脱氢表雄酮作用机制 - Medchemexpress - MCE中国

ProductDataSheetDHEACat.No.:HY-14650CASNo.:53-43-0分⼦式:C₁₉H₂₈O₂分⼦量:288.42作⽤靶点:AndrogenReceptor;EndogenousMetabolite作⽤通路:Others;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验Ethanol:50mg/mL(173.36mM;Needultrasonic)DMSO:50mg/mL(173.36mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)SolventMass1mg5mg10mgConcentration制备储备液1mM3.4672mL17.3358mL34.6717mL5mM0.6934mL3.4672mL6.9343mL10mM0.3467mL1.7336mL3.4672mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶1.请依序添加每种溶剂：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(8.67mM);Clearsolution此⽅案可获得≥2.5mg/mL(8.67mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊

50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.67mM);ClearsolutionPage1of2www.MedChemE此⽅案可获得≥2.5mg/mL(8.67mM，饱和度未知)的澄溶液。

以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶液中，混合均匀。3.请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.5mg/mL(8.67mM);Clearsolution此⽅案可获得≥2.5mg/mL(8.67mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。4.请依序添加每种溶剂：10%EtOH90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.67mM);Clearsolution此⽅案可获得≥2.5mg/mL(8.67mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄EtOH储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶液中，混合均匀。5.请依序添加每种溶剂：10%EtOH90%cornoilSolubility:≥2.5mg/mL(8.67mM);Clearsolution此⽅案可获得≥2.5mg/mL(8.67mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL25.0mg/mL的澄EtOH储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性DHEA(Prasterone)最丰富的类醇激素之⼀。DHEA通过多种信号传导途径介导其作⽤，并通过转化成雄激素和雌

激素衍⽣物（例如，雄激素，雌激素，7α和7βDHEA(Prasterone)，以及7α和7β表雄甾酮衍⽣物）通过其特异性受体

起作⽤。IC₅₀&TargetHumanEndogenousMetabolite体外研究DHEA(Prasterone)isaneffectiveantiapoptoticfactor,reversingtheserumdeprivation-inducedapoptosisinprostatecancercells(DU145andLNCaPcelllines)aswellasincoloncancercells(Caco2cellline).DHEA(Prasterone)significantlyreducesserumdeprivation-inducedapoptosisinall3cancercelltypes,quantitatedwiththeAPOPercentageassay(apoptosisisreducedfrom0.587±0.053to0.142±0.0016or0.059±0.002aftertreatmentfor12hourswithDHEAorNGF,respectively;n=3,P<0.01),andbyflowcytometryanalysis(FACS)forDU145cells.TheantiapoptoticeffectofDHEAisdosedependentwithanEC50atnanomolarconcentrations(EC50:11.2±3.6nMand12.4±2.2nMinDU145andCaco2cells,respectively)[1].DHEA(Prasterone)istheprincipalsexsteroidprecursorinhumansandcanbeconverteddirectlytoandrogens.DHEA(Prasterone)(≥1μM)causesadose-dependentinhibitionofChub-S7proliferation,asassessedbythymidineincorporationassays.DHEA(Prasterone)treatmentinhibitsexpressionofthekeyglucocorticoid-regulatinggenesH6PDH(≥100nM)andHSD11B1(≥1μM)indifferentiatingpreadipocytesinadose-dependentmanner.Inkeepingwiththisfinding,DHEA(Prasterone)treatment(≥1μM)resultsinamarkedreductionin11β-HSD1oxoreductaseactivity(≥1μM)andaconcurrentincreaseindehydrogenaseactivityatthehighestDHEAdoseused(25μMDHEA)indifferentiatedadipocytes[2].体内研究DHEA(Prasterone)inthediet(0.45%w/w)ofmaleB6mice(groupsoffivemice)treatedfor8weeksledtosignificantdecreasesinbodytemperaturecomparedwithmicefedthecontrolAIN-76Adiet.Asimilarcomparisonindicatedthatcontrolandpair-fedmicearealsosignificantlydifferent.AnimalsfedDHEA(Prasterone)havesignificantlylowertemperaturesthanmicefedthecontroldiet26/29timestested;micepairfedtothoseontheDHEA(Prasterone)dietarelessaffected,with8/29valuessignificantlylowerthaninmicefedAIN-76Aadlibitum.ThetemperaturesofmicefedDHEA(Prasterone)orpairfedtoDHEA(Prasterone)aresignificantlydifferent21/29timestested.BodyweightsaresignificantlygreaterinmicefedthecontroldietthaninmicefedDHEAorpairfedtoDHEA(Prasterone).Foodintake(gramsperday)fromcagesareaveragedforeachweek(n=7),exceptforWeek9(n=3).TheamountoffoodPage2of3www.MedChemEintakeissignificantlydecreasedinmicefedDHEA(Prasterone).Bydesign,micepairfedtoDHEA(Prasterone)ate

aboutthesameamount.Thus,itappearsthatDHEA(Prasterone)reducesbodytemperaturebyfoodrestrictionand

byaseparatemechanism[3].PROTOCOLCellAssay[2]Chub-S7preadipocytesandhumanprimarypreadipocytesareseededintoa24-wellplateatdensities1×105and2.5×105respectively.Followingovernightculture,mediumissupplementedwithDHEA,androstenediol,orDHEA(Prasterone)(0-100μM).Following24-,48-,or72hincubation,cellproliferationisassessedbyincubationwithradiolabeledthymidine(0.2μCi/well)forthefinal6hofculture.ProteinsareprecipitatedwithTCA,andcellsarescrapedinNaOH.Therespectivecontentofradiolabelednuclearmaterialintheresultinglysatesisanalyzedbyscintillationcounting[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]MicearefedPurinaLabChowuntilthestartofexperiments(Day0).GroupsoffivemicearethenfedpelletedAIN-76AdietcontainingeithernoadditiveorDHEA(0.45%w/w)between0900and1000hr.Dietsarestoredat4°Cfornolongerthansixmonthstomaintainoptimalactivity.Micearegiventhedietsadlibitum,exceptformicethatarepairfedtomicetreatedwithDHEA(Prasterone).TheamountsofAIN-76Adietthepair-fedmicereceivedaredeterminedbytheweightoffoodconsumedbytheDHEA-fedmiceonadailybasis.Bodyweights(grams)aremeasuredatdifferenttimepointsstartingatDay1andendingatDay59.Dailyfoodintakes(gramsperday)aredeterminedbyweighingthefoodconsumedpercageoffivemice.Themean±SEMvaluesarecalculatedforweeks1to8(n=7);week9hadonly3days.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Aging(AlbanyNY).2020May14;12.•ToxicolApplPharmacol.2019Jun5:114612.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].AnagnostopoulouV,etal.Differentialeffectsofdehydro