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°C1month溶解性数据体外实验DMSO:25mg/mL(59.45mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3780mL11.8898mL23.7795mL5mM0.4756mL2.3780mL4.7559mL10mM0.2378mL1.1890mL2.3780mL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。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.94mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.94mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.94mM);ClearsolutionBIOLOGICALACTIVITY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:6daysResult:Showedcellgrowthinhibitionofmajoritycancercelllines,withamediangrowthIC50valueof0.64μM.CellProliferationAssay[1]CellLine:MV4-11cellsConcentration:0.1-1000nMIncubationTime:1-6daysResult:Exhibitedgrowthinhibitionafter3days,withdecreasinggrowthIC50throughouta6dtimecourse.RT-PCR[1]CellLine:MV4-11cells2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration: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,storedforupto1weekat4°C)Administration:Subcutaneousinjection,twicedailyfor4weeksResult:Revealedstatisticallysignificantdose-dependenttumorgrowthinhibitionwithclearregressionat≥30mg/kg.REFERENCES[1].PappalardiMB,etal.Discoveryofafirst-in-classreversibleDNMT1-selectiveinhibitorwithimprovedtolerabilityandefficacyinacutemyeloidleukemia.NatCancer.2021;2(10):1002-1017.McePdfHeightCaution:P