GSK-3685032-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGSK-3685032Cat.No.:HY-139664CASNo.:2170137-61-6分?式:C??H??N?OS分?量:420.53作?靶點:DNAMethyltransferase作?通路:Epigenetics儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:25mg/mL(59.45mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3780mL11.8898mL23.7795mL5mM0.4756mL2.3780mL4.7559mL10mM0.2378mL1.1890mL2.3780mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.94mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.94mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.94mM);ClearsolutionBIOLOGICALACTIVITY?物活性GSK-3685032?種?時間依賴、?共價、可逆的DNMT1選擇性抑制劑，IC50=0.036μM。GSK-3685032誘導DNA甲化喪失、轉(zhuǎn)錄激活和癌細胞?長抑制[1]。IC50&TargetDNMT1[1]體外研究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?邊的抑制劑?師www.MedChemEConcentration:10-10000nMIncubationTime:4daysResult:Dose-dependentincreasedofCXCL11,IFI27,HLA-DQA1andMAGEA4followingtreatmentofMV4-11cells.WesternBlotAnalysis[1]CellLine:GDM-1cellsConcentration:3.2-10,000nMIncubationTime:2daysResult:InhibitedDNMT1proteinexpression體內(nèi)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