RO9021-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERO9021Cat.No.:HY-16902CASNo.:1446790-62-0分⼦式:C₁₈H₂₅N₇O分⼦量:355.44作⽤靶点:Syk作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:3.03mg/mL(8.52mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8134mL14.0671mL28.1341mL5mM0.5627mL2.8134mL5.6268mL10mM---------请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。BIOLOGICALACTIVITY⽣物活性RO9021⼀种可⼝服的，ATP竞争性的SYK抑制剂，IC50值为5.6nM。IC50&TargetIC50:5.6nM(SYK)体外研究RO9021isahighlyselectiveSYKinhibitorwithlowS-scoresof0.003forS(99)and0.015forS(90),1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师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