R547-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemER547Cat.No.:HY-10014CASNo.:741713-40-6分⼦式:C₁₈H₂₁F₂N₅O₄S分⼦量:441.45作⽤靶点:CDK;GSK-3;Apoptosis作⽤通路:CellCycle/DNADamage;PI3K/Akt/mTOR;StemCell/Wnt;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.66mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.66mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性R547⼀种⾼效、选择性的，⼝服有效的ATP竞争性的CDK抑制剂，对CDK1/cyclinB、CDK2/cyclinE和CDK4/cyclinD1作⽤的Ki值分别为2nM、3nM、1nM[1][2][3][4][5]。IC50&TargetCdk1/cyclinBCDK2/cyclinECDK4/cyclinDcdk2/cyclinA2nM(Ki)3nM(Ki)1nM(Ki)0.1nM(IC50)CDK2/cyclinECdk1/cyclinBCDK3/CyclinECDK5/p351/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE0.4nM(IC50)0.2nM(IC50)0.8nM(IC50)0.1nM(IC50)cdk6/cyclinD3CDK7/cyclinHGSK-3αGSK-3β4nM(IC50)171nM(IC50)46nM(IC50)260nM(IC50)体外研究R547effectivelyinhibitsCDK1/cyclinB,CDK2/cyclinE,andCDK4/cyclinD1(Ki=1–3nmol/L)andisinactive(Ki>5,000nmol/L)againstapanelof>120unrelatedkinasesincell-freeassays[4].R547effectivelyinhibitstheproliferationoftumorcelllinesindependentofmultidrugresistantstatus,histologictype,retinoblastomaprotein,orp53status,withIC50s[4].R547reducesphosphorylationofthecellularretinoblastomaproteinatspecificCDKphosphorylationsitesatthesameconcentrationsthatinducedcellcyclearrest[4].R547hasanti-proliferativeactivityintumorcellsindependentofp53,retinoblastoma,orMDRstatus[4].R547blockstumorcellsinG1plusG2andinducesapoptosis[4].R547inducesapoptosisasmeasuredbyDNAfragmentation[4].R547inhibitsphosphorylationofretinoblastomaproteininhumantumorcells[4].CellCytotoxicityAssay[4]CellLine:Humantumorcelllines(MDA-MB-468,MDA-MB-435,MCF-7,HCT116,SW480,RKO,HT-29,HCT15,H460a,C33A,DU145,OSA-CL,LOX,JEKO-1,REC-1)Concentration:MTTassayIncubationTime:5daysResult:Haspotentinvitroantiproliferativeactivity.CellCycleAnalysis[4]CellLine:R547,HCT116Concentration:0.1μM,0.2μM,0.6μMIncubationTime:20hoursResult:DecreaseinBrdUrdincorporationandinpercentageSphaseinadose-dependent,indicativeofacellcycleblockinG1-SplusG2-M.WesternBlotAnalysis[4]CellLine:HCT116cellsConcentration:0.1μM,0.2μM,0.6μMIncubationTime:24hours,48hours,72hoursResult:Showedabandcorrespondingtoap48/retinoblastomafragmentthatbecomesmoreintenseat48and72hours.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究R547hassignificantinvivoefficacywithdailyoralandonceweeklyi.v.dosing[4].R547inhibitsphosphorylationofretinoblastomaproteinintumors[4].AnimalModel:13-14weeksoldfemaleimmunodeficientnudemice(23-25g),withHCT116/H460a/MDA-MB-435/DU145/LOX/A549cellsxenograft[4]Dosage:40mg/kgAdministration:Oraladministration;daily;for3-weeksResult:Showedantitumoractivityinallofthemodelsinthisstudy.户使⽤本产品发表的科研⽂献•Science.2017Dec1;358(6367):eaan4368.•CellChemBiol.2018Feb15;25(2):135-142.e5.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ChuXJ,DePintoW,BartkovitzD,SoSS,VuBT,PackmanK,LukacsC,DingQ,JiangN,WangK,GoelzerP,YinX,SmithMA,HigginsBX,ChenY,XiangQ,MoliterniJ,KaplanG,GravesB,LoveyA,FotouhiN.Discoveryof[4-Amino-2-(1-methanesulfonylpiperidin-4[2].BayésM,RabassedaX,ProusJR.Gatewaystoclinicaltrials.MethodsFindExpClinPharmacol.2007Jul-Aug;29(6):427-37.[3].MartinF,ThomsonTM,SewerA,DrubinDA,MathisC,WeisenseeD,PrattD,HoengJ,PeitschMC.Assessmentofnetworkperturbationamplitudesbyapplyinghigh-throughputdatatocausalbiologicalnetworks.BMCSystBiol.2012May31;6:54.[4].DePinto,WandaetalInvitroandinvivoactivityofR547:apotentandselectivecyclin-dependentkinaseinhibitorcurrentlyinphaseIclinicaltrialsMolecularCancerTherapeutics(2006),5(11),2644-2658[5].Jones,CliffordD.;Andrews,DavidM.Imidazolepyrimidineamidesaspotent,orallybioavailablecyclin-dependentkinaseinhibitorsBioorganic&MedicinalChemistryLetters(2008),