SGC2085-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESGC2085Cat.No.:HY-100565CASNo.:1821908-48-8分?式:C??H??N?O?分?量:312.41作?靶點(diǎn):HistoneMethyltransferase作?通路:Epigenetics儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥32mg/mL(102.43mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2009mL16.0046mL32.0092mL5mM0.6402mL3.2009mL6.4018mL10mM0.3201mL1.6005mL3.2009mL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(chǔ)備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(8.00mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.00mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.00mM);ClearsolutionBIOLOGICALACTIVITY?物活性SGC2085?種具有?效性和選擇性的CARM1抑制劑,IC50值為50nM。IC50&TargetIC50:50nM(CARM1)[1]體外研究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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?ActaPharmacolSin.2021Apr13.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].FerreiradeFreitasR,etal.DiscoveryofaPotentandSelectiveCoactivatorAssociatedArginineMethyltransferase1(CARM1)InhibitorbyVirtualScreening.JMedChem.2016Jul28;59(14):6838-47.McePdfHeightC