SGC2085-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESGC2085Cat.No.:HY-100565CASNo.:1821908-48-8分⼦式:C₁₉H₂₄N₂O₂分⼦量:312.41作⽤靶点:HistoneMethyltransferase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:≥32mg/mL(102.43mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.2009mL16.0046mL32.0092mL5mM0.6402mL3.2009mL6.4018mL10mM0.3201mL1.6005mL3.2009mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(8.00mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.00mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.00mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性SGC2085⼀种具有⾼效性和选择性的CARM1抑制剂,IC50值为50nM。IC50&TargetIC50:50nM(CARM1)[1]体外研究SGC2085whichfeaturesamethylatpositionR1anda3,5-dimethylphenoxyatR2hasanIC50of50nMforCARM1andisover100-foldselectiveforCARM1overPRMT6.TheseresultsindicatethatthepresenceofasubstituentatR1isessentialforpotentandselectiveinhibitionofCARM1.WiththeexceptionofPRMT6(IC50=5.2μM),SGC2085doesnotinhibitotherPRMTs.Consideringitssmallsize(MW=312.4Da),SGC2085hasanexcellentselectivityprofile,whichcanprobablybefurtherimprovedbyexploitingdifferencesinthebindingsitesofthetwoenzymesoutsidetheargininebindingpocket.CompoundSGC2085alsoshowscompleteselectivityagainstapanelof21humanproteinmethyltrans-ferasestestedatthreedifferentconcentrations(1,10,and50μM).TocharacterizethemechanismofactionofSGC2085insolution,IC50valuesaredeterminedatvariousconcentrationsofSAMandpeptidesubstrate.IncreasingconcentrationofsubstratepeptideorcofactordoesnotaffectIC50values,indicativeofanoncompetitivemechanismofinhibition,whichhasbeenpreviouslyshownforotherproteinmethyltransferaseinhibitorsbindingatthesubstratepocket[1].NocellularactivityisobservedforSGC2085whentestedupto10μM(48hexposureinHEK293cells),whilemethylationofBAF155isabrogatedby10μMofthedualCARM1/PRMT6inhibitorMS049.WeassumethattheabsenceofcellularactivityforSGC2085isduetopoorpermeability[1].PROTOCOLCellAssay[1]SGC2085isdissolvedinDMSOanddilutedwithappropriatemediumbeforeuse.HEK293cellsaregrownin12-wellplatesinDMEMsupplementedwith10%FBS,penicillin(100U/mL),andstreptomycin(100μg/mL).ThirtypercentconfluentcellsaretreatedwithinhibitorsorDMSO.After48h,mediaareremovedandcellsarelysedin100μLoftotallysisbuffer(20mMTris-HClpH8.0,150mMNaCl,1mMEDTA,10mMMgCl2,0.5%TritonX-100,12.5U/mLbenzonase),completeEDTA-freeproteaseinhibitorcocktail.After3minincubationatroomtemperature,SDSisaddedto1%finalconcentration.LysatesarerunonSDS,andimmunoblottingisdoneasoutlinedbelowtodeterminethelevelsofunmethylatedandmethylatedBAF155[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•ActaPharmacolSin.2021Apr13.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].FerreiradeFreitasR,etal.DiscoveryofaPotentandSelectiveCoactivatorAssociatedArginineMethyltransferase1(CARM1)InhibitorbyVirtualScreening.JMedChem.2016Jul28;59(14):6838-47.McePdfHeightC