Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZunsemetinibCat.No.:HY-139553CASNo.:1640282-42-3Synonyms:ATI-450;CDD-450分?式:C??H??ClF?N?O?分?量:513.92作?靶點:MAPKAPK2(MK2)作?通路:MAPK/ERKPathway儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(194.58mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.9458mL9.7291mL19.4583mL5mM0.3892mL1.9458mL3.8917mL10mM0.1946mL0.9729mL1.9458mL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Zunsemetinib(CDD-450)?種具有?服活性的p38α絲裂原激活蛋?激酶激活蛋?激酶2(MK2)通路抑制劑。Zunsemetinib可?于免疫炎癥性疾病的研究[1]。IC50&TargetMK2[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體外研究Zunsemetinib(1and10μM;1hour;WTandNOMIDBMMs)hasnoeffectonNLRP3expression,butdecreasesIL-1βexpressionbypromotingIL-1βmRNAdegradation[1].Zunsemetinib(0.4nM~1μM;16hours;PBMC)reducesIL-1βsecretionandpromotesIL-1βmRNAinstability[1].Zunsemetinibselectivelyblocksp38αMAPKactivationoftheproinflammatorykinaseMK2whilesparingp38αactivationofothereffectorssuchasPRAKandATF2.ZunsemetinibinhibitsinvitroosteoclastformationinducedbyRANKL[1].RT-PCR[1]CellLine:WTandNOMIDBMMsConcentration:1and10μMIncubationTime:1hourResult:HadnoeffectonNLRP3expression,butdecreasedIL-1βexpressionbypromotingIL-1βmRNAdegradation.體內(nèi)研究Zunsemetinib(1,000ppm;p.o.)blocksLPS-inducedTNF-αexpressionpersistedforupto4weeksafterdosing[1].Zunsemetinib(10and20mg/kg;p.o.)increasesbonedensity[1].ZunsemetinibpreventsosteopeniainNOMIDcmicethroughinhibitionofosteoclastogenesis[1].AnimalModel:8-week-oldWTfemalemice[1]Dosage:1,000ppmAdministration:P.o.Result:BlockedLPS-inducedTNF-αexpressionpersistedforupto4weeksafterdosing.AnimalModel:Rats[1]Dosage:10and20mg/kgAdministration:P.o.Result:Increasedbonedensity.REFERENCES[1].Zunsemetinib(ATI-450)–InvestigationaloralMK2pathwayinhibitor[2].AclarisTherapeuticsAnnouncesATI-450(MK2pathwayInhibitor)publicationinJournalofExperimentalMedicine[3].WangC,etal.Selectiveinhibitionofthep38αMAPK-MK2axisinhibitsinflammatorycuesincludinginflammasomeprimingsignals.JExpMed.2018;215(5):1315-1325.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMcePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Fo