Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESDMACat.No.:HY-101410CASNo.:30344-00-4Synonyms:Symmetricdimethylarginine;NG,NG'-Dimethyl-L-arginine分?式:C?H??N?O?分?量:202.25作?靶點(diǎn):EndogenousMetabolite作?通路:MetabolicEnzyme/Protease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:67.5mg/mL(333.75mM;Needultrasonic)H2O:50mg/mL(247.22mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM4.9444mL24.7219mL49.4438mL5mM0.9889mL4.9444mL9.8888mL10mM0.4944mL2.4722mL4.9444mL請(qǐng)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(qǐng)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(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)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(qǐng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(12.36mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(12.36mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:2.5mg/mL(12.36mM);Suspendedsolution;Needultrasonic4.請(qǐng)依序添加每種溶劑：PBSSolubility:120mg/mL(593.33mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性SDMA(Symmetricdimethylarginine)?氧化氮(NO)合酶活性的內(nèi)性抑制劑。IC50&TargetHumanEndogenousMetabolite體外研究SDMAisthestructuralisomerofthecardiovascularriskmarkerasymmetricdimethylarginine,asanendogenousmarkerofrenalfunction.SDMAdoesnotdirectlyinhibitNOSbutisacompetitorofargininetransport.SDMAisprimarilyeliminatedbyrenalexcretionandisapromisingendogenousmarkerofglomerularfiltrationrate[1].SDMAinhibitsdosedependentlytheNOsynthesisinintactendothelialcells,whereasithasnoeffectonproteinexpressionofNOS[1].SDMAisinvolvedintheinflammatoryprocessofchronickidneydisease,activatingNF-κBandresultinginenhancedexpressionofIL-6andTNF-α[2].體內(nèi)研究SDMAishighlystableinserumandplasma,andtheassaydemonstratesexcellentanalyticalperformance.Inunaffecteddogs,SDMAremainsunchangedwhereasinaffecteddogs,SDMAincreasesduringdiseaseprogression,correlatingstronglywithanincreaseinsCranddecreaseinGFR[3].ChronicSDMAinfusionleadstoasignificantincreaseofSDMAlevelsinmice,buttheGFRdidnotchangeat4weeks.Nohistologicalchangesareobserved,particularlynoeffectonfibrosisorendotheliasnitricoxidesynthaseexpression.ThereisneitheraneffectofSDMAonsystolicbloodpressurenoronejectionfraction[4].PROTOCOLCellAssay[2]SDMAstocksolutionispreparedin0.9%NaClanddilutedinthecellculturemediumorinheparinizedwholebloodresultinginamaximaluremicconcentrationof6.1μMSDMA.Wholebloodisincubatedwithsaline(control)ordifferentdosesofADMA(0.6,3.6,and36μM)orSDMA(1.5,3.1,and6.1μM)for2hoursinahumidifiedatmosphereof5%CO2inairat37°C.CellsarefinallystainedforintracellularTNF-αorIL-6.Samplesareanalyzedwithaflowcytometer[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Eight-week-oldmaleC57Bl/6micereceivesvehicle-controlledinfusionofSDMA(250μmol/kg/days)forAdministration[4]28daysusingosmoticminipumps(n=24/group).Glomerularfiltrationrate,cardiacfunctionandbloodpressurearemonitored.BloodsamplesforSDMAdeterminationareobtainedatbaseline,2and4weeks.Miceareeuthanizedat4weekstoobtaintissueforrenalhistology[4].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].Bode-B?gerSM,etal.Symmetricaldimethylarginine:anewcombinedparameterforrenalfunctionandextentofcoronaryarterydisease.[2].SchepersE,etal.Symmetricdimethylarginineasaproinflammatoryagentinchronickidneydisease.ClinJAmSocNephrol.2011Oct;6(10):2374-83.[3].NabityMB,etal.SymmetricDimethylarginineAssayValidation,Stability,andEvaluationasaMarkerfortheEarlyDetectionofChronicKidneyDiseaseinDogs.JVetInternMed.2015Jul-Aug;29(4):1036-44.[4].VeldinkH,etal.EffectsofchronicSDMAinfusiononglomerularfiltrationrate,bloodpressure,myocardialfunctionandrenalhistologyinC57BL6/Jmice.NephrolDialTransplant.20