LLK203-DataSheet-生命科學試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemELLK203Cat.No.:HY-162312CASNo.:2758090-62-7分子式:C??H??N?O?S?分子量:561.69作用靶點:Deubiquitinase;Apoptosis作用通路:CellCycle/DNADamage;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性LLK203是一種有效的USP2/USP8雙靶點抑制劑，IC50分別為0.89μM和0.52μM。LLK203導致ERα降解并誘導乳腺癌MCF-7細胞凋亡。LLK203對4T1腫瘤小鼠模型具有抗腫瘤活性。IC50&TargetUSP2USP80.89μM(IC50)0.52μM(IC50)體外研究LLK203(0-100μM;36h)demonstrateshighinhibitoryactivityonMCF-7cells(IC50=3.4μM)comparedwithML364(IC50=9.3μM).LLK203demonstratesa4-foldincreaseinUSP2activityanda9-foldincreaseinUSP8activitycomparedtoML364(HY-100900)[1].LLK203(10-50μM;24h)increasestheratioofapoptoticcellsandremaineslargelyinG1phasonMCF-7cells[1].LLK203(2-50μM;24h)candegradevariousproteins(MDM2,CyclinD1,Her2,ERα)inadosedependentmanner[1].LLK203(2-50μM;for7days)showsarobustabilityofinhibitingcloneformationattheconcentrationof10μM[1].CellCytotoxicityAssay[1]CellLine:MCF-7andMCF10AcellsConcentration:0-100μMIncubationTime:36h1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:Exhibitedlowercytotoxicitytowardsnormalcells(MCF10A;IC50=20.4μM),whiledemonstratinghigherinhibitoryactivityonBCcells(MCF-7;IC50=3.4μM).ApoptosisAnalysis[1]CellLine:MCF-7cellsConcentration:10,30,50μMIncubationTime:24hResult:Increasedtheratioofapoptoticcells.CellCycleAnalysis[1]CellLine:MCF-7cellsConcentration:10,30,50μMIncubationTime:24hResult:RemainedlargelyinG1phase.WesternBlotAnalysis[1]CellLine:MCF-7cellsConcentration:2,5,10,30,50μMIncubationTime:24hResult:Coulddegradevariousproteins(MDM2,CyclinD1,Her2,ERα)inadosedependentmanner.體內(nèi)研究LLK203(20mg/kg;Intraperitoneal;everyday;for23days)significantlyreducestumorgrowthina4T1tumor-bearingmicemodel[1].PharmacokineticParametersofLLK203inmaleSprague-Dawleyrats[1].Intravenously(5mg/kg)Orally(50mg/kg)Tmax(h)6Cmax(ng/mL)366301572AUC0-t(h?ng/mL)6082419144T1/2(h)206.14CL(mL/h/kg)58F(%)2.2%AnimalModel:BALB/cmicesubcutaneouslyinoculatedwith4T1cells[1]Dosage:20mg/kgAdministration:Intraperitoneal;everyday;for23daysResult:Significantlyreducedtumorgrowthina4T1tumor-bearingmicemodel.REFERENCES2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEYuchengTian,etal.ThediscoveryofpotentUSP2/USP8dual-targetinhibitorsforthetreatmentofbreastcancerviastructureguidedoptimizationofML364.EuropeanJournalofMedicinalChemistry.Volume268,15March2024,116275.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappli