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蚂蚁淘在线 / 品牌中心 / MCE / Medchemexpress/EPZ-6438(Synonyms: Tazemetostat; E-7438)/HY-13803/200mg

Medchemexpress/EPZ-6438(Synonyms: Tazemetostat; E-7438)/HY-13803/200mg

价格
￥1520.00
货号：HY-13803-10mM*1mLinDMSO
浏览量：127
品牌：MCE
服务
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商品描述
EPZ-6438inhibitstheactivityofhumanPRC2-containingwild-typeEZH2withKiof2.5±0.5nM.

CustomerValidation

  • •NatMed.2017Nov;23(11):1352-1361.
  • •MolOncol.2017Nov11.
  • •Oncotarget.2016Jul19;7(29):46448-46465.
  • •Toxins(Basel).2017May16;9(5).pii:E162.
Description

EPZ-6438inhibitstheactivityofhumanPRC2-containingwild-typeEZH2withKiof2.5±0.5nM.

IC50&Target

Ki:2.5nM(EZH2)[1]

InVitro

EPZ-6438inhibitsEZH2inamannercompetitivewiththesubstrateS-adenosylmethionine(SAM).EPZ-6438inhibitsEZH1,EZH2(inpeptideassay),EZH2(innucleosomeassay)withIC50of392nM,11nMand16nM,respectively.EPZ-6438displaysa35-foldselectivityversusEZH1and>4,500-foldselectivityrelativeto14otherHMTstested[1].

InVivo

EPZ-6438(125mg/kg)inducestumorstasisduringtheadmiNISTrationperiodandproducedasignificanttumorgrowthdelaycomparedwithvehicleafterthedosingperiod.MeasuringEPZ-6438plasmalevelseither5minbeforeor3hafterdosingonday21revealsacleardose-dependentincreaseinsystemicexposure[1].Dose-dependenttargetinhibitionisobservedinPBMCsandbonemarrowfromratsdosedwithEPZ-6438(orallyadministered,100,300,or1,000mg/kg)asmeasuredbyELISA[2].

ClinicalTrial
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References

  • [1].KnutsonSK,etal.DurabletumorregressioningeneticallyalteredmalignantrhaBDoidtumorsbyinhibitionofmethyltransferaseEZH2.ProcNatlAcadSciUSA.2013May7;110(19):7922-7.

    [2].KnutsonSK,etal.SelectiveinhibitionofEZH2byEPZ-6438leadstopotentantitumoractivityinEZH2-mutantnon-Hodgkinlymphoma.MolCancerTher.2014Apr;13(4):842-54.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM1.7460mL8.7300mL17.4599mL
5mM0.3492mL1.7460mL3.4920mL
10mM0.1746mL0.8730mL1.7460mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[1]

EPZ-6438isdissolvedinDMSOandstored,andthendilutedwithappropriatemediabeforeuse[1].

293T(CRL-11268),RD(CRL-136),SJCRH30(CRL-2061),A204(HTB-82),G401(CRL-1441),G402(CRL-1440),KYM-1(JCRB0627),293T,RD,SJCRH30,A204,G401,andG402cellsareused.Onday0,cellsareeitheruntreated,DMSO-treated,ortreatedwithEPZ-6438startingat10µManddecreasingineitherthreefoldorfourfolddilutions.Platesarereadonday0,day4,andday7usingCellTiterGlo,withcompound/mediabeingreplenishedonday4.Onday7,thesix-wellplatesaretrypsinized,centrifuged,andresUSPendedinfreshmediaforcountingbyVi-Cell.Cellsfromeachtreatmentarereplatedattheoriginaldensityin96-wellplatesintriplicate.Cellsareallowedtoadheretotheplateovernight,andcellsaretreatedasonday0.Ondays7,11,and14,platesarereadusingCellTiterGlo,withcompound/mediabeingreplenishedonday11.Averagesoftriplicatesareusedtoplotproliferationoverthetimecourse,andcalculateIC50values.Forcellcycleandapoptosis,G401andRDcellsareplatedin15-cmdishesinduplicateatadensityof1×106cellsperplate.CellsareincubatedwithEPZ-6438at1µM,inatotalof25mL,overacourseof14d,withcellsbeingsplitbacktooriginalplatingdensityonday4,7,and11.CellcycleanalysisandTUNELassayareperformedusingaGuavaflowcytometer[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[1][2]

EPZ-6438ispreparedin0.5%NaCMCplus0.1%Tween80inwater.

Mice[1]
SCIDmicebearings.c.G401xenograftsareinoculateds.c.attherightflankwithG401tumorcells(5×106cellspermouse)in0.2-mLmixtureofbasemediaandMatrigelfortumordevelopment.Thetreatmentsarestartedwhenthetumorsizereached157mm3forthetumorefficacystudy(n=16micepergroup).EPZ-6438(125mg/kg,250mg/kg,and500mg/kg)orvehicle(0.5%NaCMCplus0.1%Tween80inwater)isadministeredorallyBIDatadosevolumeof10µL/gforeither21or28d.Animalbodyweightsaremeasuredeverydayduringthefirstweek,andthentwiceweeklyfortheremainderofthestudy.Tumorsizeismeasuredtwiceweeklyintwodimensionsusingacaliper,andthevolumeisexpressedincubicmillimeters.
Rat[2]
MaleandfemaleSprague-Dawleyrats(8weeksold)areorallytreatedwithEPZ-6438(100,300,or1,000mg/kg)orvehiclefor28daysonceaday.Onday22,thefemalesfromthehighestdosegroupreceivedanotherdoseandaresubsequentlyeuthanizedonday23approximately29hoursafterthelastdose.Allotheranimalsareeuthanizedonday29approximately29hoursafterthelastdoseadministeredonday28.Ateuthanasia,thefullbloodvolumeiscollected,peripheralbloodmononuclearcells(PBMC)areisolated,andcellpelletsarefrozenandstoredat−80°Cbeforeanalysis.A2-mm-thicksliceofskinisformalin-fixedfor24hoursandtransferredto70%ethanol.Thefixedtissuesareparaffinembedded.Bonemarrowsamplesarecollectedfromfemur,tibia,andhipbones,frozenandstoredat−80°Cbeforeanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].KnutsonSK,etal.DurabletumorregressioningeneticallyalteredmalignantrhabdoidtumorsbyinhibitionofmethyltransferaseEZH2.ProcNatlAcadSciUSA.2013May7;110(19):7922-7.

    [2].KnutsonSK,etal.SelectiveinhibitionofEZH2byEPZ-6438leadstopotentantitumoractivityinEZH2-mutantnon-Hodgkinlymphoma.MolCancerTher.2014Apr;13(4):842-54.

MolecularWeight

572.74

Formula

C₃₄H₄₄N₄O₄

CASNo.

1403254-99-8

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:5.0mg/mL(needultrasonic)

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

Purity:99.63%