Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEINCB38579Cat.No.:HY-101188CASNo.:1246207-65-7分?式:C??H??N?O分?量:434.58作?靶點(diǎn):HistamineReceptor作?通路:GPCR/GProtein;Immunology/Inflammation;NeuronalSignaling儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.溶解性數(shù)據(jù)體外實驗DMSO:230mg/mL(529.25mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3011mL11.5054mL23.0107mL5mM0.4602mL2.3011mL4.6021mL10mM0.2301mL1.1505mL2.3011mLBIOLOGICALACTIVITY?物活性INCB38579?種具有?服活性、?度腦穿透和選擇性的組胺H4受體(HH4R)拮抗劑(hH4RIC50=4.8nM,mH4RIC50=42nM,rH4RIC50=32nM)。INCB38579具有抗炎和抗瘙癢的活性。IC50&TargetHumanH4ReceptorMouseH4ReceptorRatH4receptor4.8nM(IC50)42nM(IC50)21nM(IC50)體外研究INCB38579(0.1nM-10μM;1.5h)inhibitshistaminebindingtotherecombinanthumanandrodenthistamineH4receptors[1].INCB38579(0.1nM-10μM;20min)blockshistamine-inducedmigrationofdendriticcellsdifferentiatedfromhumanmonocytesandmousebonemarrowcells[1].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemENCB38579(0-30nM;1.5h)inhibitshistamine-inducedcellshapechangeandmigrationofpurifiedhumaneosinophilsdose-dependently[1].CellViabilityAssay[1]CellLine:HEK293cellsConcentration:0.1nM-10μMIncubationTime:1.5hoursResult:ShowedtheIC50valuesof4.8,42and21nMforthehuman,mouseandrathistamineH4receptors,respectively.CellViabilityAssay[1]CellLine:Humanmonocytes,mousebonemarrowcells,andhumaneosinophilsConcentration:0.1nM-10μMIncubationTime:20minResult:ShowedIC50sof13.2and77nMforhumanmonocytesandmousebonemarrowcells，respectively.ShowedIC50valuesofapproximately20-30nMforpurifiedhumaneosinophils.CellViabilityAssay[1]CellLine:HEK293cellsConcentration:0-30nMIncubationTime:1.5hoursResult:ShowedtheIC50valuesof4.8,42and21nMforthehuman,mouseandrathistamineH4receptors,respectively.體內(nèi)研究INCB38579(oralgavage;100mg/kg;once)inhibitshistamine-mediatedpruritusinmice[1].INCB38579(oralgavage;100mg/kg;once)showsantinociceptivefunctionsinthisacutemodelofinflammatorypain[1].INCB38579(oralgavage;3,10,30,and100mg/kg;once)inhibitsformalin-inducedpaininratsandmice[1].AnimalModel:FemaleCD-1micehistamine-inducedpruritus[1]Dosage:100mg/kgAdministration:Oralgavage;100mg/kg;onceResult:Reducedthenumberofscratchingboutssignificantly(P<0.05).2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:Sprague-Dawleyratsinjectedwithcarrageenan[1]Dosage:100mg/kgAdministration:Oralgavage;100mg/kg;onceResult:Increasedthepawwithdrawalthresholdfromabaselineof61gtoapproximately100g,achievingapproximately60%inmaximalpossibleeffect.AnimalModel:MaleSprague–DawleyratsandmaleICRmiceinjectedwithformalinintothehindpaws[1]Dosage:3,10,30,and100mg/kgAdministration:Oralgavage;3,10,30,and100mg/kg;onceResult:Showedasignificantdose-dependentanalgesiceffectfrom10to100mg/kginthephase1responseand30to100mg/kginthephase2responseinthemouseformalintest.Observedadose-dependentandstatisticallysignificanteffectinthephase1response,rangingfrom10to100mg/kg,intheratformalintest.REFERENCES[1].NiuShin,etal.INCB38579,anovelandpotenthistamineH?receptorsmallmoleculeantagonistwithanti-inflammatorypainandanti-pruriticfunctions.EurJPharmacol.2012Jan30;675(1-3):47-56.McePdfHeightCaution:Productha