Obatoclax-GX15-070-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEObatoclaxCat.No.:HY-10969ACASNo.:803712-67-6Synonyms:GX15-070分⼦式:C₂₀H₁₉N₃O分⼦量:317.38作⽤靶点:Bcl-2Family;Autophagy;Parasite作⽤通路:Apoptosis;Autophagy;Anti-infection储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCOA.BIOLOGICALACTIVITY⽣物活性Obatoclax(GX15-070)BH3模拟物，泛BCL-2家族蛋⽩抑制剂，对BCL-2的Ki值为220nM。Obatoclax诱导⾃噬(autophagy)依赖性细胞死亡，并靶向细胞周期蛋⽩D1进⾏蛋⽩酶体降解。Obatoclax具有抗癌和⼴谱抗寄⽣⾍(antiparasitic)活性。IC50&TargetBCL2Mcl-1Bcl-xLBcl-W200nM(Ki)1-7μM(Ki)1-7μM(Ki)1-7μM(Ki)Bcl-B1-7μM(Ki)体外研究Obatoclax(GX15-070)inhibitsBCL-2,BCL-XL,MCL-1,BCL-w,A1,andBCL-bwithKivalues≈1-7μM[2].Obatoclax(50-200nM;24-72hours)inducesadose-andtime-dependentreductionofcellnumbersinallhumancolorectalcancercelllines.Inparticular,theIC50ofcellproliferationat72hare25.85,40.69,and40.01nMforHCT116,HT-29,andLoVocells,respectively[1].Obatoclax(400nM;for24hours)inducesautophagyinOSCCcells[3].Obatoclax(50-200nM;for24hours)provokesadose-dependentincreaseintheG1-phasecellpopulations[1].Obatoclax(25-200nM;for24hours)indicatesamarkeddropincyclinD1levelsaslowas50nM[1].ObatoclaxinducesT286phosphorylation-dependentor-independentcyclinD1degradation.inHCT116andLoVocells,thesteady-statelevelsofp-CyclinD(T286)begantodeclineonceexposedtoobatoclax(200nM;1,3,6,12,24hours).ObatoclaxinhibitsGSK3βbutactivatesp38MAPK,whilebarelyaffectingERK1/2activityinHT-29cells[1].1/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEObatoclax(50,100,150,200,250,300,350,400,450nM)potentlyinhibitstheclonogenicpotentialoforalcancercells[1].CellProliferationAssay[1]CellLine:humancolorectalcancerHCT116,HT-29andLoVocellsConcentration:50,100,200nMIncubationTime:24,48,and72hoursResult:Inducedadose-andtime-dependentreductionofcellnumbers.CellAutophagyAssay[3]CellLine:AW8507andSCC029BcellsConcentration:400nMIncubationTime:24hoursResult:InducedautophagyinOSCCcells.CellCycleAnalysis[1]CellLine:HCT116andHT-29cellsConcentration:50,100,200nMIncubationTime:24hoursResult:Provokedadose-dependentincreaseintheG1-phasecellpopulations.WesternBlotAnalysis[1]CellLine:HCT116,HT-29andLoVocellsConcentration:50,100,200nMIncubationTime:24hoursResult:IndicatedamarkeddropincyclinD1levelsaslowas50nM.体内研究Obatoclax(GX15-070;1.15-5mg/kg;intravenouslyinjected;fiveconsecutivedays)exhibitspotentantitumoractivityinxenograftmousemodelsinadose-dependentmanner[4].AnimalModel:6-8weeksoldfemaleBALB/Cnudemicebearingsubcutaneoustumors[4]Dosage:1.15,2.5,5mg/kg2/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:Intravenouslyinjected(throughlateraltailvein);fiveconsecutivedays(i.e.5injections)Result:Exhibitedpotentantitumoractivityinxenograftmousemodelsinadose-dependentmanner.•AmJCancerRes.2019Mar1;9(3):546-561.•BiomedPharmacother.2020Jun18;129:110371.•SciRep.2019Sep24;9(1):13786.•ResearchSquarePreprint.2020Sep.•DepartamentodeBiotecnología-DepartamentdeBiotecnologia.2020Sep7.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].OrCR,etal.Obatoclax,aPan-BCL-2Inhibitor,TargetsCyclinD1forDegradationtoInduceAntiproliferationinHumanColorectalCarcinomaCells.IntJMolSci.2016Dec27;18(1).[2].SulkshaneP,etal.BH3mimeticObatoclax(GX15-070)mediatesmitochondrialstresspredominantlyviaMCL-1inhibitionandinducesautophagy-dependentnecroptosisinhumanoralcancercells.Oncotarget.2016Aug5;8(36):60060-60079.[3].EhrenkauferG,etal.Identificationofanisomycin,prodigiosinandobatoclaxascompoundswithbroad-spectrumanti-parasiticactivity.PLoSNeglTropDis.2020Mar20;14(3):e0008150.[4].NguyenM,etal.Smallmoleculeobatoclax(GX15-070)antagonizesMCL-1andovercomesMCL-1-mediatedresistancetoapoptosis.ProcNatlAcadSciUSA.2007Dec4;104(49):19512-7.Epub2007Nov2