Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPalbociclibisethionateCat.No.:HY-A0065CASNo.:827022-33-3Synonyms:PD0332991isethionate分?式:C??H??N?O?S分?量:573.66作?靶點:CDK作?通路:CellCycle/DNADamage儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數據體外實驗H2O:50mg/mL(87.16mM;Needultrasonic)DMSO:10mg/mL(17.43mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7432mL8.7160mL17.4319mL5mM0.3486mL1.7432mL3.4864mL10mM0.1743mL0.8716mL1.7432mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥1mg/mL(1.74mM);ClearsolutionBIOLOGICALACTIVITY?物活性Palbociclib(PD0332991)isethionate?種具有?服活性的CDK4和CDK6選擇性抑制劑，IC50值分別為11nM和16nM。Palbociclibdihydrochloride對癌細胞具有抗增殖活性，并誘導其細胞周期阻滯，可?于HR陽性和HER2性乳腺癌，以及肝細胞癌的相關研究[1][3][4]。IC50&TargetCdk4/cyclinD3Cdk4/cyclinD1Cdk6/cyclinD2DYRK1A9nM(IC50)11nM(IC50)16nM(IC50)2000nM(IC50)MAPK8000nM(IC50)體外研究Palbociclibdihydrochloride(0-1μM,24h)inhibitsRbPhosphorylationatSer795inMDA-MB-435cellswithanIC50valueof0.063μM,andobtainssimilareffectsonbothSer780andSer795phosphorylationintheColo-205coloncarcinoma[1].Palbociclibdihydrochloride(0-10μM,24h)arrestsMDA-MB-453cellsexclusivelyinG1phase[1].Palbociclibdihydrochloride(500nM,7days)increasesexpressionofhomologousgenes(H2d1,H2k1,andB2m)inMDA-MB-453andMDA-MB-361cells[2].Palbociclibdihydrochloride(0-1μM,6days)inhibitsgrowthofseveralluminalER-positiveaswellasHER2-amplifiedbreastcancercelllines,withIC50valuesrangingfrom4nMto1μM[3].Palbociclibdihydrochloride(0-1μM,3days)inhibitstheproliferationofhumanlivercancercelllineswithIC50valuesrangingfrom0.01μMto3.49μM,andinducesareversiblecellcyclearrest[4].CellCycleAnalysis[1]CellLine:MDA-MB-453cellsConcentration:0-1μMIncubationTime:24hResult:ArrestedMDA-MB-453cellsinG1.CellProliferationAssay[3]CellLine:ER-positiveaswellasHER2-amplifiedbreastcancercelllines(MDA-MB-175,ZR-75-30,CAMA-1,etc.)Concentration:0-10μMIncubationTime:6daysResult:InhibitedgrowthofluminalER-positiveaswellasHER2-amplifiedbreastcancercelllines.2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體內研究Palbociclibisethionate(oraladminstration,75or150mg/kg,dailyfor14days)producesrapidtumorregressionsanddelaystumorgrowth[1].Palbociclibisethionate(oraladminstration,90mg/kg,dailyfor12days)reducesTregnumbersandtheTreg:CD8ratiointhespleenandlymphnodesintumor-freemice,demonstratingthetumor-independenteffects[2].Palbociclibisethionate(oraladministration,100mg/kg,dailyfor1week)haspotentantitumoureffectsingeneticallyengineeredmosaicmousemodeloflivercancer[4].AnimalModel:MicebearingColo-205coloncarcinomaxenografts(p16deleted)[1]Dosage:75,150mg/kg,dailyfor14daysAdministration:OraladminstrationResult:Producedrapidtumorregressionsandacorrespondingtumorgrowthdelayof~50days.AnimalModel:Tumor-freefemaleFVBmice[2]Dosage:90mg/kg(dilutedin50nMsodiumD-lactate),dailyfor12daysAdministration:OraladminstrationResult:ReducedtotalthymicmassandimmatureCD4+andCD8+double-positivethymocytes,andincreasedthefractionsofCD4+andCD8+single-positivethymocytes.AnimalModel:Geneticallyengineeredmosaicmousemodeloflivercancer(Myc;p53-sgRNA)[4]Dosage:100mg/kg,dailyfor1week.Administration:OraladminstrationResult:Decreasedtheluminescencesignalinliveranddelayedtumourgrowth.戶使?本產品發表的科研?獻?Nature.2020Dec;588(7836):169-173.?Nature.2020Jul;583(7817):620-624.?Nature.2017Aug24;548(7668):471-475.?Nature.2017Jun15;546(7658):426-430.?NatMethods.2022Mar;19(3):331-340.Seemorecustomervalidationsonwww.MedChemEREFERENCES3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[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,restrictstumourgrowthinpreclinicalmodelsofhepatoc