Ixazomib-citrate-MLN9708-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIxazomibcitrateCat.No.:HY-10452CASNo.:1239908-20-3Synonyms:MLN9708分?式:C??H??BCl?N?O?分?量:517.12作?靶點:Proteasome;Autophagy作?通路:MetabolicEnzyme/Protease;Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:250mg/mL(483.45mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.9338mL9.6689mL19.3379mL5mM0.3868mL1.9338mL3.8676mL10mM0.1934mL0.9669mL1.9338mL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。-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?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，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(4.02mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.02mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.02mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ixazomibcitrate(MLN9708)20S蛋?酶體胰凝乳蛋?酶樣蛋??解β5位點的可逆抑制劑，IC50為3.4nM和Ki為0.93nM。IC50&TargetIC50:3.4nM(20Sproteasomeβ5),31nM(20Sproteasomeβ1),3500nM(20Sproteasomeβ2)[3]體外研究Ixazomibcitrate(MLN9708;0.20-3.20μM)inhibitsthecellgrowthofbothcelllineseffectivelyinatime-anddose-dependentmanner.IxazomibinducescellcyclearrestinMG-63andSaos-2cells.Ixazomibinducesapoptosismainlythroughthecaspasespathwayandrequirestheactivationofbothcaspase8andcaspase9.Ixazomibtreatmentincreasesthelevelsofpro-apoptoticproteinsanddownregulatestheanti-apoptoticproteinsthatcontrolMOMP.IxazomibtreatmentinducesthereleaseofCytc,Smac,OMIfrommitochondriaanddecreasestheproteinlevelsofXIAP.IxazomibinhibitstheinvasionabilityofMG-63andSaos-2cellsanddecreasesboththeexpressionandsecretionlevelsofMMP2/9[1].Ixazomibcitrate(MLN9708;12nM)showsinhibitoryactivityagainstC-LandT-Lproteasomeactivities.TreatmentofH929andMM.1SMMcellswithIxazomibtriggersamarkedincreaseinproteolyticcleavageofpoly(ADP)ribosepolymerase(PARP),asignatureeventduringapoptosis.Ixazomibinducescleavageofcaspase-3,anupstreamactivatorofPARP.IxazomibinduceseIf2-αkinaseactivityandproteinlevelsofBipandCHOP/GADD153.IxazomibblocksBMSCs-inducedMMcellproliferation,inhibitsinvitrocapillarytubuleformation,andtargetNF-κB[2].體內(nèi)研究Ixazomibcitrate(MLN9708;11mg/kg)significantlyinhibitsMMtumorgrowthandprolongssurvivalinthehumanplasmacytomaMM.1Sxenograftmousemodel.ThebloodchemistryprofilesofIxazomib-treatedmiceshownormallevelsofcreatinine,hemoglobin,andbilirubin.Ixazomibdramaticallyincreasesthenumberofcleaved-caspase-3positivecellsofthexenograftmodel[2].PROTOCOLCellAssay[1]CellviabilityisassessedusingtheMTTassay.Cellsaretrypsinizedandseededin96-wellplateat5000cellsperwell.CellsaretreatedwithIxazomiborDMSOinbasalmediumattheindicateddosesandtimes.Cellviabilityisdeterminedrelativetocontrolcellstreatedwithvehiclealone.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalIxazomibisdissolvedin5%2-hydroxypropyl-β-cyclodextrinat2mg/mLconcentration.ThehumanAdministration[2]plasmacytomaxenografttumormodelisusedintheassay.CB-17SCIDmice(n=21)aresubcutaneouslyinoculatedwith5.0×106MM.1Scellsin100μLserum-freeRPMI-1640medium,andrandomizedtotreatmentgroupswhentumorsreach250-300mm3.Micearetreatedwithvehicle,bortezomib(1mg/kg;i.v)or2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIxazomib(11mg/kg;i.v)twiceweeklyfor3weeks.Animalsareeuthanizedwhentheirtumorsreach2cm3.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?CellChemBiol.2021Aug30;S2451-9456(21)00393-7.?JMedChem.2022Jul27.?Patent.US20220054606A1.?ResearchSquarePreprint.2022Feb.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LiuR,etal.ANewPerspectiveforOsteosarcomaTherapy:ProteasomeInhibitionbyMLN9708/2238SuccessfullyInducesApoptosisandCellCycleArrestandAttenuatestheInvasionAbilityofOsteosarcomaCellsinVitro.CellPhysiolBiochem.2017Jan27;41(2[2].ChauhanD,etal.InvitroandinvivoselectiveantitumoractivityofanovelorallybioavailableproteasomeinhibitorMLN9708againstmultiplemyelomacells.ClinCancerRes.2011Aug15;17(16):5311-21.[3].KuppermanE,etal.EvaluationoftheproteasomeinhibitorMLN9708inpreclinicalmodelsofhumancance