RO9021-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERO9021Cat.No.:HY-16902CASNo.:1446790-62-0分?式:C??H??N?O分?量:355.44作?靶點:Syk作?通路:ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:3.03mg/mL(8.52mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8134mL14.0671mL28.1341mL5mM0.5627mL2.8134mL5.6268mL10mM---------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(fù)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RO9021?種可?服的，ATP競爭性的SYK抑制劑，IC50值為5.6nM。IC50&TargetIC50:5.6nM(SYK)體外研究RO9021isahighlyselectiveSYKinhibitorwithlowS-scoresof0.003forS(99)and0.015forS(90),1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEindicatingthatSYKistheonlykinasewith99%competitionwithRO9021inatotalof392testedkinases.RO9021inhibitsanti-IgMinducedphosphorylationofBTK,PLCγ2,AKTandERK,indicatingthatblockadeofSYKkinaseactivitybyRO9021resultsinattenuationofBCRdownstreamsignalingcascade.RO9021selectivelysuppressesB-cellreceptorsignaling.RO9021alsodisplaysasimilarinhibitorypotency(IC50=22.8±1.7nM)inaFcεR-mediatedmastcellactivationanddegranulationassay[1].PROTOCOLKinaseAssay[1]TheinhibitorypotencytoSYKisdeterminedinaradiometricassayusinginactiveSYKkinase.Briefly,SYKproteinisdephosphorylatedbyPTP1Bphosphataseandthenthereactionisinitiatedbytheadditionofsubstratecocktailthatcontained20μMATP,0.025μCiATP-γ-33Pand10μMbiotinylatedsyntheticpeptide.Thereactioniscarriedoutfor30minutesandresulting33Pincorporationisdeterminedbytopcounter.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalBriefly,DBA1/Jmalemiceareinjectedintradermallywith0.1mLbovinetypeIIcollagen(100μg)andAdministration[1]completeFreund’sadjuvantfollowedbysecondimmunizationonday21withbovinetypeIIcollagenandincompleteFreundadjuvant.RO9021isadministeredorally,randomizedintodifferentgroups(14mice/groups),everydayfor14daysstartingonthedayaftersecondimmunization.Clinicalarthritisscores(1to4)ofindividualpawsareassessedandthearthriticindexforeachmouseisdeterminedbyaddingtheindividualscoresofallfourpaws.ThelevelofcytokinesinserumisdeterminedbyLuminexanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].LiaoC,etal.Selectiveinhibitionofspleentyrosinekinase(SYK)withanovelorallybioavailablesmallmoleculeinhibitor,RO9021,impingesonvariousinnateandadaptiveimmuneresponses:implicationsforSYKinhibitorsinautoimmunediseasetherapy.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedi