D6808-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemED6808Cat.No.:HY-151905分⼦式:C₃₀H₂₅F₃N₆O₂分⼦量:558.55作⽤靶点:c-Met/HGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⾼度选择性、强效的c‑Met抑制剂，IC50值为2.9nM。D6808诱导细胞凋亡以及细胞周期阻滞。⽣物活性D6808D6808可⽤于⾮⼩细胞肺癌和胃癌的研究。IC50&TargetIC50:2.9nM(c‑Met)[1]体外研究D6808showsc-MetbiochemicalkinaseinhibitoryactivitywithanIC50valueof2.9nM[1].D6808(0.0001-10μM;5d)showscellularantiproliferativepotencytoHs746TcancercellswithanIC50valueof0.7nM[1].D6808displaysextraordinarykinomeselectivitywithIC50valuesof401.3,437.2,1386and203.9nMforAxl,TrkA,TrkBandTrkCkinase,respectively[1].D6808(0-10μM;72h)showantiproliferativepotencytoTpr-Metfusionprotein-transformedBa/F3cellswithIC50valuesof4.3,4.2,3.2,1.0,39.0and33.4nMforBa/F3-Tpr-Met,Ba/F3-Tpr-MetF1200L,Ba/F3-Tpr-MetM1250T,Ba/F3-Tpr-MetH1094Y,Ba/F3-Tpr-MetF1200I,Ba/F3-Tpr-MetL1195V,respectively[1].D6808(0-30nM;12h)affectsactivationofMETanddose-dependentlydecreasestheproteinlevelsofCDK2,CDK4,CDK6,cyclinD2,andcyclinE1andthecleaveactivationofPARPandcaspase-9inBa/F3-Tpr-Metcells[1].D6808(40nM;24h)inducescellapoptosisand87.37%G0/G1phasearrestinBa/F3-Tpr-Metcells[1].CellProliferationAssay[1]CellLine:Hs746TcancercelllineConcentration:0.0001-10μMIncubationTime:5daysResult:InhibitedthecellproliferationofHs746Tcancercells.1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEWesternBlotAnalysis[1]CellLine:Hs746TandBa/F3-Tpr-MetcelllinesConcentration:0,0.37,1.1,3.3,10and30nMIncubationTime:12hoursResult:SuppressedtheactivationofMETinHs746TandBa/F3-Tpr-Metcells.ApoptosisAnalysis[1]CellLine:Ba/F3-Tpr-MetcelllineConcentration:40nMIncubationTime:24hoursResult:Induced50.89%apoptosisafter48htreatment.体内研究1.19PharmacokineticPropertiesofD6808inRats[1].RatsIV2.0mg/kgRatsPO10.0mg/kgRatsIP10.0mg/kgT1/2(h)0.572.494.63Tmax(h)0.080.250.25Cmax(ng/mL)1071.2360.98282.12AUC0-t(h×ng/mL)483.8448.89820.38Vz(mL/kg)3470.78CL(mL/h/kg)4207.06MRT0-t(h)0.361.713.40F(%)2.0233.91REFERENCES[1].WangC,etal.DiscoveryofD6808,aHighlySelectiveandPotentMacrocyclicc-MetInhibitorforGastricCancerHarboringMETGeneAlterationTreatment.JMedChem.2022Nov24;65(22):15140-15164.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Fo