Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPF-04217903phenolsulfonateCat.No.:HY-12017BCASNo.:1159490-85-3分?式:C??H??N?O?S分?量:546.56作?靶點:c-Met/HGFR作?通路:ProteinTyrosineKinase/RTK儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PF-04217903phenolsulfonate?種?效的ATP競爭性c-Met激酶抑制劑，Ki為4.8nM。PF-04217903phenolsulfonate相對于208個激酶顯?出1000倍以上的選擇性。具有抗?管?成特性。IC50&TargetKi:4.8nM(humanc-Met)[1]體外研究PF-04217903phenolsulfonate(0.1-10000nM;48-72hours)inhibitsproliferationofc-Met–amplifiedhumanGTL-16gastriccarcinomaandH1993NSCLCcellswithIC50valuesof12and30nM,respectively[1].PF-04217903phenolsulfonate(1.5-3333nM;48hours)inducesapoptosisofGTL-16cells(IC50=31nM)[1].PF-04217903phenolsulfonatealsoinhibitsHGF-mediatedcellmigrationandMatrigelinvasioninseveralc-Met–overexpressingtumorcelllinessuchashumanNCI-H441lungcarcinomaandHT29coloncarcinomawithIC50valuescomparablewiththoseforinhibitionofc-Metphosphorylationinthesecelllines(IC50=7-12.5nM)[1].PF-04217903phenolsulfonatedisplayssimilarpotencytoinhibittheactivityofc-Met-H1094R,c-Met-R988C,andc-Met-T1010IwithIC50of3.1nM,6.4nM,and6.7nM,respectively.PF-04217903phenolsulfonatehasnoinhibitoryactivityagainstc-Met-Y1230CwithIC50of>10μM[3].CellViabilityAssay[1]CellLine:GTL-16,H1993cellsConcentration:0.1,1,10,100,1000,10000nMIncubationTime:48-72hours1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Inhibitedproliferationofc-Met–amplifiedhumanGTL-16gastriccarcinomaandH1993NSCLCcellswithIC50valuesof12and30nM,respectively.ApoptosisAnalysis[1]CellLine:GTL-16cellsConcentration:1.5-3333nMIncubationTime:48hoursResult:InducedapoptosisofGTL-16cells.體內(nèi)研究PF-04217903phenolsulfonate(1-30mg/kg;p.o.;dailyfor16days)showsdose-dependenttumorgrowthinhibition,whichcorrelatedwiththeinhibitioninc-Metphosphorylationinthesetumors[1].PF-04217903phenolsulfonate(5-50mg/kg,p.o.;oncedailyfor3days)dosedependentlyinhibitsc-Met,Gab-1,Erk1/2,andAKTphosphorylationandinducedapoptosis(cleavedcaspase-3)inU87MGxenografttumorsatalldoselevels.PF-04217903phenolsulfonateshowsasignificantdose-dependentreductionofhumanIL-8levelsinboththeU87MGandGTL-16modelsanddecreaseshumanVEGFAlevelsintheGTL-16model.PF-04217903phenolsulfonatestronglyinducesphospho-PDGFRβlevelsinU87MGxenografttumors[1].AnimalModel:Femalenu/numice(GTL-16xenograftmodel)[1]Dosage:1,3,10,30mg/kgAdministration:Oral;dailyfor16daysResult:Showeddose-dependenttumorgrowthinhibition,andwascorrelatedwiththeinhibitioninc-Metphosphorylationinthesetumors.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].ZouHY,etal.SensitivityofselectedhumantumormodelstoPF-04217903,anovelselectivec-Metkinaseinhibitor.MolCancerTher.2012Apr;11(4):1036-47.[2].CuiJJ,etal.Discoveryofanovelclassofexquisitelyselectivemesenchymal-epithelialtransitionfactor(c-MET)proteinkinaseinhibitorsandidentificationoftheclinicalcandidate2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol(PF-2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE04217903)forthetreatmentofcancer.JMedChem.2012Sep27;55(18):8091-109.[3].TimofeevskiSL,etal.Enzymaticcharacterizationofc-Metreceptortyrosinekinaseoncogenicmutantsandkineticstudieswithaminopyridineandtriazolopyrazineinhibitors.Biochemistry.2009Jun16;48(23):5339-49.McePdfHeightCaution