ADWX-1-DataSheet-生命科學試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEADWX1Cat.No.:HY-P1409分子式: C???H???N??O??S?分子量: 4071.85Sequence: Val-Gly-Ile-Asn-Val-Lys-Cys-Lys-His-Ser-Arg-Gln-Cys-Leu-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Thr-Asn-Gly-Lys-Cys-His-Cys-Thr-Pro-Lys(Disulfidebonds:Cys7-Cys27,Cys13-Cys32,Cys17-Cys34)SequenceShortening:VGINVKCKHSRQCLKPCKDAGMRFGKCTNGKCHCTPK(Disulfidebonds:Cys7-Cys27,Cys13-Cys32,Cys17-Cys34)作用靶點: PotassiumChannel作用通路: MembraneTransporter/IonChannel儲存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性ADWX1是一種強效靶向抑制Kv1.3的新型肽，IC50值為1.89pM。ADWX1特異性抑制Kv1.3通道活性，并抑制初始鈣信號傳導(dǎo)和NF-κB激活。ADWX1改善大鼠實驗性自身免疫性腦脊髓炎(experimentalautoimmuneencephalomyelitis,EAE)疾病。ADWX1用于研究T細胞介導(dǎo)的自身免疫性疾病。IC50&TargetKv1.3Kv1.11.89pM(IC50)0.65nM(IC50)體外研究ADWX1(1,10nM,1h)inhibitsIL-2andIFN-γproductions,andinhibitshumansCD4+CCR7-TEMcellsactivationselectively[2].ADWX1(1,10nM,50min)reduces[Ca2+]inactivatedCD4+CCR7-TCMcellsfromEAErats[2].ADWX1(1,10nM,1h)reducesNF-κBactivationandsuppressesKv1.3expressionatbothmRNAandproteinlevelspreferentiallyinmyelinbasicprotein(MBP)(HY-P77995)-stimulatedCD4+CCR7-TcellsfromEAErats[2].ADWX1(1,10nM,3days)suppressesTh17activationbutnotdifferentiationinCD4+CCR7-Tcells[2].RT-PCR[2]CellLine:CD4+CCR7-TcellsfromEAErats1/2 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEConcentration:1,10nMIncubationTime:1hResult:SuppressedKv1.3genemRNAexpressionpreferentially.WesternBlotAnalysis[2]CellLine:CD4+CCR7-TcellsfromEAEratsConcentration:1,10nMIncubationTime:1hResult:SuppressedKv1.3proteinexpressionpreferentially.體內(nèi)研究ADWX1(100μg/kg/day,s.c.,3days)amelioratesthediseasethroughtheinhibitionofIL-2andIFN-γproductionsandCCR7-TEMproliferationinexperimentalautoimmuneencephalomyelitis(EAE)ofSprague-Dawleyrats[2].ADWX1(5/10mg/kg,s.c.,2weeks)inducesnopathologicalchangesinthebehaviorortissuesoftherats(acutetoxicityassay)[2].AnimalModel:Stablesymptomsofacuteexperimentalautoimmuneencephalomyelitis(EAE)wereinducedbyimmunizingSprague-Dawleyrats[2].Dosage:100μg/kg/day,3daysAdministration:subcutaneousinjection(s.c.)Result:Reducedneurologicalscorescomparedwithvehicle-treatedratsondays10,11,12,13and14.Reducedininflammatoryinfiltratesanddemyelinationintheaffectedspinalcordsignificantly.InhibitedIL-2andIFN-γproductions.InhibitedtheTcellproliferationtriggeredbyhighandlowconcentrationsofmyelinantigeninadose-dependentmanner.DecreasedCD4+CCR7-TEMcells.REFERENCESHanS,etal.StructuralbasisofapotentpeptideinhibitordesignedforKv1.3channel,atherapeutictargetofautoimmunedisease.JBiolChem.2008Jul4;283(27):19058-65.LiZ,etal.SelectiveinhibitionofCCR7(-)effectormemoryTcellactivationbyanovelpeptidetargetingKv1.3channelinaratexperimentalautoimmuneencephalomyelitismodel.JBiolChem.2012Aug24;287(35):29479-94.McePdfHeight2/2 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECaution:Producthasnotbeenfullyva