Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETLR7agonist2Cat.No.:HY-103039CASNo.:1642857-69-9分?式:C??H??N?O?分?量:336.35作?靶點:Toll-likeReceptor(TLR)作?通路:Immunology/Inflammation儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:160mg/mL(475.69mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.9731mL14.8655mL29.7309mL5mM0.5946mL2.9731mL5.9462mL10mM0.2973mL1.4865mL2.9731mL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備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。BIOLOGICALACTIVITY?物活性TLR7agonist2?種有效且有選擇性的Toll樣受體7(TLR7)激動劑，LEC值為0.4μM。IC50&TargetLEC:0.4μM(TLR7)[1]體外研究TLR7agonist2isapotentandselectiveToll-likeReceptor7(TLR7)agonistwithalowesteffective1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEconcentration(LEC)of0.4μMinHEK293cell.TLR7agonist2isfoundtobeselectiveforTLR7overTLR8withLECof>100μMforhumanTLR8.TLR7agonist2demonstrateslowinhibitionacrossfiveCYP450isozymes(IC50>10μM)andisalsonotatimedependentinhibitorofCYP4503A4.TLR7agonist2haslimitedinhibitionofthehERGpotassiumionchannel3H-dofetilidebindinginvitro(IC50>50μM)[1].體內(nèi)研究TLR7agonist2isfoundtoberapidlyclearedinconjunctionwithourtargetprofile.BothCmaxandAUCincreaselessthandoseproportionallybetween0.3and3mg/kgandmorethandose-proportionallybetween3and10mg/kg.TLR7agonist2caninduceanantiviralinterferonstimulatedgene(ISG)responsewithoutinducinganIFNαresponseatalowdose.TLR7agonist2alsoinducesa2.7logdecreaseinserumHBVviralloadfrom0.3mg/kg,andamaximum3.1logdecreaseisobservedfordosesbetween1and5mg/kg[1].PROTOCOLCellAssay[1]TheabilityofTLR7agonist2toactivatehumanTLR7and/orTLR8isassessedbyusingHEK293cells.Briefly,HEK293cellsaregrowninculturemedium(DMEMsupplementedwith10%FCSand2mMGlutamine).TransfectedcellsarethendetachedwithTrypsin-EDTA,washedinPBSandresuspendedinmediumtoadensityof1.67×105cells/mL.Thirtymicrolitersofcellsarethendispensedintoeachwellin384-wellplates,where10μLofTLR7-agonist-1in4%DMSOisalreadypresent.Following6hoursincubationat37°C,5%CO2,theluciferaseactivityisdeterminedbyadding15μLofSteadyLitePlussubstratetoeachwellandreadoutperformedonamicroplateimager.Lowesteffectiveconcentrations(LEC)valuesaredeterminedforTLR7-agonist-1[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAmouseinvivomodelisusedtodemonstratetheinitialproofofconcepttoinduceendogenousIFNα.SingleAdministration[1]oraladministrationof0.3,1,3,and10mg/kgdosesofTLR7agonist2isgiventohealthy,female,fastedC57Bl/6mice.ConcentrationsofTLR7agonist2andmouse-IFNviaELISAaremeasuredfromtheplasmaandcomparetovehicle[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].McGowanDC,etal.IdentificationandOptimizationofPyrrolo[3,2-d]pyrimidineToll-likeReceptor7(TLR7)SelectiveAgonistsfortheTreatmentofHepatitisB.JMedChem.2017Jul27;60(14):6137-6151.McePdfHeightCaution:Producthasnotbeen