SGI-1027-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESGI-1027Cat.No.:HY-13962CASNo.:1020149-73-8分⼦式:C₂₇H₂₃N₇O分⼦量:461.52作⽤靶点:DNAMethyltransferase;Apoptosis作⽤通路:Epigenetics;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:27mg/mL(58.50mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1668mL10.8338mL21.6675mL5mM0.4334mL2.1668mL4.3335mL10mM0.2167mL1.0834mL2.1668mL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(5.42mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—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(5.42mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.42mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性SGI-1027DNA甲转移酶(DNMT)抑制剂，对以poly(dI-dC)为底物的DNMT3B，DNMT3A和DNMT1的IC50值分别为7.5μM，8μM和12.5μM。IC50&TargetDNMT3BDNMT3ADNMT17.5μM(IC50)8μM(IC50)12.5μM(IC50)体外研究SGI-1027isaDNMTinhibitor,withIC50sof7.5μM,8μM,and12.5μMforDNMT3B,DNMT3A,andDNMT1withpoly(dI-dC)assubstrate.SGI-1027showsanIC50of6μMforDNMT1(hemimethylatedDNA).SGI-1027(1,2.5,or5µM)causesselectivedegradationofDNMT1inseveralhumancancercelllines,butshowslittleornocytotoxiceffectonrathepatomacells,anddoesnotinduceapoptosisinrathepatomacells[1].SGI-1027showsanEC50of0.9μMforhDNMT3A,andcausescytotoxicityonKG-1cells,withanEC50of4.4μM[2].PROTOCOLKinaseAssay[1]TodeterminethenatureofinhibitionofDNMTaseactivitybySGI-1027,DNMT1enzymeactivityismeasuredinpresenceofafixedconcentrationofSGI-1027(0,2.5,5,and10μM)whileoneofthetwo(Ado-MetorDNA)isvariedinaparticularreactionmixture.AtafixedconcentrationofDNA(500ng)varyingconcentrationsofAdo-Metusedarefrom25-500nM,respectively.Similarly,finalDNAconcentrationsarevariedfrom(25-500ng)at75nMAdo-Met[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]RathepatomaH4IIEcellsaregrowninDMEMsupplementedwithfetalbovineserum(10%)andcalfserum(10%).Cellsareseededinto96-wellplatesandafter48hexposedtoSGI-1027atconcentrationsrangingfrom0to300µM.ThesolubilityisdeterminedbyNephalometrytechniquesimmediatelyafterdosingandbeforeharvestingthecellsat24h.Followingtheexposureperiod,thecellsortheirsupernatant(culturemedium)areanalyzedforchangesincellproliferation(propidiumiodide),membraneleakage(α-GST),mitochondrialfunction[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromideandcellularATP],oxidativestress(intracellularGSHand8-isoprostane),andapoptosis(caspase-3).Thehalf-maximaltoxicconcentration(TC50)isdeterminedfromthedose-responsecurves[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•ProcNatlAcadSciUSA.2019Feb19;116(8):2961-2966.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•AgingCell.2021Dec7;e13526.•PharmacolRes.2022Jun;180:106244.•CommunBiol.2021Mar25;4(1):399.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DattaJ,etal.Anewclassofquinoline-basedDNAhypomethylatingagentsreactivatestumorsuppressorgenesbyblockingDNAmethyltransferase1activityandinducingitsdegradation.CancerRes.2009May15;69(10):4277-85.[2].RilovaE,etal.Design,synthesisandbiologicalevaluationof4-amino-N-(4-aminophenyl)benzamideanaloguesofquinoline-basedSGI-1027asinhibitorsofDNAmethylation.ChemMedChem.2014Mar;9(3):590-601.Mc