c-Met-IN-22-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEc-Met-IN-22Cat.No.:HY-157387分⼦式:C₂₁H₁₀Cl₃F₂N₃O₂S分⼦量:512.74作⽤靶点:c-Met/HGFR;Apoptosis作⽤通路:ProteinTyrosineKinase/RTK;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性c-Met-IN-22（compound51am）⼀种⼝服有效的c-Met抑制剂，IC50值2.54nM。c-Met-IN-22具有抗增殖活性和抗肿瘤活性。c-Met-IN-22可以诱导细胞凋亡（apoptosis）[1]。IC50&Targetc-Metwildtypec-MetH1094Rc-MetD1228Hc-MetY1230H2.54nM(IC50)93.6nM(IC50)29.4nM(IC50)45.8nM(IC50)c-MetY1235Dc-MetM1250Tc-Metkitc-MetRon54.2nM(IC50)26.5nM(IC50)4.94nM(IC50)3.83nM(IC50)c-MetPDGFRαc-MetPDGFRβc-MetVEGFR-2c-MetFit-3425nM(IC50)513nM(IC50)527nM(IC50)6.12nM(IC50)c-MetFit-4276nM(IC50)体外研究c-Met-IN-22showsantiproliferativeactivityagainstMKN-45,A-549,HT-29,MDA-MB-231,HUVECandFHCwithIC50sof0.092,0.83,0.68,3.94,2.54and8.63μM,respectively[1].c-Met-IN-22showsanti-drugresistenceagainsttH1094R,D1228H,Y1230H,Y1235D,andM1250T,withIC50valuesof93.6,29.4,45.8,54.2and26.5nM,respectively[1].c-Met-IN-22(0,2.5,5.0,and10.0ꢀμM,24h)inhibitsc-MetphosphorylationinMKN-45inadose-dependentmanner[1].c-Met-IN-22(0.4,0.8,and1.2ꢀμM,24ꢀh)inducescellcyclearrestatG2phaseandapotosisofMNK-45inadose-dependentmanner[1].ApoptosisAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:MNK-45cellsConcentration:0.4,0.8,1.2μMIncubationTime:24hResult:Inducedcellapoptosisinadose-dependentmanner.CellCycleAnalysis[1]CellLine:MNK-45cellsConcentration:0.4,0.8,1.2μMIncubationTime:24hResult:InducedcellcyclearrestatG2phaseinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:MNK-45cellsConcentration:0,2.5,5,10μMIncubationTime:24hResult:Inhibitedc-Metphosphorylationinadose-dependentmanner.体内研究c-Met-IN-22(10mg/kg;p.o.;singledose)exhibitsgoodoralbioavailability(F=69%)inBALB/cmice,witheliminationhalf-timeof5.6handclearanceof0.87L/h•kg[1].c-Met-IN-22(1.5mg/kg;i.v.)exhibitsaneliminationhalf-timeof3.2h[1].PharmacokineticAnalysisofc-Met-IN-22inBALB/cmice[1]RouteDose(mg/kg)AUC0→∞(μg·h/mL)T1/2(h)Tmax(h)Cmax(ng/mL)Cl(L/h·kg)F(%)i.v.1.5mg/kg2.53.2/5520.6/p.o.10mg/kg1756/69AnimalModel:PharmacokineticAnalysisinBALB/cmiceDosage:p.o.10mg/kg;i.v.1.5mg/kgAdministration:Intravenous(i.v.)injection,Oraladministration(p.o.)Result:Characterisedgoodmaximumconcentration,plasmaexposureandeliminationhalf-timeinpharmacokinetics.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].XiangNan,etal.Design,synthesis,andbiologicalevaluationofthiazole/thiadiazolecarboxamidescaffold-basedderivativesaspotentialc-Metkinaseinhibitorsforcancertreatment.JEnzymeInhibMedChem.2023Dec;38McePdfHeightCaution:Producthasnotbeenfullyvalidatedforme