BMS-582949-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEBMS-582949Cat.No.:HY-14305CASNo.:623152-17-0分子式:C₂₂H₂₆N₆O₂分子量:406.48作用靶点:p38MAPK作用通路:MAPK/ERKPathway储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性BMS-582949(compound7k)是一种口服有效的、高度选择性的p38αMAP酶抑制剂，对p38α的IC50为13nM，对TNFα的IC50为50nM。BMS-582949可用于研究类风湿性关节炎。IC50&Targetp38α13nM(IC50)体内研究BMS-582949(5mg/kg,p.o.,90min)reducestheLPSinducedTNFαproductionsignificantlyinmurinemodelsofacuteinflammationfromBALB/cfemalemice[1].BMS-582949(0.3-100mg/kg,p.o.,q.d/b.i.d)reducespawswellingsignificantly[1].BMS-582949intravenousinjection(i.v.)dissolutionprotocoluses25%NMP,33%PEG400,9%PG,and33%waterasavehicle[1].BMS-582949oralgavage(p.o.)dissolutionprotocolusesPEG400asavehicle[1].PharmacokineticPropertiesofCompound7kinMiceandRats[1]Compound7k在小鼠和大鼠中的药代动力学分析[1]mouserat%Fpo9060Cmax(μM)15.37.0Tmax(h)1.01.5T1/2(h)2.64.0MRT(h)3.33.4CL(mL/min/kg)4.45.4Vss(L/kg)0.91.1AUC0-8h(μM•h)75.5AUC0-24h(μM•h)45.4InVitroProfileof7k[1]体外代谢分析[1]profilingassaysresultslivermicrosomemetabolicrate(nmol/min/mg)mouse:0.0111/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemErat:0.008human:0.013hepatocytemetabolicrate(nmol/min/millioncells)mouse:0.006rat:0.015human:0.015P450IC50(μM)>40for1A2,2C92C19,and2D618-40for3A4Caco-2permeability(nm/s)121-134serumproteinbinding(%)mouse:86.3rat:89.7human:81.5AmesnegativeinT98andT100±S9activationSOSchromotestnegativeHHAIC50(μM)>138hERGinhibition16%at30μMkinaseselectivity>2000foldover57diversekinase450foldoverJnk2190foldoverRaf5foldoverp38αAnimalModel:murinemodelsofacuteinflammationfromBALB/cfemalemice[1]Dosage:5mg/kgAdministration:Oralgavage(p.o.),detectioncontentat90minafterLPSinjectionResult:ReducedtheTNFαproductionby89%at2h,by78%at6hbeforetheLPSchallenge.AnimalModel:Ratadjuvantarthritis(ratAA)modelsfromMaleLewisrats[1]Dosage:1,10,100mg/kg,oncedaily(q.d)Administration:Oralgavage(p.o.)Result:Reducedpawswellingwithdose-dependent,withefficacyobservedatdosesof10and100mg/kg.AnimalModel:Ratadjuvantarthritis(ratAA)modelsfromMaleLewisrats[1]Dosage:0-5mg/kg,b.i.dAdministration:Oralgavage(p.o.)Result:Improvedefficacymarkedlyofreductioninpawswellingatdosesof1and5mg/kg.Reducedpawswellingsignificantlyatdosesaslowas0.3mg/kg.客户使用本产品发表的科研文献• OncolRes.2021Feb11.2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCESLiuC,etal.Discoveryof4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide(BMS-582949),aclinicalp38αMAPkinaseinhibitorforthetreatmentofinflammatorydiseases.JMedChem.2010Sep23;53(18):6629-39.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor