Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECarfilzomibCat.No.:HY-10455CASNo.:868540-17-4Synonyms:PR-171分?式:C??H??N?O?分?量:719.91作?靶點(diǎn):Proteasome;Autophagy;Apoptosis作?通路:MetabolicEnzyme/Protease;Autophagy;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2years*該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?。溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMF:≥100mg/mL(138.91mM)DMSO:50mg/mL(69.45mM;Needultrasonic)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.3891mL6.9453mL13.8906mL5mM0.2778mL1.3891mL2.7781mL10mM0.1389mL0.6945mL1.3891mL請(qǐng)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(chǔ)備液；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?.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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:2.5mg/mL(3.47mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.47mM);Clearsolution3.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.5mg/mL(3.47mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Carfilzomib(PR-171)不可逆的蛋?酶體(proteasome)抑制劑，其在ANBL-6和RPMI8226細(xì)胞中的IC50為5nM。IC50&TargetIC50:5nM(Proteasome)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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