I-BET151-dihydrochloride-GSK1210151A-dihydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEI-BET151dihydrochlorideCat.No.:HY-110106CASNo.:1883545-47-8Synonyms:GSK1210151Adihydrochloride分?式:C??H??Cl?N?O?分?量:488.37作?靶點(diǎn):EpigeneticReaderDomain作?通路:Epigenetics儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性I-BET151dihydrochloride(GSK1210151Adihydrochloride)?種BET溴結(jié)構(gòu)域(BETbromodomain)抑制劑，抑制BRD4，BRD2和BRD3的pIC50分別為6.1，6.3和6.6[1][2]。IC50&TargetpIC50:6.1(BRD4),6.3(BRD2),6.6(BRD3)[1]體外研究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?邊的抑制劑?師www.MedChemECellLine:H929cellsConcentration:100nMIncubationTime:72hoursResult:Causedasignificantdose-andtime-dependentdecreaseintheproportionofmyelomacellsinS/G2phase.體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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?邊的抑制劑?師www.MedChemE[2].ChaidosA,etal.PotentantimyelomaactivityofthenovelbromodomaininhibitorsI-BET151andI-BET762.Blood.2014Jan30;123(5):697-705.McePdfHeightCaution:Producthasnotb