Carfilzomib-PR-171-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECarfilzomibCat.No.:HY-10455CASNo.:868540-17-4Synonyms:PR-171分⼦式:C₄₀H₅₇N₅O₇分⼦量:719.91作⽤靶点:Proteasome;Autophagy;Apoptosis作⽤通路:MetabolicEnzyme/Protease;Autophagy;Apoptosis储存⽅式:Powder-20°C3years4°C2years*该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤。溶解性数据体外实验DMF:≥100mg/mL(138.91mM)DMSO:50mg/mL(69.45mM;Needultrasonic)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.3891mL6.9453mL13.8906mL5mM0.2778mL1.3891mL2.7781mL10mM0.1389mL0.6945mL1.3891mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤.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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:2.5mg/mL(3.47mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.47mM);Clearsolution3.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.5mg/mL(3.47mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Carfilzomib(PR-171)不可逆的蛋⽩酶体(proteasome)抑制剂，其在ANBL-6和RPMI8226细胞中的IC50为5nM。IC50&TargetIC50:5nM(Proteasome)体外研究CarfilzomibdisplayspreferentialinvitroinhibitorypotencyagainsttheChT-Lactivityintheβ5subunit,withover80%inhibitionatdosesof10nMandaboveandlittleornoeffectonthePGPHandT-Lactivitiesatdosesupto100nM.CarfilzomibdecreasestheviabilityofANBL-6,RPMI8226cells,U266andKAS-6/1cellswithanIC50lessthan5nM.CarfilzomibovercomeDexresistance,inthatMM1.RcellsrevealsanIC50of15.2nM,lessthanthevalueof29.3nMforparentalMM1.Scells[1].Co-treatmentwithcarfilzomibandHDACIsleadstosynergisticinductionofcelldeathinvariousmantlecelllymphomalinesandprimarymantlecelllymphomacells.CombinedtreatmentwithcarfilzomiborONX0912withvorinostatinHF-4BandGrantacellssharplyincreasescaspaseactivation,PARPcleavage,JNKactivation,MnSOD2induction,andDNAdamage[2].体内研究Carfilzomib(2.0mg/kg,i.v.)inconbinationwith70mg/kgvorinostatvirtuallyabrogatestumorgrowthinGranta-luciferacecellxenograftflankmodel.Combinedtreatmentresultsinapronouncedreductioninbioluminescencecomparedtoanimalstreatedwithsingleagentsorcontrolswithminimaltoxicity[2].PROTOCOLCellAssay[1]WST-1isusedtodeterminetheeffectsofproteasomeinhibitorsoncellproliferationaccordingtothemanufacturer'sprotocol.TheinhibitionofproliferationiscalculatedinrelationtoparallelcontrolcellsthatreceivevehiclealoneandtabulatedinKaleidaGraph3.0.1orExcel2000.Alinearsplinefunctionisusedtointerpolatethemedianinhibitoryconcentration(IC50)usingXLfit4software.Thedegreeofresistance(DOR)iscalculatedusingtheformula:DOR=IC50(resistantcells)/IC50(sensitivecells).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAnimalstudiesareperformedutilizingBeige-nude-XIDmice.10×106Granta514cellsarepelleted,washedAdministration[2]twicewith1XPBS,injectedsubcutaneouslyintotherightflank.Oncethetumorsarevisible,5to6micearetreatedwithcarfilzomib±vorinostatandprogressoftumorgrowthorregressionismonitored.StockvorinostatandcarfilzomibisdissolvedinDMSOand10%sulfobutyletherbetacyclodextrinin10mMcitratebufferpHrespectively.Theyarestoredin−80°Cinsmallaliquotsanddilutedbeforeinjection.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•NatCommun.2020Sep4;11(1):4417.•Biomaterials.16September2022.•CellChemBiol.2020Dec31;S2451-9456(20)30513-4.•Elife.2019Mar25;8:e45457.•JMedChem.2021Dec29.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].KuhnDJ,etal.Potentactivityofcarfilzomib,anovel,irreversibleinhibitoroftheubiquitin-proteasomepathway,againstpreclinicalmodelsofmultiplemyeloma.Blood.2007Nov1;110(9):3281-90.[2].DasmahapatraG,etal.Carfilzomibinteractssynergisticallywithhistonedeacetylaseinhibitorsinmantlecelllymphomacellsinvitroandinvivo.MolCancerTher.2011Se