Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEALK/ROS1-IN-5Cat.No.:HY-170418分?式:C??H??F?N?O?分?量:554.59作?靶點:Anaplasticlymphomakinase(ALK);ROSKinase;Apoptosis作?通路:ProteinTyrosineKinase/RTK;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性ALK/ROS1-IN-5(compoundX4)?種ALK和ROS1激酶選擇性抑制劑，IC50分別為0.512(ALK)，0.766μM(ROS1)。ALK/ROS1-IN-5抑制H2228細胞，IC50為0.034μM。ALK/ROS1-IN-5以劑量依賴性?式誘導癌細胞apoptosis。ALK/ROS1-IN-5有效抑制癌細胞中p-ALK和p-ERK的表達。體外研究ALK/ROS1-IN-5(0-100μM,72h)exhibitssuperiorinhibitoryactivityagainstbothH2228,H1975andH460cells[1].ALK/ROS1-IN-5(10μM)exhibitsnotableinhibitoryactivityagainstmembersofthetyrosinekinasefamily,includingEGFR,AKT1,FGFR1andERK1[1].ALK/ROS1-IN-5(10μM)demonstratessignificantkinaseinhibitoryactivityagainstALKandROS1,withinhibitionratesof94.34%and94.27%,respectively[1].ALK/ROS1-IN-5(1-2μM,24h)inhibtscellmigrationinH2228cellsdose-dependently[1].ALK/ROS1-IN-5(1-2μM,24h)inducesapoptosisandcellcyclearrestinH2228cellsdose-dependently[1].ALK/ROS1-IN-5(1-2μM,24h)inducesinH2228cellsdose-dependently[1].ALK/ROS1-IN-5(0.1-0.5μM,24h)reducedthephosphorylationofALKandERKinadose-dependentmanner[1].CellCycleAnalysis[1]CellLine:H2228cellsConcentration:1,2μMIncubationTime:24hResult:SignificantlyarrestedthecellcycleofH2228cellsintheSphase,exhibitingaclear1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEconcentration-dependenteffect.CellMigrationAssay[1]CellLine:H2228cellsConcentration:1,2μMIncubationTime:24hResult:Dose-dependentlyandeffectivelyinhibitedwoundhealinginH2228cells.CellProliferationAssay[1]CellLine:H2228,H1975,H460cellsConcentration:0-100μMIncubationTime:72hResult:InhibitedH460andH2228cellswithIC50of0.21μMand0.034μMrespectively.ApoptosisAnalysis[1]CellLine:H2228cellsConcentration:1,2μMIncubationTime:24hResult:Showeda10.0%latecellapoptosisratecomparedtoEntrectinib(HY-12678)atthesame2μMdoseofthepositivedrug.SignificantlypromotedapoptosisinH2228cellsinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:H2228cellsConcentration:0.1,0.2,0.5μMIncubationTime:24hResult:ReducedthephosphorylationofALKandERKinadosedependentmanner.Notonlyeffectivelyinhibitedtheexpressionofp-ALKinH2228cells,butalsoinhibitedtheexpressionofp-ERK,apathwaydownstreamofALKandROS1kinase.體內研究ALK/ROS1-IN-5(60,120mg/kg,p.o.,daily,7days)exhibitsnosignificanttoxicityinbiochemicalbloodsamplesinmice[1].2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEALK/ROS1-IN-5(10mg/kg,p.o.,daily,35days)demonstratesgreatantitumoreffect[1].ALK/ROS1-IN-5(5-25mg/kg,p.o.,daily,14days)hasminimalimpactonRET(reductionofthereticulocyte)[1].ALK/ROS1-IN-5(25-50mg/kg,p.o.,daily,21days)exhibitsalowertumorvolumegrowthratethanthepositivecontrolgroup[1].ALK/ROS1-IN-5decreasesKi67,Bcl2,Caspase3andPCNAinadose-dependentmannerasthedosage[1].AnimalModel:KMmice[1].Dosage:60,120mg/kgAdministration:p.o.,daily,7daysResult:Exhibitednosignificanttoxicity.AnimalModel:H2228tumor-bearingnudemice[1].Dosage:10mg/kgAdministration:p.o.,daily,35daysResult:Incombinationwithweekly37.5mg/kgCarboplatin(HY-17393)demonstratedgreatimprovementoftheantitumoreffectcomparedtocarboplatinmonotherapy(94.7%TGIvs69.7%TGI).Inducednosignificantbodyweightlossduringthestudy.AnimalModel:H2228tumor-bearingnudemice[1].Dosage:5,25mg/kgAdministration:p.o.,daily,14daysResult:HadminimalimpactonRET(reductionofthereticulocyte).Inducednosignificantbodyweightlossduringthestudy.AnimalModel:H2228tumor-bearingnudemice[1].Dosage:25,50mg/kgAdministration:p.o.,onceevery48h,21daysResult:Exhibitedalowertumorvolumegrowthratethanthepositivecontrolgroup.Exhibitedatumorinhibitionrategreaterthan30%.REFERENCES3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].HuangX,etal.Revealing5-(3,5-difluorobenzyl)-1H-indazoleastheactivepharmacophoreofALK/ROS1dualinhibitorsthroughtheoreticalcalculationsandbiologicalactivityevaluations.BioorgChem.2025Ja