Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEUSP7-IN-18Cat.No.:HY-174301CASNo.:3052223-40-9分?式:C??H??ClN?O?S分?量:546.08作?靶點(diǎn):Deubiquitinase;DNAMethyltransferase;MDM-2/p53作?通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性USP7-IN-18(CompoundX21)(0.25-1μM,24h)作為新型USP7抑制劑，通過直接抑制酶活性和調(diào)控下游通路(包括?次報(bào)道的PCLAF靶點(diǎn))[1]。USP7-IN-18(0.01-100μM,72h)顯著抑制??病(RS4;11)和結(jié)腸癌(MC38/CT26.WT)細(xì)胞增殖[1]。USP7-IN-18(2.5μM,0.5h)對(duì)USP7表現(xiàn)出較?的選擇性，優(yōu)于其他8種去泛素化酶[1]。USP7-IN-18(1.95-2000nM,3min)經(jīng)過SPR分析發(fā)現(xiàn)與USP7的催化結(jié)構(gòu)域結(jié)合，KD值為4.9μM[1]。體外研究USP7-IN-18(CompoundX21)(1.95-2000nM,3min)bindstothecatalyticdomainofUSP7withaKDvalueof4.9μM,asdeterminedbySPRanalysis[1].USP7-IN-18(0.25-1μM,24h)actsasanovelUSP7inhibitorbydirectlyinhibitingenzymaticactivityandregulatingdownstreampathways,includingthefirst-reportedtargetPCLAF[1].USP7-IN-18(0.01-100μM,72h)significantlyinhibitsproliferationofleukemia(RS4;11)andcoloncancer(MC38/CT26.WT)cells[1].USP7-IN-18(2.5μM,0.5h)exhibitshighselectivityforUSP7overeightotherdeubiquitinases,includingUSP47(themosthomologoustoUSP7)[1].CellViabilityAssay[1]CellLine:RS4;11cells,MC38cells,CT26.WTcellsConcentration:0.01-100μMinRS4;11cells,0.5-100μMinMC38cellsandCT26.WTcellsIncubationTime:72hResult:DemonstratedantiproliferativeactivityagainstthehumanleukemiaRS4;11celllinewithanIC50valueof0.65μM.ExhibitedantiproliferativeactivityagainstMC38andCT26.WTmousecoloncancercell1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemElineswithIC50valuesof2.93μMand2.89μM,respectively.WesternBlotAnalysis[1]CellLine:RS4;11cellsConcentration:0.25μM,0.5μM,1μMIncubationTime:24hResult:DemonstrateddownregulationofDNMT1,UHRF1,MDM2,TRIM27,andPCLAF,withconcurrentupregulationofp53andp21.SignificantlyreducedPCLAFproteinlevels.SlightlyreducedUSP7proteinlevels.體內(nèi)研究USP7-IN-18(CompoundX21)(5mg/kg,10mg/kg,i.p.,dailyfor16days)showspotentantitumoractivityintheMC38tumor-bearingC57BL/6Jmice[1].AnimalModel:MC38tumor-bearingC57BL/6Jfemalemice(8weeks)[1].Dosage:5mg/kg,10mg/kgAdministration:Dailyintraperitonealinjection(i.p.),atthecorrespondingdosesfor16days.Result:Demonstratedsignificanttumorgrowthinhibition(TGI=58.2%)at10mg/kgonday16,whileshowingweakerefficacyat5mg/kg,indicatingdose-dependentantitumoractivity.Significantlyreducedtumormassinimmunocompetentmice,confirmingeffectivetumorgrowthsuppression.Causedtransientbodyweightlossduetoinitialstressresponse,withsubsequentrecoveryobservedinlaterstages.AnimalModel:MC38tumor-bearingBALB/cfemalemice(8weeks)[1].Dosage:10mg/kgAdministration:Dailyintraperitonealinjection(i.p.),atthecorrespondingdosesfor16days.Result:Demonstrated19.24%tumorgrowthinhibition(TGI)withoutstatisticalsignificanceandcausednobodyweightchangesinmice.Exhibitedsignificantlyattenuatedantitumorefficacyinimmunodeficientmice,suggestingimmunemicroenvironment-dependenttherapeuticactivity.DemonstratedsignificantlyincreasedproportionsofCD8+TcellsandelevatedCD8+/CD4+ratios,whileexhibitingupwardtrendsinNKcellproportionswithunchangedTregs/MDSCsratios,collectivelyindicatingtumorimmunemicroenvironmentremodeling.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].XianZhang,etal.DiscoveryofindaneandnaphthalenederivativesasUSP7inhibitors.EurJMedChem.2025May29.295:117824.McePdfHeightCaution:Pro