GSK-3685032-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGSK-3685032Cat.No.:HY-139664CASNo.:2170137-61-6分⼦式:C₂₂H₂₄N₆OS分⼦量:420.53作⽤靶点:DNAMethyltransferase作⽤通路:Epigenetics储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1monthBIOLOGICALACTIVITY⽣物活性GSK-3685032⼀种⾮时间依赖、⾮共价、可逆的DNMT1选择性抑制剂，IC50=0.036μM。GSK-3685032诱导DNA甲化丧失、转录激活和癌细胞⽣长抑制[1]。IC50&TargetDNMT1[1]体外研究GSK-3685032(6days)hascellgrowthinhibitionofmajoritycancercelllines,withamediangrowthIC50valueof0.64μM[1].GSK-3685032(0.1-1000nM,1-6days)exhibitsgrowthinhibitionafter3days,withdecreasinggrowthIC50throughouta6dtimecourse[1].GSK3685032(10-10000nM,day4)dose-dependentlyincreasestheimmune-relatedgenetranscription[1].GSK3685032(3.2-10,000nM,2days)inhibitsDNMT1proteinexpression[1].GSK3685032inducesDNAhypomethylationandgeneactivation[1].CellProliferationAssay[1]CellLine:15leukemia,29lymphomaand7multiplemyelomacelllines,e.g.,EOL-1,Ki-JK,MM.IRcells.Concentration:0.01-100μMIncubationTime:6days1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Showedcellgrowthinhibitionofmajoritycancercelllines,withamediangrowthIC50valueof0.64μM.CellProliferationAssay[1]CellLine:MV4-11cellsConcentration:0.1-1000nMIncubationTime:1-6daysResult:Exhibitedgrowthinhibitionafter3days,withdecreasinggrowthIC50throughouta6dtimecourse.RT-PCR[1]CellLine:MV4-11cellsConcentration:10-10000nMIncubationTime:4daysResult:Dose-dependentincreasedofCXCL11,IFI27,HLA-DQA1andMAGEA4followingtreatmentofMV4-11cells.WesternBlotAnalysis[1]CellLine:GDM-1cellsConcentration:3.2-10,000nMIncubationTime:2daysResult:InhibitedDNMT1proteinexpression体内研究GSK-3685032(1-45mg/kg;subcutaneoustwicedailyfor28days)inhibitstumorgrowthinthesubcutaneousMV4-11orSKM-1xenograftmodels[1].SummaryofmousepharmacokineticparametersforGSK-3685032[1]Dose,RouteCmax(ng/mL)AUC0-8hr(h*ng/mL)DNAUC(h*kg*ng/mL/mg)Clearance(mL/min/kg)Volumedss(L/kg)T1/2(h)2mg/kg,IV510324181209131.31.82mg/kg,SC252921461NANA2.82mg/kg,SC547315400513NANANDAnimalModel:MV4-11xenograftmodels(femaleCD1-Foxn1mice,12weeksofage)orSKM-1xenograftmodels(NOD.CB17-Prkdc1NCrCrlmice,8-11weeksofage)[1]Dosage:1,5,15,30,45mg/kg(10%captisoladjustedtopH4.5-5with1Maceticacid,storedfor2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEupto1weekat4°C)Administration:Subcutaneousinjection,twicedailyfor4weeksResult:Revealedstatisticallysignificantdose-dependenttumorgrowthinhibitionwithclearregressionat≥30mg/kg.REFERENCES[1].PappalardiMB,etal.Discoveryofafirst-in-classreversibleDNMT1-selectiveinhibitorwithimprovedtolerabilityandefficacyinacutemyeloidleukemia.NatCancer.2021;2(10):1002-1017.McePdfHeightCaution:Producthasnotbeenfullyvalidatedforme