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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/GSK126(Synonyms: EZH2 inhibitor; GSK2816126A)/HY-13470/100mg
商品详细Medchemexpress/GSK126(Synonyms: EZH2 inhibitor; GSK2816126A)/HY-13470/100mg
Medchemexpress/GSK126(Synonyms: EZH2 inhibitor; GSK2816126A)/HY-13470/100mg
Medchemexpress/GSK126(Synonyms: EZH2 inhibitor; GSK2816126A)/HY-13470/100mg
商品编号： HY-13470-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥1660.00
美元价： 996.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
电话号码： 4000-520-616
电子邮箱： info@ebiomall.com
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商品介绍
GSK126isapotent,highlyselectiveinhibitorofEZH2methyltransferaseactivitywithIC50of9.9nM.

CustomerValidation

  • •Oncotarget.2015Sep29;6(29):27023-36.
  • •Neoplasia.2016Feb;18(2):121-32.
  • •JBiolChem.2016Oct28;291(44):22881-22893.
  • •FEBSJ.2017May;284(9):1309-1323.
Description

GSK126isapotent,highlyselectiveinhibitorofEZH2methyltransferaseactivitywithIC50of9.9nM.

IC50&Target

IC50:9.9nM(EZH2)[1]

InVitro

GSK126potentlyinhibitsbothwild-typeandmutantEZH2methyltransferaseactivitywithsimilarpotencies(Ki=0.5-3nM)independentofsubstrateused,andiscompetitivewithS-adenosyl-methionine(SAM)andnon-competitivewithpeptidesubstrates.GSK126ishighlyselectiveagainstothermethyltransferasesandmultipleotherproteinclasses(EZH1,IC50=680nM)[1].TreatmentofthreeSCLCcelllineswithGSK126,inducesgrowthinhibition.SCLCcelllines(Lu130,H209,andDMS53)aretreatedwith0.5,2,and8μMGSK126,andgrowthcurveisanalyzedbyWST-8assay.InhibitionofcellulargrowthbyGSK126treatmentisobservedat8μMinallthethreecelllines,whileLu130andH209aremoresensitivetoGSK126,evenatlowerdoses[2].

InVivo

GSK126isadmiNISTeredintraperitoneallyatadosevolumeof0.2mLper20gbodyweightinfemalebeigeSCIDmice.GSK126effectivelyinhibitstheproliferationofEZH2mutantDLBCLcelllinesandmarkedlyinhibitsthegrowthofEZH2mutantDLBCLxenograftsinmice[1].

References

  • [1].McCabeMT,etal.EZH2inhibitionasatherapeuticstrategyforlymphomawithEZH2-activatingmutations.Nature.2012Dec6;492(7427):108-12.

    [2].SatoT,etal.PRC2overexpressionandPRC2-targetgenerepressionrelatingtopoorerprognosisinsmallcelllungcancer.SciRep.2013May29;3:1911.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM1.8987mL9.4936mL18.9872mL
5mM0.3797mL1.8987mL3.7974mL
10mM0.1899mL0.9494mL1.8987mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[1]

Thefive-memberPRC2complex(Flag-EZH2,EED,SUZ12,AEBP2,RbAp48)containingeitherwild-typeormutant(A677G,Y641N,Y641C,Y641H,Y641SorY641F)EZH2isprepared.GSK126isdissolvedinDMSOandtestedatconcentrationsof0.6nMto300nMwithafinalDMSOconcentrationof2.5%.Incontrasttowild-typeEZH2whichprefersH3K27me0asasubstrateinvitro,EZH2Y641mutantspreferH3K27me2andhavelittleactivitywithH3K27me0orH3K27me1.TheA677Gmutantisdistinctfromboththewild-typeandY641mutantformsofEZH2inthatitefficientlymethylatesH3K27me0,H3K27me1,andH3K27me2;therefore,histoneH3peptides(residues21-44;10μMfinal)witheitherK27me0(wildtype,A677GEZH2),K27me1(A677GEZH2),orK27me2(A677G,Y641N,Y641C,Y641H,Y641SandY641FEZH2)areusedasmethyltransferasesubstrates.GSK126isaddedtoplatesfollowedbyadditionof6nMEZH2complexandpeptide.AsthepotencyofGSK126isatornearthetightbindinglimitofanassayrunat[SAM]=Km,IC50valuesaremeasuredatahighconcentrationofthecompetitivesubstrateSAMrelativetoitsKm(7.5μMSAMwheretheSAMKmis0.3μM)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[2]

GSK126isdissolvedinDMSO(10mM)andstored,andthendilutedwithappropriatemediabeforeuse[2].

JUB-andPTRF-introducedDMS53cellsareseededatdensityof1×103cells/wellin96-wellplate,andcellulargrowthisanalyzedusingWST-8kitat12,36,60,and84h.CellulargrowthofLu130,H209,andDMS53withtreatmentbyDZNeporGSK126isalsoanalyzedusingWST-8kit.DZNepisdissolvedinPBSat5mM,andcellsareculturedatthefinalconcentrationof5μM.GSK126isdissolvedinDMSOat10mM,andcellsareculturedat0.5,2,and8μM[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[1]

GSK126isdissolvedin20%captisoladjustedtopH4-4.5with1Naceticacid[1].

Mice[1]
GSK126orvehicleisadministeredintraperitoneallyatadosevolumeof0.2mLper20gbodyweight.PfeifferorKARPAS-422cells(1×107)in100%MatrigelareimplantedsubcutaneouslyinfemalebeigeSCIDmice.Tumorsaremeasuredwithcalipers,andblockrandomizedaccordingtotumoursizeintotreatmentgroups.Forefficacystudies,10micearerandomizedineachtreatmentgroupbeforetheinitiationofdosingandGSK126treatmentisinitiatedoncethetumourvolumesareapproximately200mm3inthePfeifferandKARPAS-422studiesand500mm3intheKARPAS-422intermittentdosingstudy.Miceareweighedandtumorsmeasuredwithcaliperstwiceweekly.Two-tailedt-testsareconductedassumingtwosamplesofequalvariance.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].McCabeMT,etal.EZH2inhibitionasatherapeuticstrategyforlymphomawithEZH2-activatingmutations.Nature.2012Dec6;492(7427):108-12.

    [2].SatoT,etal.PRC2overexpressionandPRC2-targetgenerepressionrelatingtopoorerprognosisinsmallcelllungcancer.SciRep.2013May29;3:1911.

MolecularWeight

526.67

Formula

C₃₁H₃₈N₆O₂

CASNo.

1346574-57-9

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

10mMinDMSO

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

Purity:99.32%