SR9009-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemESR9009Cat.No.:HY-16989CASNo.:1379686-30-2分?式:C??H??ClN?O?S分?量:437.94作?靶點(diǎn):Autophagy作?通路:Autophagy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:≥100mg/mL(228.34mM)掃描?維碼，H2O:<0.1mg/mL(insoluble)運(yùn)?溶解?案計(jì)算器*"≥"meanssoluble,butsaturationunknown.獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.2834mL11.4171mL22.8342mL5mM0.4567mL2.2834mL4.5668mL10mM0.2283mL1.1417mL2.2834mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。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.請(qǐng)依序添加每種溶劑：1%DMSO99%saline2.Solubility:0.5mg/mL(1.14mM);Suspendedsolution;Needultrasonic請(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:2.08mg/mL(4.75mM);Suspendedsolution;Needultrasonic此?案可獲得2.08mg/mL(4.75mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。1/3www.MedChemEwww.MedChemE以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述3.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.75mM);Suspendedsolution;Needultrasonic此?案可獲得2.08mg/mL(4.75mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶4.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.08mg/mL(4.75mM);Clearsolution此?案可獲得≥2.08mg/mL(4.75mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。5.以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。請(qǐng)依序添加每種溶劑：5%DMSO40%PEG3005%Tween-8050%saline6.Solubility:2.5mg/mL(5.71mM);Suspendedsolution;Needultrasonic請(qǐng)依序添加每種溶劑：5%DMSO95%(20%SBE-β-CDinsaline)7.Solubility:2.5mg/mL(5.71mM);Suspendedsolution;Needultrasonic請(qǐng)依序添加每種溶劑：6%DMSO10%CremophorEL84%ddH2OSolubility:20mg/mL(45.67mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性SR9009REV-ERBα/β激動(dòng)劑，作?REV-ERBα和REV-ERBβ的IC50分別為670nM和800nM。IC50&TargetIC50:670nM(Rev-ErbBα),800nM(Rev-ErbBβ)[1]體外研究SR9009dose-dependentlyincreasestheREV-ERB-dependentrepressoractivityassessedinHEK293cellsexpressingachimericGal4DNABindingDomain(DBD)-REV-ERBligandbindingdomain(LBD)αorβandaGal4-responsiveluciferasereporter(SR9009:REV-ERBαIC50=670nM,REV-ERBβIC50=800nM).SR9009potentlyandefficaciouslysuppressestranscriptioninacotransfectionassayusingfull-lengthREV-ERBαalongwithaluciferasereporterdrivenbytheBmal1promoter(IC50=710nM).SR9009suppressestheexpressionofBMAL1mRNAinHepG2cellsinaREV-ERBα/β-dependentmanner.DirectbindingoftheSR9009toREV-ERBαisalsoconfirmedusingcirculardichrosimanalysis(Kd=800nM)[1].體內(nèi)研究Whilethestressofhandlingandtwice-dailyinjectionscausedweightlossinvehicle-treatedcontrols,weightlossofSR9009-treatedanimalsis60%greater.SR9009(100mg/kg,i.p.)treatedmiceexhibitamoreseverereductioninadiposity.Plasmanon-esterifiedfattyacids(NEFA)arealsoreduced(23%)alongwithplasmaglucose(19%)intheSR9009treatedanimals.Inthewhiteadiposetissue(WAT),SR9009treatmentresultsinadecreaseinexpressionofgenesencodingenzymesinvolvedintriglyceride(TG)synthesisasisalsoobservedinleanmice[1].PROTOCOLCellAssay[1]HEK293cellsaregrownin96-wellplates(1×106/well)andaretransientlytransfectedusingLipofectamine.Cellsaretransfectedwithatotalof200ngofDNAperwellconsistingofthepGL4mIL-17fireflyluciferase2/3www.MedChemEwww.MedChemEreporterconstruct,thepGL4mIL-17+CNS-5fireflyluciferasereporterconstruct,orthepGL4mIL-172kBROREmutant(100ng/well),anactinpromoterRenillareniformisluciferasereporter(50ng/well),andeithercontrolvectoraloneorthetestDNA(full-lengthRORαorfull-lengthRORγat50ng/well).All48humannuclearreceptorsarerepresentedinthespecificityassayandSR9009istestedataconcentrationof20μM.TheformatoftheassayisacotransfectionassaywithGal4DNAbindingdomain-nuclearreceptorfusionsinHEK293cells[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]ForcircadiangeneexpressionexperimentsmaleC57BL6mice(8-10weeksofage)areeithermaintainedonaL:D(12h:12h)cycleoronconstantdarkness.Atcircadiantime(CT)0animalsareadministeredasingledoseof100mg/kgSR9009orSR9011(i.p.)andgroupsofanimals(n=6)aresacrificedatCT0,CT6,CT12andCT18.GeneexpressionisdeterminedbyrealtimeQPCR.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2018Oct12;9(1):4246.?JNeuroinflammation.2020Jan31;17(1):43.?Chemosphere.2021Jan;263:128020.?CellProlif.2021Jan13;e12988.?BiochemPharmacol.2020Feb;172:113773.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SoltLA,etal.RegulationofcircadianbehaviourandmetabolismbysyntheticREV-ERBagonists.Nature.2012Mar29;485(7396):62-68.McePdfHeigh