett.2012Apr15;22(8):2968-72.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[2].ChaidosA,etal.PotentantimyelomaactivityofthenovelbromodomaininhibitorsI-BET151andI-BET762.Blood.2014Jan30;123(5):697-705.McePdfHeightCaution:Producthasnotb