5-Aminosalicylic-acid-d3-disodium-Mesalamine-d-sub-3-sub-disodium-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemE5-Aminosalicylicacid-d3disodiumCat.No.:HY-15027S3Synonyms:Mesalamine-d3disodium;5-ASA-d3disodium;Mesalazine-d3disodium分子式:C₇H₂D₃NNa₂O₃分子量:200.12作用靶点:PPAR;NF-κB;EndogenousMetabolite;PAK;Isotope-LabeledCompounds作用通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;VitaminDRelated/NuclearReceptor;NF-κB;Cytoskeleton;Others储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性5-Aminosalicylicacid-d3disodium是氘代标记的5-AminosalicylicAcid(HY-15027)。5-Aminosalicylicacid(Mesalamine)是一种特异性的PPARγ激动剂，还抑制p21-激活激酶1(PAK1)和NF-κB。5-Aminosalicylicacid可抑制骨桥蛋白(OPN)的活性。体外研究Stableheavyisotopesofhydrogen,carbon,andotherelementshavebeenincorporatedintodrugmolecules,largelyastracersforquantitationduringthedrugdevelopmentprocess.Deuterationhasgainedattentionbecauseofitspotentialtoaffectthepharmacokineticandmetabolicprofilesofdrugs[1].5-Aminosalicylicacid(5-ASA)isaspecificagonistforPPARγ,andonlyPPARγbutnotPPARαorPPARδinducesp65degradation.5-Aminosalicylicacidinducesdegradationofp65proteinindicativeofPPARγ'sE3ubiquitinligaseactivity.5-AminosalicylicacidalsoinhibitsPAK1atthemRNAlevelwhichissuggestiveofanadditionalmechanismindependentofPPARγligandactivation.5-AminosalicylicacidblocksNF-κBinintestinalepithelialcells(IECs)throughinhibitionofPAK1[2].Pretreatmentwith5-Aminosalicylicacid(5-ASA)orNimesulideatdifferentconcentration(10-1000μmol/L)for12-96h,inhibitsthegrowthofHT-29coloncarcinomacellsinadoseandtime-dependentmanner.However,thesuppressionof5-AminosalicylicacidorNimesulidehasnostatisticalsignificance.ThegrowthofHT-29coloncarcinomacellsisinhibiteddose-dependentlywhenpretreatedwithdifferentdosesofcombined5-AminosalicylicacidandNimesulide.Combined5-Aminosalicylicacid(finalconcentration100μM)andNimesulide(finalconcentration10-1000μM)inhibitstheproliferationofHT-29coloncarcinomacellsinadose-dependentmanner,beingmorepotentthancorrespondingdoseofNimesulide.Similarly,combinedNimesulide(finalconcentration100μM)and5-Aminosalicylicacid(finalconcentration10-1000μM)alsoinhibitstheproliferationofthesecellsdose-1/2 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEdependently,beingmorepotentthancorrespondingdoseof5-Aminosalicylicacid[3].体内研究5-Aminosalicylicacid(5-ASA)hasanantineoplasticeffectinaxenografttumormodel.Toevaluatetheinvivoantineoplasiceffectof5-Aminosalicylicacid,SCIDmiceengraftedwithHT-29coloncancercellsaretreateddailyfor21consecutivedayswith5-Aminosalicylicacidat50mM.Attheendofthetreatment,areductionof80-86%oftumorweightandvolumeisobservedinSCIDmicereceiving5-AminosalicylicacidcomparedwithcontrolmiceormicetreatedwithGW9662alone.Theantineoplasticeffectof5-Aminosalicylicacidisalreadydetectableafter10daysof5-Aminosalicylicacidtreatment.Similarresultsareobtainedwithmicetreatedwith5-Aminosalicylicacidat5mM.Antitumorigeniceffectof5-Aminosalicylicacidiscompletelyabolishedat21daysbysimultaneousintraperitonealadministrationofGW9662.Thus,theobservedantineoplasticeffectof5-AminosalicylicacidisatleastpartiallydependentonPPARγ[4].REFERENCESDammannK,etal.PAK1modulatesaPPARγ/NF-κBcascadeinintestinalinflammation.BiochimBiophysActa.2015Oct;1853(10PtA):2349-60.RamadanA,etal.Mesalazine,anosteopontininhibitor:Thepotentialprophylacticandremedialrolesininducedliverfibrosisinrats.ChemBiolInteract.2018Jun1;289:109-118.FangHM,etal.5-aminosalicylicacidincombinationwithNimesulideinhibitsproliferationofcoloncarcinomacellsinvitro.WorldJGastroenterol.2007May28;13(20):2872-7.RousseauxC,etal.The5-aminosalicylicacidantineoplasticeffectintheintestineismediatedbyPPARγ.Carcinogenesis.2013Nov;34(11):2580-6.RussakEM,etal.ImpactofDeuteriumSubstitutiononthePharmacokineticsofPharmaceuticals.AnnPharmacother.2019Feb;53(2):211-21