Capmatinib-dihydrochloride-hydrate-INC280-dihydrochloride-hydrate-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECapmatinibdihydrochloridehydrateCat.No.:HY-13404CCASNo.:1865733-40-9Synonyms:INC280dihydrochloridehydrate;INCB-28060dihydrochloridehydrate分?式:C??H??Cl?FN?O?分?量:503.36作?靶點:c-Met/HGFR;Apoptosis作?通路:ProteinTyrosineKinase/RTK;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Capmatinib(INC280;INCB28060)dihydrochloridehydrate?種有效的、?服活性的、選擇性的、ATP競爭性的c-Met激酶抑制劑(IC50=0.13nM)。Capmatinibdihydrochloridehydrate可抑制c-MET的磷酸化，以及c-MET通路下游效應蛋?如ERK1/2、AKT、FAK、GAB1和STAT3/5。Capmatinibdihydrochloridehydrate有效抑制c-Met依賴性腫瘤細胞的增殖和遷移，并有效誘導細胞凋亡。在腫瘤??模型中表現(xiàn)出抗腫瘤活性。Capmatinibdihydrochloridehydrate主由CYP3A4和醛氧化酶代謝。IC50&Targetc-Met0.13nM(IC50)體外研究Capmatinib(INCB28060)inhibitsc-METphosphorylationwithanIC50valueofapproximately1nMandaconcentrationofapproximately4nMinhibitsc-METmorethan90%,whichisreversibleandtheeffectissignificantlyreducedinseveralhoursafterthecompoundisremovedandcompletelydisappearedby48hours[1].Capmatinib(INCB28060)(0-10000nM;72h)inhibitstheproliferationofSNU-5,S114,H441andU-87MG[1].Capmatinib(INCB28060)(0.06-62.25nM;2h)effectivelyinhibitsphosphorylationofc-METaswellasc-METpathwaydownstreameffectorssuchasERK1/2,AKT,FAK,GAB1,andSTAT3/5[1].Capmatinib(INCB28060)(0.24-63nM;overnight)preventsHGF-stimulatedH441cellmigration[1].Capmatinib(INCB28060)(0.5-50nM;20min)suppressesphosphorylationofbothEGFRandHER-3rapidly[1].Capmatinib(INCB28060)(0-333nM;24h)inducesapoptosisinSNU-5cells[1].1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellViabilityAssay[1]CellLine:SNU-5,S114,H441andU-87MGConcentration:0-10000nMIncubationTime:72hResult:InhibitedthecellviabilityofSNU-5andS114,aswellasthecolonyformationofH441andU-87MG,withIC50valuesof1.2nM,12.4nM,~0.5nMand2nM,respectively.CellMigrationAssay[1]CellLine:H441(stimulatedwith50ng/mLrecombinanthumanHGFfor24h)Concentration:0.24,1,4,16and63nMIncubationTime:OvernightResult:PreventedHGF-stimulatedH441cellmigration,withIC50ofapproximately2nM,andlesscellmigrationat16nM.WesternBlotAnalysis[1]CellLine:SNU-5Concentration:0.06,0.24,0.98,3.91,15.63and62.25nMIncubationTime:2hResult:Effectivelyinhibitedphosphorylationofc-METaswellasc-METpathwaydownstreameffectorssuchasERK1/2,AKT,FAK,GAB1,andSTAT3/5.WesternBlotAnalysis[1]CellLine:H1993cellsConcentration:0.5,5and50nMIncubationTime:20minResult:SuppressedphosphorylationofbothEGFRandHER-3rapidlyandaseffectivelyasthecompoundinhibitedc-METphosphorylationinH1993cells.ApoptosisAnalysis[1]CellLine:SNU-5cellsConcentration:0.017,0.15,1.37,12.33,111and333nM2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:24hResult:EffectivelyinducedDNAfragmentation.體內(nèi)研究Capmatinib(INCB28060)(1-30mg/kg;PO,twicedaily,for2weeks)exhibitsdose-dependentinhibitionoftumorgrowth,andshowswelltoleranceatalldosesduringthetreatmentperiods,withnoevidenceofoverttoxicityorweightlossinU-87MGtumormicemodel[1].Capmatinib(INCB28060)(0.03-10mg/kg;PO,singledosage)causesinhibitionofc-METphosphorylationinS114tumormicemodel[1].AnimalModel:FemaleBalb/cnu/numice(inoculatedsubcutaneouslywith5×106U-87MGglioblastomacells)[1]Dosage:1,3,10and30mg/kgAdministration:PO,twicedaily,for2weeksResult:Exhibiteddose-dependentinhibitionoftumorgrowthwith35%and76%at1and3mg/kgoncedaily;resultedinpartialregressionsin6of10U-87MGtumor-bearingmiceat10mg/kgoncedaily;andshowedwelltoleranceatalldosesduringthetreatmentperiods,withnoevidenceofoverttoxicityorweightloss.AnimalModel:FemaleBalb/cnu/numice(inoculatedsubcutaneouslywith4×106S114tumorcells)[1]Dosage:0.03,0.1,0.3,1,3and10mg/kgAdministration:PO,singledosageResult:Causedapproximately50%and90%inhibitionofc-METphosphorylationat0.03and0.3mg/kgafteradministrationof30min,andinhibitionofphospho-c-METexceeded90%after7hours.戶使?本產(chǎn)品發(fā)表的科研?獻?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?JExpClinCancerRes.2022Sep16;41(1):275.?CancerResTreat.2020Jul;52(3):973-986.?BiochemBiophysRep.2020Jan17;21:100726.?DepartmentCancerBiology.WayneStateUniversity.2014Jan.Seemorecustomervalidationsonwww.MedChemEREFERENCES3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].LiuX,etal.Anovelkinaseinhibitor,INCB28060,blocksc-MET-dependentsignaling,neoplasticactivities,andcross-talkwithEGFRandHER-3.ClinCancerRes.2011Nov15;17(22):7127-38.[2].BaltschukatS,etal.Capmatinib(INC280)IsActiveAgainstModelsofNon-SmallCellLungCancerandOtherCancerTypeswithDefinedMechanismsofMETActivation.ClinCancerRes.2019May15;25(10):3164-3175.[3].DhillonS.Capmatinib: