Topo-I-COX-2-IN-2-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETopoI/COX-2-IN-2Cat.No.:HY-150755分⼦式:C₂₄H₂₅ClN₄O分⼦量:420.93作⽤靶点:Topoisomerase;COX;Apoptosis;ReactiveOxygenSpecies作⽤通路:CellCycle/DNADamage;Immunology/Inflammation;Apoptosis;MetabolicEnzyme/Protease;NF-κB储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性TopoI/COX-2-IN-2(CompoundW10)⼀种有效的TopoI和COX-2的双靶点抑制剂，IC50值分别为0.90μM和2.31μM。TopoI/COX-2-IN-2通过线粒体途径诱导癌细胞凋亡（apoptosis）。IC50&TargetTopoisomeraseICOX-20.90μM(IC50)2.31μM(IC50)体外研究TopoI/COX-2-IN-2(CompoundW10)(0-30μM)showsgoodtoxicityagainstcancercells[1].TopoI/COX-2-IN-2formsanionicbondinginteractionwithDA13ofDNAtoimproveTopoIinhibition[1].TopoI/COX-2-IN-2(0-9μM,24h)arrestscellcycleofHT29andRKOatG1/G0phase,inducesapoptosisinHT29andRKOcellsthroughthemitochondrialpathway,andinhibitsabnormalactivationoftheNF-κB/IκBpathway.[1].CellProliferationAssay[1]CellLine:HT29,RKO,HCT116,LoVoandSW480Concentration:0-30μMIncubationTime:72hResult:ShowedgoodtoxicitywithIC50valuesof1.48±0.08μM,2.06±0.01μM,4.89±0.36μM,8.42±0.22μMand7.36±0.64μMforHT29,RKO,HCT116,LoVoandSW480cells,respectively.CellCycleAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:HT29andRKOConcentration:2,4and8μMforHT29;3,6and9μMforRKOIncubationTime:24hResult:BlockedthecellcycleinG1/G0phaseinbothHT29andRKO.InHT29cells,thearrestingactivitywasnotobviousfortheratioofG1/G0phaseinhigh-concentrationtreatmentgroupincreasedfrom55.20%to65.17%slightly,whileinRKOcells,theratioofG1/G0phaseobviouslyincreasedfrom37.57%to76.99%.ApoptosisAnalysis[1]CellLine:HT29andRKOConcentration:2,4and8μMforHT29;3,6and9μMforRKOIncubationTime:24hResult:MainlyinducedthelateapoptosisinHT29cellsandexhibiteddualinductionoflateandearlyapoptosisinRKOcells.Inducedtheproductionofreactiveoxygenspecies(ROS)burstandsignificantlyreducethemitochondrialmembranepotential.WesternBlotAnalysis[1]CellLine:HT29andRKOConcentration:2,4and8μMforHT29;3,6and9μMforRKOIncubationTime:24hResult:Inducedincreasedexpressionofthepro-apoptoticproteinsBax,cytochromecandapoptoticeffectorcleavedcaspase3/9,reducedtheexpressionoftheinhibitoryfactorBcl-2.TheexpressionsofphosphorylatedNF-κBandIκBweresignificantlydecreased.体内研究TopoI/COX-2-IN-2(CompoundW10)(15and30mg/kg;i.p.;b.i.dfor2weeks)inhibitstumorgrowthandshowsobviousnecrosisontumortissue[1].TopoI/COX-2-IN-2hasacceptablepharmacokineticpropertiesforintraperitonealinjectionandoraladministration[1].AnimalModel:MaleBALB/cnudemiceweighing20–25g,HT29xenograftmodel[1]Dosage:15and30mg/kg2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:Intraperitonealinjection,twicedailyfor2weeksResult:30mg/kggroupimmediatelysloweddownthetumorgrowthrateafteradministration,andalmostcompletelypreventedtumorgrowthinthelaterstage,anditstumorgrowthinhibition(TGI)was57.86%.15mg/kggroupshowed40.67%TGI.Showedobviousnecrosisontumortissue.AnimalModel:250–280gmaleSDrats[1]Dosage:100mg/kgand30mg/kgAdministration:Intragastricadministration(100mg/kg)orintraperitonealinjection(30mg/kg)(PharmacokineticsStudy)Result:PharmacokineticdataofTopoI/COX-2-IN-2(W10)invivoa[1]Comp.Dose(mg/kg)RouteT1/2(h)Tmax(h)Cmax

(μg/mL)AUC0-t(μg⋅h/mL)TopoI/COX-2-IN-2100p.o.8.87±1.923.67±0.582.00±0.4124.81±5.7630i.p.4.27±0.220.28±0.051.60±0.345.41±0.20aTopoI/COX-2-IN-2wasadministeredto6SDratswithdifferentadministrationmethodsanddoses,andtheserumconcentrationwasanalyzed.TheanalysismethodisthelineartrapezoidalPKsolver2.0computerprogramofthenon-compartmentalmodel.Allthedataarefromtheabove6rats,andthedataarerepresentedbythemeanandstandarddeviation.REFERENCES[1].HuX,etal.DiscoveryofdualinhibitorsoftopoisomeraseIandCyclooxygenase-2forcoloncancertherapy.EurJMedChem.2022Jun23;240:11