4000-520-616
欢迎来到免疫在线!(蚂蚁淘生物旗下平台)  请登录 |  免费注册 |  询价篮
主营:主营:抑制剂、激动剂、API
咨询热线电话
4000-520-616
当前位置: 首页 > 产品中心 > Small_molecule > Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/50mg
商品详细Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/50mg
Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/50mg
Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/50mg
商品编号: HY-15251-10mM*1mLinDMSO
品牌: MedChemExp
市场价: ¥3360.00
美元价: 2016.00
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
商品介绍
ReparixinisapotentinhibitorofbothCXCL8receptorsCXCR1/2,itinhibitsweaklyCXCR2-mediatedcellmigration(IC50=100nM),whereasitstronglyblocksCXCR1-mediatedchemotaxis(IC50=1nM).

CustomerValidation

  • AnnRheumDis.2016Apr;75(4):730-8.
  • NatCommun.2017May26;8:15584.
  • CellDeathDis.2017Jul13;8(7):e2932.
  • StemCells.2015Dec;33(12):3558-68.
  • BiochimBiophysActa.2017Jan;1863(1):220-230.
  • Oncotarget.2017Jul21;8(36):60210-60222.
  • Oncogenesis.2016Jun13;5(6):e234.
  • JGastroenterolHepatol.2017May8.
  • VetImmunolImmunopathol.2016Dec;182:52-58.
Description

ReparixinisapotentinhibitorofbothCXCL8receptorsCXCR1/2,itinhibitsweaklyCXCR2-mediatedcellmigration(IC50=100nM),whereasitstronglyblocksCXCR1-mediatedchemotaxis(IC50=1nM).

IC50&Target

IC50:5.6/80nM(CXCR1wt/CXCR1Ile43Val,inL1.2cell)[1]

InVitro

ReparixinisapotentfunctionalinhibitorofCXCL8-inducedBIOLOGicalactivitiesonhumanPMNswithamarkedselectivity(around400-fold)forCXCR1,asshowninspecificexperimentsonCXCR1/L1.2andCXCR2/L1.2transfectedcellsandonhumanPMNs.TheefficacyofReparixinissignificantlylowerinL1.2cellsexpressingIle43ValCXCR1mutant(IC50valuesof5.6nMand80nMforCXCR1wtandCXCR1Ile43Val,respectively)[1].Reparixinisanon-competitiveallostericinhibitorofIL-8receptorswitha400-foldhigherefficacyininhibitingCXCR1activitythanCXCR2[2].

InVivo

ReparixinisaninhibitorofCXCL8receptorCXCR1andCXCR2activation,hasbeenshowntoattenuateinflammatoryresponsesinvariousinjurymodels.Spontaneouslyhypertensiverats(SHR)areadmiNISTeredasubcutaneousinjectionofReparixin(5mg/kg)dailyfor3weeks.Reparixineffectivelydecreasessystolicbloodpressureandincreasedthebloodflow[3].ReparixinreducesthelevelsofIL-1βinthebrainaftermiddlecerebralarteryocclusion/reperfusion(MCAo)inmice.BarsrepresentlevelsofIL-1β(pg/100mg)measuredbyELISAinthebraintissuesofmicesubjectedornot(SHAM)toMCAoandpretreatedwithvehicleorReparixin(30mg/kg,s.c.)[4].

References
  • [1].MoriconiA,etal.Designofnoncompetitiveinterleukin-8inhibitorsactingonCXCR1andCXCR2.JMedChem.2007Aug23;50(17):3984-4002.

    [2].BertiniR,etal.ReceptorbindingmodeandpharmacologicalcharacterizationofapotentandselectivedualCXCR1/CXCR2non-competitiveallostericinhibitor.BrJPharmacol.2012Jan;165(2):436-54.

    [3].KimHY,etal.Reparixin,aninhibitorofCXCR1andCXCR2receptoractivation,attenuatesbloodpressureandhypertension-relatedmediatorsexpressioninspontaneouslyhypertensiverats.BiolPharmBull.2011;34(1):120-7.

    [4].SousaLF,etal.BlockadeofCXCR1/2chemokinereceptorsprotectsagainstbraindamageinischemicstrokeinmice.Clinics(SaoPaulo).2013;68(3):391-4.

    [5].KrishnamurthyA,etal.Identificationofanovelchemokine-dependentmolecularmechanismunderlyingrheumatoidarthritis-associatedautoantibody-mediatedboneloss.AnnRheumDis.2016Apr;75(4):721-9.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM3.5287mL17.6435mL35.2871mL
5mM0.7057mL3.5287mL7.0574mL
10mM0.3529mL1.7644mL3.5287mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[1]

Reparixinisdissolvedinsalineattheappropriatedilution[1].

