Palbociclib-orotate-PD-0332991-orotate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPalbocicliborotateCat.No.:HY-50767DSynonyms:PD0332991orotate分⼦式:C₂₉H₃₃N₉O₆分⼦量:603.63作⽤靶点:CDK作⽤通路:CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Palbociclib(PD0332991)orotate⼀种具有⼝服活性的CDK4和CDK6选择性抑制剂，IC50值分别为11nM和16nM。Palbocicliborotate对癌细胞具有抗增殖活性，并诱导其细胞周期阻滞，可⽤于HR阳性和HER2阴性乳腺癌，以及肝细胞癌的相关研究[1][3][4]。IC50&TargetCdk4/cyclinD3Cdk4/cyclinD1Cdk6/cyclinD2DYRK1A9nM(IC50)11nM(IC50)16nM(IC50)2000nM(IC50)MAPK8000nM(IC50)体外研究Palbociclib(0-1μM,24h)orotateinhibitsretinoblastomaphosphorylationatSer795inMDA-MB-435cellswithanIC50valueof0.063μM,andobtainssimilareffectsonbothSer780andSer795phosphorylationintheColo-205coloncarcinoma[1].Palbociclib(0-10μM,24h)orotatearrestsMDA-MB-453cellsexclusivelyinG1phase[1].Palbociclib(500nM,7days)orotateincreasesexpressionofhomologousgenes(H2d1,H2k1,andB2m)inMDA-MB-453andMDA-MB-361cells[2].Palbociclib(0-1μM,6days)orotateinhibitsgrowthofseveralluminalER-positiveaswellasHER2-amplifiedbreastcancercelllines,withIC50valuesrangingfrom4nMto1μM[3].Palbociclib(0-1μM,3days)orotateinhibitstheproliferationofhumanlivercancercelllineswithIC50valuesrangingfrom0.01μMto3.49μM,andinducesareversiblecellcyclearrest[4].CellProliferationAssay[3]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:ER-positiveaswellasHER2-amplifiedbreastcancercelllines(MDA-MB-175,ZR-75-30,CAMA-1,etc.)Concentration:0-1μMIncubationTime:6daysResult:InhibitedgrowthofluminalER-positiveaswellasHER2-amplifiedbreastcancercelllines.CellCycleAnalysissup>[1]CellLine:MDA-MB-453cellsConcentration:0-1μMIncubationTime:24hResult:ArrestedMDA-MB-453cellsinG1.体内研究Palbociclib(oraladminstration,75or150mg/kg,dailyfor14days)orotateproducesrapidtumorregressionsanddelaystumorgrowth[1].Palbociclib(oraladminstration,90mg/kg,dailyfor12days)orotatereducesTregnumbersandtheTreg:CD8ratiointhespleenandlymphnodesintumor-freemice,demonstratingthetumor-independenteffects[2].Palbociclib(oraladministration,100mg/kg,dailyfor1week)orotatehaspotentantitumoureffectsingeneticallyengineeredmosaicmousemodeloflivercancer[4].AnimalModel:MicebearingColo-205coloncarcinomaxenografts(p16deleted)[1]Dosage:75,150mg/kgAdministration:Oraladministration;dailyfor14daysResult:Producedrapidtumorregressionsandacorrespondingtumorgrowthdelayof~50days.AnimalModel:Tumor-freefemaleFVBmice[2]Dosage:90mg/kgAdministration:Oraladministration;dailyfor12daysResult:ReducedtotalthymicmassandimmatureCD4+andCD8+double-positivethymocytes,andincreasedthefractionsofCD4+andCD8+single-positivethymocytes.AnimalModel:Geneticallyengineeredmosaicmousemodeloflivercancer(Myc;p53-sgRNA)[4]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:100mg/kgAdministration:Oraladministration;dailyfor1weekResult:Decreasedtheluminescencesignalinliveranddelayedtumourgrowth.户使⽤本产品发表的科研⽂献•Nature.2020Jul;583(7817):620-624.•Nature.2017Aug24;548(7668):471-475.•Nature.2017Jun15;546(7658):426-430.•NatMethods.2022Mar;19(3):331-340.•CancerCell.2017Apr10;31(4):576-590.e8.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].FryDW,etal.Specificinhibitionofcyclin-dependentkinase4/6byPD0332991andassociatedantitumoractivityinhumantumorxenografts.MolCancerTher.2004Nov;3(11):1427-38.[2].GoelS,etal.CDK4/6inhibitiontriggersanti-tumourimmunity.Nature.2017Aug24;548(7668):471-475.[3].RichardSFinn,etal.PD0332991,aselectivecyclinDkinase4/6inhibitor,preferentiallyinhibitsproliferationofluminalestrogenreceptor-positivehumanbreastcancercelllinesinvitro.BreastCancerRes.2009;11(5):R77.[4].BollardJ,etal.Palbociclib(PD-0332991),aselectiveCDK4/6inhibitor,restrictstumourgrowthinpreclinicalmodelsofhepatocellularcarcinoma.Gut.2017Jul;66(7):1286-12