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商品详细Medchemexpress/GSK583/HY-100339/50mg

Medchemexpress/GSK583/HY-100339/50mg

商品编号： HY-100339-10mM*1mLinDMSO

品牌： MedChemExp

市场价： ¥2940.00

美元价： 1764.00

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

GSK583isahighlypotentandselectiveinhibitorofRIP2Kinase,withIC₅₀of5nM.

CustomerValidation

•JImmunol.2017May1;198(9):3729-3736.

Description	GSK583isahighlypotentandselectiveinhibitorofRIP2Kinase,withIC₅₀of5nM.
IC₅₀&Target	IC50:5nM(RIP2K)^[1]
InVitro	GSK583(1μM)exhibitsexcellentselectivityinapanelof300kinases,includingp38αandVEGFR2.GSK583potentlyanddosedependentlyinhibitsMDP-stimulatedtumornecrosisfactor-alpha(TNFα)productionwithanIC₅₀of8nM.GSK583demonstratesonlyamodestreductioninpotencywhenprofiledinasimilarMDP-inducedTNFαproductionassayinhumanwholeblood(IC₅₀=237nM)andratwholeblood(IC₅₀=133nM)^[1].
InVivo	GSK583(0.1,1,and10mg/kg,p.o.)inhibitsserumKC(therodentorthologueofIL-8)levelsinratsinadose-dependentmanner,withanIC₅₀derivedfromratbloodconcentrationsof50nM(or20ng/mL).Similarly,GSK583inhibitsserumKClevelsandrecruitmentofneutrophilsintotheperitonealcavityinmiceinadose-dependentmanner,withanIC₅₀of37nM(15ng/mL)derivedfrommousebloodconcentration^[1].
References	[1].HailePAetal.TheIdentificationandPharmacologicalCharacterizationof6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine(GSK583),aHighlyPotentandSelectiveInhibitorofRIP2Kinase.JMedChem,2016May26,59(10):4867-80.

PreparingStockSolutions

ConcentrationVolumeMass	1mg	5mg	10mg

1mM	2.5097mL	12.5486mL	25.0972mL
5mM	0.5019mL	2.5097mL	5.0195mL
10mM	0.2510mL	1.2549mL	2.5097mL

Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.

KinaseAssay
^[1]

AfluorescentpolarizationbasedbindingassayisdevelopedtoquantitateinteractionofnoveltestcompoundsattheATPbindingpocketofRIP2KbycompetitionwithafluorescentlylabeledATPcompetitiveligand.FulllengthFLAGHistaggedRIP2KispurifiedfromabaculovirusexpressionsystemandisusedatafinalassayconcentrationoftwicetheKDapparent.AfluorescentlabeledligandthatisreversIBLeandcompetitivewiththeinhibitorsisusedatafinalassayconcentrationof5nM.Boththeenzymeandligandarepreparedinsolutionsin50mMHEPESpH7.5,150mMNaCl,10mMMgCl₂,1mMDTT,and1mMCHAPS.Testcompoundsarepreparedin100%DMSO,and100nLisdispensedtoindividualwellsofamultiwellplate.Next,5μLofRIP2Kisaddedtothetestcompoundsattwicethefinalassayconcentrationandincubatedatroomtemperaturefor10min.Followingtheincubation,5μLofthefluorescentlabeledligandsolutionisaddedtoeachreactionattwicethefinalassayconcentrationandincubatedatroomtemperatureforatleast10min.Finally,samplesarereadonaninstrumentcapableofmeasuringfluorescentpolarization.Testcompoundinhibitionisexpressedaspercent(%)inhibitionofinternalassaycontrols.Forconcentrationresponseexperiments,normalizeddataarefitusingthefollowingfourparameterlogisticequation:y=A+((B-C))/(1+(10x)/(10C)D),whereyisthe%activity(%inhibition)ataspecifiedcompoundconcentration,Aistheminimum%activity,Bisthemaximum%activity,C=log10(IC₅₀),D=Hillslope,x=log10(compoundconcentration[M]),andpIC₅₀=(−C).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
^[1]

Mice^[1]
FemaleC57Bl/6mice(forcytokineanalyses)ormaleBalb/cmice(forperitonealneutrophilanalyses)(n=10/treatmentgroup)aredosedorally15minpriortoMDPchallengewithvehicleorGSK583(0.1,1,or10mg/kg).Forperitonealneutrophilanalysis,micearesacrificedat4hpost-MDPchallenge(30μg,i.p.)andperitonealfluidiscollectedbylavage.PeritonealneutrophilsarequantifiedbyFACSanalysis.
Rat^[1]
FemaleCrl:CD(SD)rats(n=8/treatmentgroup)aredosedorallywithvehicleorGSK58315minpriortoMDPchallenge(150μg/rat,IV).At2hpostMDPchallenge,ratsaresacrificedandterminalserumispreparedfrombloodcollectedviacardiacstick.Serumcytokinelevels(IL-6,IL-8orKC,IL-1β,andTNFα)arequantifiedbytheMSDplatform.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

[1].HailePAetal.TheIdentificationandPharmacologicalCharacterizationof6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine(GSK583),aHighlyPotentandSelectiveInhibitorofRIP2Kinase.JMedChem,2016May26,59(10):4867-80.

MolecularWeight

398.45

Formula

C₂₀H₁₉FN₄O₂S

CASNo.

1346547-00-9

Storage

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

Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥37mg/mL

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

Purity:98.07%

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