L1.2CellsUSPension(1.5-3×106cells/mL)isincubatedat37°Cfor15mininthepresenceofvehicleorofReparixin(1nM-1μM)andnextseededintriplicatesintheuppercompartmentofthechemotacticchamber.Differentagonistsareseededinthelowercompartmentofthechamberatthefollowingconcentrations:1nMCXCL8,0.03nMfMLP,10nMCXCL1,2.5nMCCL2,30nMC5a.Thechemotacticchamberisincubatedat37°Cinairwith5%CO2for45min(humanPMNs)or2h(monocytes).Attheendofincubation,thefilterisremoved,fixed,andstainedandfiveoilimmersionfieldsathighmagnification(100×)arecountedforeachmigrationwellaftersamplecoding.L1.2migrationisevaluatedusing5μmporesizeTranswellfilters[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[3][4]

Reparixinisdissolvedinsalineandadministeredsubcutaneously(MiceandRat).

Rat[3]
TheReparixin-treatedgroupcontained5SHR(SHR-R),whereequalnumbersofnormalsaline-treatedSHR(SHR-N)andWKY(WKY-N)servedascontrols.Eighteen-week-oldSHRreceivedasubcutaneousinjectionofReparixin(5mg/kg)onceperdayfor3weeks.Reparixineffectsonbloodflow,bloodpressureandbodyweightaremeasuredbeforetreatmentandthenweeklyuntil1weekafterthefinalinjection.TheeffectofReparixinontheexpressionofhypertension-relatedmediatorsinthoracicaortas,aswellasnitricoxide(NO)plasmalevels,isexamined1weekafterthefinalinjection.Attheendofthe4weekperiod,bothcontrolandReparixin-treatedratsareanesthetizedviaintraperitonealinjectionofthiopental(50mg/kg),andbloodandtissuesamplesarecollected.
Mice[4]
C57BL/6Jmice(8-10weeksold/20-25g)areused.ThesubcutaneousadministrationofReparixin(30mg/kg)isperformed60minutesbeforecerebralischemiainduction.Theanimalsaredividedintothefollowingthreeexperimentalgroups:Sham(i.e.,thegroupinwhichthearteriesarevisualized,butthereisnoocclusionofthemiddlecerebralartery),Vehicle(i.e.,thegrouppre-treatedwiththevehicle,phosphatebuffersolution,60minutesbeforeMCAo)andReparixin(i.e.,thegrouppre-treatedwiththedrug60minutesbeforeMCAo).ToevaluateneurologicalsignssecondarytoMCAo,theanimalsareassessedwiththeSHIRPAbattery24hafterreperfusion.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References
  • [1].MoriconiA,etal.Designofnoncompetitiveinterleukin-8inhibitorsactingonCXCR1andCXCR2.JMedChem.2007Aug23;50(17):3984-4002.

    [2].BertiniR,etal.ReceptorbindingmodeandpharmacologicalcharacterizationofapotentandselectivedualCXCR1/CXCR2non-competitiveallostericinhibitor.BrJPharmacol.2012Jan;165(2):436-54.

    [3].KimHY,etal.Reparixin,aninhibitorofCXCR1andCXCR2receptoractivation,attenuatesbloodpressureandhypertension-relatedmediatorsexpressioninspontaneouslyhypertensiverats.BiolPharmBull.2011;34(1):120-7.

    [4].SousaLF,etal.BlockadeofCXCR1/2chemokinereceptorsprotectsagainstbraindamageinischemicstrokeinmice.Clinics(SaoPaulo).2013;68(3):391-4.

    [5].KrishnamurthyA,etal.Identificationofanovelchemokine-dependentmolecularmechanismunderlyingrheumatoidarthritis-associatedautoantibody-mediatedboneloss.AnnRheumDis.2016Apr;75(4):721-9.

MolecularWeight

283.39

Formula

C₁₄H₂₁NO₃S

CASNo.

266359-83-5

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥500mg/mL

Reparixinisprepareinvehicle(sterilesaline)[5].

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

References
  • [1].MoriconiA,etal.Designofnoncompetitiveinterleukin-8inhibitorsactingonCXCR1andCXCR2.JMedChem.2007Aug23;50(17):3984-4002.

    [2].BertiniR,etal.ReceptorbindingmodeandpharmacologicalcharacterizationofapotentandselectivedualCXCR1/CXCR2non-competitiveallostericinhibitor.BrJPharmacol.2012Jan;165(2):436-54.

    [3].KimHY,etal.Reparixin,aninhibitorofCXCR1andCXCR2receptoractivation,attenuatesbloodpressureandhypertension-relatedmediatorsexpressioninspontaneouslyhypertensiverats.BiolPharmBull.2011;34(1):120-7.

    [4].SousaLF,etal.BlockadeofCXCR1/2chemokinereceptorsprotectsagainstbraindamageinischemicstrokeinmice.Clinics(SaoPaulo).2013;68(3):391-4.

    [5].KrishnamurthyA,etal.Identificationofanovelchemokine-dependentmolecularmechanismunderlyingrheumatoidarthritis-associatedautoantibody-mediatedboneloss.AnnRheumDis.2016Apr;75(4):721-9.

Purity:99.88%ee.:100.00%