Dutasteride-13C-15N-d-GG-745-sup-13-sup-C-sup-15-sup-N-d-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDutasteride-13C,15N,dCat.No.:HY-13613S2Synonyms:GG745-13C,15N,d;GI198745-13C,15N,d分⼦式:C₂₆₁₃CH₂₉DF₆N₁₅NO₂分⼦量:531.52作⽤靶点:5alphaReductase;Apoptosis;Isotope-LabeledCompounds作⽤通路:MetabolicEnzyme/Protease;Apoptosis;Others储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Dutasteride-13C,15N,d15N和氘代标记的Dutasteride(HY-13613)。Dutasteride(GG745)5α还原酶同⼯酶(5α-reductaseisozymes)抑制剂，还可能因其结构域DHT相似对雄激素受体(AR)产⽣脱靶效应。体外研究Stableheavyisotopesofhydrogen,carbon,andotherelementshavebeenincorporatedintodrugmolecules,largelyastracersforquantitationduringthedrugdevelopmentprocess.Deuterationhasgainedattentionbecauseofitspotentialtoaffectthepharmacokineticandmetabolicprofilesofdrugs[1].Dutasterideinhibits3H-Tconversionto3H-DHTand,asanticipated,inhibitsT-inducedsecretionofPSAandproliferation.HoweverthedrugalsoinhibitedDHT-inducedPSAsecretionandcellproliferation(IC50approximately1μM)[2].DutasteridecompetesforbindingtheLNCaPcellARwithanIC50approximately1.5μM.Highconcentrationsofdutasteride(10-50μM),butnotfinasteride,insteroid-freemedium,resultedinenhancedcelldeath,possiblybyapoptosis[2].Dutasteridereducescellviabilityandcellproliferationinbothcelllinestested(androgen-responsive(LNCaP)andandrogen-unresponsive(DU145)humanprostatecancer(PCa))[3].体内研究GG745hasaterminalhalf-lifeofapproximately240hr,andsingledosesof>10mgdecreasedDHTlevelssignificantlymorethandidsingle5-mgdosesoffinasteride[4].Inplacebotreatedmenwithoutprostatecancertherewasan8.3%medianincreaseinPSAatmonth24comparedwith-59.5%inthosewhoreceiveddutasteride,usingdoubledvaluestocorrectfordutasteridetreatment[5].Toxicity:Dutasteridemayaffectmalefertilityandsteroidhormonedynamics.Therefore,a21-dayreproductionstudywasconductedtodeterminetheeffectsofdutasteride(10,32and100μg/L)onfishreproduction.Exposuretodutasteridesignificantlyreducedfecundityoffishandaffectedseveralaspectsofreproductiveendocrinefunctionsinbothmalesandfemales[6].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].LazierCB,etal.Dutasteride,thedual5alpha-reductaseinhibitor,inhibitsandrogenactionandpromotescelldeathintheLNCaPprostatecancercellline.Prostate.2004Feb1;58(2):130-44.[2].BiancolellaM,etal.Effectsofdutasterideontheexpressionofgenesrelatedtoandrogenmetabolismandrelatedpathwayinhumanprostatecancercelllines.InvestNewDrugs.2007Oct;25(5):491-7.[3].BramsonHN,etal.UniquepreclinicalcharacteristicsofGG745,apotentdualinhibitorof5AR.JPharmacolExpTher.1997Sep;282(3):1496-502.[4].AndrioleGL,etal.Clinicalusefulnessofserumprostatespecificantigenforthedetectionofprostatecancerispreservedinmenreceivingthedual5alpha-reductaseinhibitordutasteride.JUrol.2006May;175(5):1657-62.[5].Margiotta-CasaluciL,etal.Modeofactionofhumanpharmaceuticalsinfish:theeffectsofthe5-alpha-reductaseinhibitor,dutasteride,onreproductionasacasestudy.AquatToxicol.2013Mar15;128-129:113-23.[6].RussakEM,etal.ImpactofDeuteriumSubstitutiononthePharmacokineticsofPharmaceuticals.AnnPharmacother.2019Feb;53(2):211-216.McePdfHeightCaution:Producthasnot