Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemER547Cat.No.:HY-10014CASNo.:741713-40-6分?式:C??H??F?N?O?S分?量:441.45作?靶點(diǎn):CDK;GSK-3;Apoptosis作?通路:CellCycle/DNADamage;PI3K/Akt/mTOR;StemCell/Wnt;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.66mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.66mM);ClearsolutionBIOLOGICALACTIVITY?物活性R547?種?效、選擇性的，?服有效的ATP競(jìng)爭(zhēng)性的CDK抑制劑，對(duì)CDK1/cyclinB、CDK2/cyclinE和CDK4/cyclinD1作?的Ki值分別為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?邊的抑制劑?師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)體外研究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?邊的抑制劑?師www.MedChemE體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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),