脫氫表雄酮作用機制 - Medchemexpress - MCE中國

ProductDataSheetDHEACat.No.:HY-14650CASNo.:53-43-0分?式:C??H??O?分?量:288.42作?靶點:AndrogenReceptor;EndogenousMetabolite作?通路:Others;MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗Ethanol:50mg/mL(173.36mM;Needultrasonic)DMSO:50mg/mL(173.36mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)SolventMass1mg5mg10mgConcentration制備儲備液1mM3.4672mL17.3358mL34.6717mL5mM0.6934mL3.4672mL6.9343mL10mM0.3467mL1.7336mL3.4672mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶1.請依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(8.67mM);Clearsolution此?案可獲得≥2.5mg/mL(8.67mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述體系中加?

50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。2.請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.67mM);ClearsolutionPage1of2www.MedChemE此?案可獲得≥2.5mg/mL(8.67mM，飽和度未知)的澄溶液。

以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶液中，混合均勻。3.請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.5mg/mL(8.67mM);Clearsolution此?案可獲得≥2.5mg/mL(8.67mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL??油中，混合均勻。4.請依序添加每種溶劑：10%EtOH90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.67mM);Clearsolution此?案可獲得≥2.5mg/mL(8.67mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄EtOH儲備液加到900μL20%的SBE-β-CD?理鹽??溶液中，混合均勻。5.請依序添加每種溶劑：10%EtOH90%cornoilSolubility:≥2.5mg/mL(8.67mM);Clearsolution此?案可獲得≥2.5mg/mL(8.67mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。以1mL?作液為例，取100μL25.0mg/mL的澄EtOH儲備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性DHEA(Prasterone)最豐富的類醇激素之?。DHEA通過多種信號傳導(dǎo)途徑介導(dǎo)其作?，并通過轉(zhuǎn)化成雄激素和雌

激素衍?物（例如，雄激素，雌激素，7α和7βDHEA(Prasterone)，以及7α和7β表雄甾酮衍?物）通過其特異性受體

起作?。IC??&TargetHumanEndogenousMetabolite體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻?Aging(AlbanyNY).2020May14;12.?ToxicolApplPharmacol.2019Jun5:114612.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].AnagnostopoulouV,etal.Differentialeffectsofdehydro