Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEITK-IN-6Cat.No.:HY-174903CASNo.:2616666-32-9分?式:C??H??Cl?N?O?S分?量:451.32作?靶點:Itk作?通路:ProteinTyrosineKinase/RTK儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性ITK-IN-6?種?效的有選擇性的ITK抑制劑(Kd=387nM)。ITK-IN-6直接結(jié)合到ITK激酶結(jié)構(gòu)域。ITK-IN-6阻?促炎細胞因?釋放以及Th2和Th17細胞的活化與分化。ITK-IN-6通過減輕炎癥細胞浸潤、減少黏液和IgE?成來改哮喘進展。ITK-IN-6顯著抑制?道炎癥，?于哮喘研究[1]。體外研究ITK-IN-6(CompoundC-161)(24h)inhibitsITKdownstreamtranscriptionalactivityinJurkat-NFAT-Lucstablecelllinewithaninhibitionrateof62.27%[1].ITK-IN-6(0.07-5μM,12h)C-161hasgoodsafetyateffectivedosesinCD4+Tcells,attenuatesTh2andTh17differentiationinvitro[1].ITK-IN-6(0.15-2.5μM,12h)blockskeyfactorsforTcellactivationandinhibitsTcellsurfaceactivationmarkersinJurkatcells[1].ITK-IN-6(0.625-2.5μM,12h)specificallyinhibitsITKinJurkatTcellsandblocksthecellularandmolecularactivationpotentialofTcellreceptorproximalsignaling,andtheexpressionofCD69issignificantlysuppressed[1].ITK-IN-6(0.15-2.5μM)inhibitsIL-2expressionatboththetranscriptionalandproteinlevelsinadose-dependentmanner,withanIC50of494nMinJurkatcells[1].ITK-IN-6(0.625-2.5μM,30min)treatmentofJurkatcellssignificantlyreducesintracellularCa2+fluxinducedbyanti-CD3[1].WesternBlotAnalysis[1]CellLine:JurkatTcellsConcentration:0.625μM,1.25μM,2.5μM1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:12hResult:Inhibitedthephosphorylationofp-PLCγ1,p-IκBα,p-NF-κB,andp-ERKinadose-dependentmannerbyC-161,whereasthephosphorylationofupstreamZAP70remainedunchanged.CellDifferentiationAssay[1]CellLine:CD4TcellsConcentration:0.07μM,0.15μM,0.3μM,1.25μM,2.5μM,5μMIncubationTime:4days(Th2);3days(Th17)Result:InhibitedIL-4productionbyTh2cellsinadose-dependentmanner,andnocytotoxiceffectwasobserved.SignificantlyreducedthepercentageofcellsproducingIL-17Aatarelativelyhighconcentration(1.25μM),butwasaccompaniedbymildcytotoxicity.InhibitedthedifferentiationofnaiveCD4+TcellsintoTh2cellsandsignificantlyreducedthepercentageofcellsproducingIL-17A.體內(nèi)研究ITK-IN-6(CompoundC-161)(10mg/kg,i.p,Oncedailyfor7to11days)significantlyalleviatesairwayinflammationinC57BL/6Jmiceinducedbyhousedustmites(HDM)byinhibitingTh2/Th17differentiationandcytokineproduction,withgoodsafety[1].AnimalModel:HDM-inducedasthmaC57BL/6Jmicemodel(6-8weeks,18-20g)[1]Dosage:10mg/kgAdministration:Intraperitonealinjection(i.p.),7to11daysafterHDMsensitization,onceaday,onehourbeforeHDMchallenge.Result:Reducedthetotalnumberofinflammatorycells,eosinophils(EOS),neutrophils(NEU),andBcellsinBALF,alleviatedinflammatoryinfiltrationandmucussecretioninlungtissue,anddecreasedserumtotalIgEandHDM-specificIgElevels.ReducedCD3Tcellinfiltrationinlungtissue,decreasedtheproportionandnumberofCD4Tcellsinthelung,anddownregulatedthemRNAandproteinlevelsofTh2/Th17-relatedcytokines(IL-4/IL-5/IL-13/IL-17A)inlungtissue.Causednoweightlossordeathinmice,andresultedinnoabnormalitiesinorganindexes,serumbiochemicalindicators,ortissuepathology.REFERENCES[1].ZhaoxiGuo,etal.ANovelSmallMoleculeITKInhibitorSuppressesTh2/Th17DifferentiationandAttenuatesAirwayInflammationina2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMouseModelofHDM-InducedAsthma.Immunology.2025Jun12.McePdfHeightCaution:Produ