Plogosertib-CYC140-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPlogosertibCat.No.:HY-147298CASNo.:1137212-79-3Synonyms:CYC140分⼦式:C₃₄H₄₈N₈O₃分⼦量:616.8作⽤靶点:Polo-likeKinase(PLK)作⽤通路:CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Plogosertib(CYC140)⼀种选择性的、有效的、具有⼝服活性的ATP竞争性的PLK1抑制剂(IC50:3nM)。Plogosertib⼀种有抗增殖活性的抗癌剂，可⽤于多种肿瘤的研究，包括⾷管癌、胃癌、⽩⾎病、⾮⼩细胞肺癌、巢癌和鳞状细胞癌。IC50&TargetPLK1PLK2PLK33nM(IC50)149nM(IC50)393nM(IC50)体外研究Plogosertib(CYC140)selectivelyinhibitsPLK1(IC50:3nM),andis>50foldmorepotentagainstPLK2andPLK3(IC50s:149nMand393nM,respectively)[2].Plogosertib(0-4μΜ,2h)reducesphosphorylationofthePLK1substrate,pSer4-nucleophosmin(p-NPM)inKYSE-410cells[2].Plogosertib(100nM,24h)increasesintheproportionofmitoticcells,withincreasedmonopolarspindlesinHeLacells[2].Plogosertib(72h)preferentiallyinhibitscellproliferationinmalignantcelllines(IC50s:14-21nM),andislesstoxicagainstnone-malignantcelllines(IC50:82nM)[2].CellProliferationAssay[2]CellLine:KYSE-410cellsConcentration:0,0.07,0.15,0.3,0.6,1.25μΜ1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:72hResult:Inhibitedcellproliferationinaconcentration-dependentmanner.WesternBlotAnalysis[2]CellLine:KYSE-410cellsConcentration:0,0.01,0.025,0.05,0.1,0.25,0.5,1,2,4μΜIncubationTime:2h(p-NPM),24h(p-HH3),72h(cPARP)Result:ReducedphosphorylationofthePLK1substrate(p-NPM).IncreasedinthemitoticmarkerpSer10histoneH3(p-HH3),andthecleavageofPARP(cPARP,anindicatorofcelldeath).体内研究Plogosertib(CYC140,oraladministration,40mg/kg,qd5/2/5)inhibitstumorgrowthinpreclinicalxenograftmodelsofacuteleukemiaandsolidtumors[2].Plogosertib(CoumpondA7,1mg/kg,mouse)showspharmacokineticparameters:Cmax(453ng/mL),AUC(377hr•ng/mL),Cl(2445mL/h/kg)[3].AnimalModel:HL60promyelocyticleukemiaxenograft[2]Dosage:40,54,67mg/kg,qd5/2/5Administration:OraladministrationResult:Inhibitedtumorgrowth(>87%)withoutsignificantlossinbodyweight.AnimalModel:OE19esophagealxenograft[2]Dosage:40mg/kg,qd5/2Administration:OraladministrationResult:Inhibitedtumorgrowth(61%inhibition).REFERENCES[1].SylvieMoureau,etal.Abstract4178:ThenovelPLK1inhibitor,CYC140:Identificationofpharmacodynamicmarkers,sensitivetargetindicationsandpotentialcombinations.CancerRes(2017)77(13_Supplement):4178.[2].MoureauS,etal.TherapeuticpotentialofnovelPLK1inhibitorCYC140inesophagealcancerandacuteleukemia[J].EuropeanJournalofCancer,2016,1(69):S117.[3].SusanDavis,etal.Treatmentofproliferativediseaseswithpyrimidodiazepinones.PatentUS20150320762A1.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotbeenfullyvalidatedforme