Medchemexpress/MLN4924(Synonyms: Pevonedistat)/HY-70062/5mg,MCE,,MCE,MedChemExp,MedChemExpress,+,,Array.Array.Array蚂蚁淘厂家直采.

产品名称：Medchemexpress/MLN4924(Synonyms: Pevonedistat)/HY-70062/5mg

产品编号：HY-70062-10mM*1mLinDMSO

市场价：¥2340.00

场地：美国(厂家直采)

产品分类：生化试剂>生物分子>小分子>

联系QQ：1570468124

电话号码：4000-520-616

邮箱： info@ebiomall.com

美元价：$117.00

品牌： MCE

公司：Medchemexpress

公司分类：

商品介绍

MLN4924isapotentandselectiveNEDD8-activatingenzyme(NAE)inhibitorwithIC₅₀of4.7nM.

CustomerValidation

•NatCommun.2017May22;8:15398.
•Elife.2016Apr11;5.pii:e14087.
•Oncotarget.2017Sep23;8(49):86395-86409.
•Oncotarget.2016Oct4;7(40):66087-66099.
•Oncotarget.2016Jun14;7(24):35643-35654.
•AmJPhysiolLungCellMolPhysiol.2017Jul1;313(1):L104-L114.

•Virology.2015Mar;477:10-7.
•AnnHematol.2014Sep;93(9):1499-508.
•BiochemBiophysResCommun.2017Jan29;483(1):223-229.
•TechnolCancerResTreat.2016Aug;15(4):527-34.
•UlmUniversity.13-01-2017.

Description

MLN4924isapotentandselectiveNEDD8-activatingenzyme(NAE)inhibitorwithIC₅₀of4.7nM.

IC₅₀&Target

IC50:4.7nM(NAE)^[1]

InVitro

MLN4924isapotentinhibitorofNAE,andisselectiverelativetothecloselyrelatedenzymesUAE,SAE,UBA6andATG7(IC₅₀=1.5,8.2,1.8and>10μM,respectively)whenevaluatedinpurifiedenzymeassaysthatmonitortheformationofE2-UBLthioesterreactionproducts.MLN4924selectivelyinhibitsNAEactivitycomparedtothecloselyrelatedubiquitin-activatingenzyme(UAE,alsoknownasUBA1)andSUMO-activatingenzyme(SAE;aheterodimerofSAE1andUBA2subunits),inpurifiedenzymeandcellularassays.MLN4924exhibitspotentcytotoxicactivityagainstavarietyofhumantumour-derivedcelllines^[1].

InVivo

MLN4924(sc,10mg/kg,30mg/kg,or60mg/kg)inhibitstheNEDD8pathwayresultinginDNAdamageinMicebearingHCT-116xenografts^[1].Pevonedistat(sc,120mg/kg)andTNF-α(10μg/kg)synergisticallycauseliverdamageinSDrats^[2].

ClinicalTrial

ViewMoreCollapse

References

[1].SoucyTA,etal.AninhibitorofNEDD8-activatingenzymeasanewapproachtotreatcancer.Nature.2009Apr9;458(7239):732-6.
[2].FSWolenski,etal.TheNAEinhibitorpevonedistat(MLN4924)synergizeswithTNF-αtoactivateapoptosis.CellDeathDiscovery1,Articlenumber:15034(2015)

PreparingStockSolutions

ConcentrationVolumeMass	1mg	5mg	10mg

1mM	2.2547mL	11.2734mL	22.5469mL
5mM	0.4509mL	2.2547mL	4.5094mL
10mM	0.2255mL	1.1273mL	2.2547mL

Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.

CellAssay
^[1]

MLN4924isdissolvedinDMSOandstored,andthendilutedwithappropriatemediumbeforeuse^[1].

HCT-116cellsgrownin6-wellcell-culturedishesaretreatedwith0.1%DMSO(control)or0.3μMMLN4924for24h.Wholecellextractsarepreparedandanalysedbyimmunoblotting.ForanalysisoftheE2-UBLthioesterlevels,lysatesarefractionatedbynon-reducingSDS-PAGEandimmunoblottedwithpolyclonalantibodiestoUbc12,Ubc9andUbc10.Foranalysisofotherproteins,lysatesarefractionatedbyreducingSDS-PAGEandprobedwithprimaryantibodiesasfollows:mousemonoclonalantibodiestoCDT1,p27,geminin,ubiquitin,securin/PTTGandp53orrabbitpolyclonalantibodiestoNRF2,CyclinB1andGADD34^[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
^[1]^[2]

MLN4924isdissolvedinDMSOandthendilutedwithPBSorsaline.

Mice^[1]
MicebearingHCT-116tumoursof300-500mm³areadministeredasingleMLN4924dose(of10,30or60mg/kg),andtumorsareexcisedatvarioustime-pointsoverthesubsequent24hperiod.TherelativelevelsofNEDD8-cullinandNRF2areestimatedbyquantitativeimmunoblotanalysisusingAlexa680-labelledanti-IgGasthesecondaryantibody.ThestatisticaldifferencebetweenthegroupsforNEDD8-cullininhibitionisdeterminedusingtheKruskal-Wallistest.FortheanalysisofCDT1andphosphorylatedCHK1(Ser317)levelsintumoursections,formalin-fixed,paraffin-embeddedtumoursectionsarestainedwiththerelevantantibodies,amplifiedwithHRP-labelledsecondaryantibodiesanddetectedwiththeChromoMapDABKit.Slidesarecounterstainedwithhaematoxylin.ImagesarecapturedusinganEclipseE800microscopeandRetigaEXicolourdigitalcameraandprocessedusingMetamorphsoftware.CDT1andphosphorylatedCHK1levelsareexpressedasafunctionoftheDABsignalarea.
Rat^[2]
Ten-week-oldmaleSprague-Dawleyratsareused.Acrosstwostudies,atotalofeightanimalsineachgrouparedosedwithvehicle,TNF-α,MLN4924,orMLN4924+TNF-α.Animalsarefirstintravenouslyadministeredeithervehicle(1×PBS)or10μg/kgTNF-α.Onehourlater,theyaresubcutaneouslyadministeredvehicle(20%sulfobutyletherbeta-cyclodextrinin50mMcitratebuffer,pH3.3)or120mg/kgMLN4924.Scheduledeuthanasiaoccurred24hpostdose.Unscheduledeuthanasiaisperformedwhenanimalsexhibitedmoribundconditions.SerumiscollectedatnecropsyandanalyzedbyIdexxLaboratoriesforserumchemistryMarkersofliverdamage.Additionally,theliversfromfiveanimalsineachgroupareremoved,separatedintotwosectionsandeitherfrozenat-80°Cforsubsequentproteinanalysisorfixedin10%neutralbufferedformalin,embeddedinparaffin,sectionedat4-6μm,mountedonglassslides,stainedwithhematoxylinandeosin,andanalyzedwithanOlympusBX51lightmicroscopeforhistopathologyassessment.Microscopicfindingsarerecordedinconcordancewiththestandardizednomenclatureforclassifyinglesionswithintheliversofrats.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

[1].SoucyTA,etal.AninhibitorofNEDD8-activatingenzymeasanewapproachtotreatcancer.Nature.2009Apr9;458(7239):732-6.
[2].FSWolenski,etal.TheNAEinhibitorpevonedistat(MLN4924)synergizeswithTNF-αtoactivateapoptosis.CellDeathDiscovery1,Articlenumber:15034(2015)

MolecularWeight

443.52

Formula

C₂₁H₂₅N₅O₄S

CASNo.

905579-51-3

Storage

Powder	-20°C	3years
	4°C	2years
Insolvent	-80°C	6months
	-20°C	1month

Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥111.25mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:98.00%

SelectBatch: