Palbociclib-monohydrochloride-PD-0332991-monohydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPalbociclibmonohydrochlorideCat.No.:HY-50767ACASNo.:827022-32-2Synonyms:PD0332991monohydrochloride分?式:C??H??ClN?O?分?量:483.99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(shù)據(jù)體外實驗H2O:7.14mg/mL(14.75mM;ultrasonicandwarmingandheatto60°C)DMSO:4.63mg/mL(9.57mM;ultrasonicandwarmingandheatto80°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0662mL10.3308mL20.6616mL5mM0.4132mL2.0662mL4.1323mL10mM0.2066mL1.0331mL2.0662mL請根據(jù)產(chǎn)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(fù)凍融造成的產(chǎn)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(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?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(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(xiàn)沉淀、析出現(xiàn)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：0.5%HPMC>>1%Tween801/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:20mg/mL(41.32mM);Clearsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥0.54mg/mL(1.12mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥0.54mg/mL(1.12mM);Clearsolution4.請依序添加每種溶劑：Lacticacidbuffer(50mM,pH4.0)Solubility:4.17mg/mL(8.62mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Palbociclib(PD0332991)monohydrochloride?種具有?服活性的CDK4和CDK6選擇性抑制劑，IC50值分別為11nM和16nM。Palbociclibmonohydrochloride對癌細胞具有抗增殖活性，并誘導(dǎo)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(guān)研究。IC50&TargetCdk4/cyclinD3Cdk4/cyclinD1Cdk6/cyclinD2DYRK1A9nM(IC50)11nM(IC50)16nM(IC50)2000nM(IC50)MAPK8000nM(IC50)體外研究Palbociclibmonohydrochloride(0-1μM,24h)inhibitsRbPhosphorylationatSer795inMDA-MB-435cellswithanIC50valueof0.063μM,andobtainssimilareffectsonbothSer780andSer795phosphorylationintheColo-205coloncarcinoma[1].Palbociclibmonohydrochloride(0-10μM,24h)arrestsMDA-MB-453cellsexclusivelyinG1phase[1].Palbociclibmonohydrochloride(500nM,7days)increasesexpressionofhomologousgenes(H2d1,H2k1,andB2m)inMDA-MB-453andMDA-MB-361cells[2].Palbociclibmonohydrochloride(0-1μM,6days)inhibitsgrowthofseveralluminalER-positiveaswellasHER2-amplifiedbreastcancercelllines,withIC50valuesrangingfrom4nMto1μM[3].Palbociclibmonohydrochloride(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.)2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:0-10μMIncubationTime:6daysResult:InhibitedgrowthofluminalER-positiveaswellasHER2-amplifiedbreastcancercelllines.體內(nèi)研究Palbociclibmonohydrochloride(oraladminstration,75or150mg/kg,dailyfor14days)producesrapidtumorregressionsanddelaystumorgrowth[1].Palbociclibmonohydrochloride(oraladminstration,90mg/kg,dailyfor12days)reducesTregnumbersandtheTreg:CD8ratiointhespleenandlymphnodesintumor-freemice,demonstratingthetumor-independenteffects[2].Palbociclibmonohydrochloride(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(chǎn)品發(fā)表的科研?獻?Nature.2020Dec;588(7836):169-173.?Nature.2020Jul;583(7817):620-624.3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?Nature.2017Aug24;548(7668):471-475.?Nature.2017Jun15;546(7658):426-430.?NatMethods.2022Mar;19(3):331-340.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,restrictstumourgrowthinpreclini