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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/GKT137831/HY-12298/50mg
商品详细Medchemexpress/GKT137831/HY-12298/50mg
Medchemexpress/GKT137831/HY-12298/50mg
Medchemexpress/GKT137831/HY-12298/50mg
商品编号： HY-12298-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥2380.00
美元价： 1428.00
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
GKT137831isanovel,specificdualNADPHoxidase(NOX1/4)inhibitor.GKT137831haspotencybothonhumanNox4(Ki=140±40nM)andhumanNox1(Ki=110±30nM)andisfound15-foldlesspotentonNox2(Ki=1750±700nM)and3-foldlesspotentonNox5(Ki=410±100nM).

CustomerValidation

  • •MolCellEndocrinol.2016Dec5;437:268-279.
  • •ArchBiochemBiophys.2017Feb15;616:1-12.
  • •BiomedPharmacother.2016Dec6;86:32-40.
Description

GKT137831isanovel,specificdualNADPHoxidase(NOX1/4)inhibitor.GKT137831haspotencybothonhumanNox4(Ki=140±40nM)andhumanNox1(Ki=110±30nM)andisfound15-foldlesspotentonNox2(Ki=1750±700nM)and3-foldlesspotentonNox5(Ki=410±100nM).

IC50&Target

Ki:140±40nM(Nox4),110±30nM(Nox1)[1]

InVitro

GKT137831isapotentNox4inhibitor(Ki=120±30nM)withanaffinitysimilartotheirreversIBLeandunspecificflavoproteininhibitorDiphenyliodonium(DPI;Ki=70±10nM)[1].AdmiNISTrationofGKT137831throughoutthe72-hourperiodofnormoxiaorhypoxiaexposureattenuatesHPASMCproliferationundernormoxicconditionsatthe20μMconcentrationbuthadnoeffectonproliferationinnormoxicHPAECs.InthepreventionparADIgm,GKT137831attenuateshypoxia-inducedHPASMCandHPAECproliferationat5and20μM.ComplementaryassaysofcellproliferationmeasuringtheexpressionofPCNAormanualcellcountingconfirmedthatGKT137831attenuateshypoxia-inducedpulmonaryvascularcellproliferation[2].

InVivo

DuringthelasthalfofCCl4injections,somemicearetreatedwithGKT137831daily.CCl4-inducedliverfibrosisismorepronouncedinSOD1mucomparedtoWTmice.LiverfibrosisinbothSOD1muandWTmiceisattenuatedbyGKT137831treatment.Theincreasedhepaticα-SMAexpressionismarkedlydecreasedinSOD1mumicetreatedwithGKT137831,toalevelsimilartothatofWTmicegiventheNOX1/4inhibitor[1].

ClinicalTrial
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References

  • [1].AoyamaT,etal.Nicotinamideadeninedinucleotidephosphateoxidaseinexperimentalliverfibrosis:GKT137831asanovelpotentialtherapeuticagent.Hepatology.2012Dec;56(6):2316-27.

    [2].GreenDE,etal.TheNox4inhibitorGKT137831attenuateshypoxia-inducedpulmonaryvascularcellproliferation.AmJRespirCellMolBiol.2012Nov;47(5):718-26.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.5326mL12.6630mL25.3261mL
5mM0.5065mL2.5326mL5.0652mL
10mM0.2533mL1.2663mL2.5326mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[2]

GKT137831isdissolvedinDMSOandstored,andthendilutedwithappropriatemedia(DMSO1%)beforeuse[2].

MonolayersofHPAECsandHPASMCsarepropagatedincultureandplacedinnormoxic(21%O2,5%CO2)orhypoxic(1%O2,5%CO2)conditionsfor72hours.GKT137831(0.1-20μM),orvehicle(1%DMSO)areaddedtotheculturemediumattheonset(preventionregimen)orduringthelast24hours(interventionregimen)ofa72-hourhypoxiaexposureregimen[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[1]

GKT137831ispreparedincornoil[1].

Mice[1]
Specificpathogen-free,wild-type(WT)C57BL/6Jmiceareused.Forthecarbontetrachloride(CCl4)modelofliverfibrosis,6weekoldmalemiceareinjectedintraperitoneallywithCCl4,whichisdiluted1:3incornoil,orwithvehicle(cornoil)atadoseof0.5μL/gofbodyweighttwiceaweekforatotalof12injections.DuringthelasthalfofCCl4treatment,micearetreatedwith60mg/kgoftheNOX1/4inhibitorGKT137831orvehiclebyintragastricinjectiondaily.Micearesacrificed48hoursafterthelastCCl4injection.Forthebileductligation(BDL)model,6weekoldmalemiceareanesthetized.Afterlaparotomy,thecommonbileductisligatedtwiceandtheabdomenclosed.TheshamoperationisperformedsimilarlywithoutBDL.From11daysafteroperation,micearetreatedwith60mg/kgoftheNOX1/4inhibitorGKT137831orvehiclebydailyintragastriclavage.Micearesacrificed21daysafteroperation.Serumlevelsofalanineaminotransferase(ALT)aremeasuredwithacommercialkit.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].AoyamaT,etal.Nicotinamideadeninedinucleotidephosphateoxidaseinexperimentalliverfibrosis:GKT137831asanovelpotentialtherapeuticagent.Hepatology.2012Dec;56(6):2316-27.

    [2].GreenDE,etal.TheNox4inhibitorGKT137831attenuateshypoxia-inducedpulmonaryvascularcellproliferation.AmJRespirCellMolBiol.2012Nov;47(5):718-26.

MolecularWeight

394.85

Formula

C₂₁H₁₉ClN₄O₂

CASNo.

1218942-37-0

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥37mg/mL

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

Purity:99.43%