4-Hydroxytamoxifen-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemE4-HydroxytamoxifenCat.No.:HY-16950CASNo.:68047-06-3分?式:C??H??NO?分?量:387.51作?靶點:EstrogenReceptor/ERR作?通路:Others儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥28mg/mL(72.26mM)掃描?維碼，H2O:<0.1mg/mL(insoluble)運?溶解?案計算器*"≥"meanssoluble,butsaturationunknown.獲得適合您實驗體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5806mL12.9029mL25.8058mL5mM0.5161mL2.5806mL5.1612mL10mM0.2581mL1.2903mL2.5806mL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，并請注意儲備液的保存?式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?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(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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:≥2.08mg/mL(5.37mM);Clearsolution此?案可獲得≥2.08mg/mL(5.37mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL20.8mg/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。1/4www.MedChemEwww.MedChemE2.請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(5.37mM);Suspendedsolution;Needultrasonic此?案可獲得2.08mg/mL(5.37mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.08mg/mL(5.37mM);Clearsolution此?案可獲得≥2.08mg/mL(5.37mM，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100μL20.8mg/mL的澄DMSO儲備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性4-Hydroxytamoxifen?種選擇性的雌激素受體調(diào)節(jié)劑(SERM)。IC50&TargetEstrogenreceptorCRISPR/Cas93.3nM(IC50)體外研究4-Hydroxytamoxifen(Monohydroxytamoxifen)isaselectiveoestrogenreceptorantagonist,withanIC50of3.3nMforthe[3H]oestradiolbindingtooestrogenreceptor.4-Hydroxytamoxifen(10,100nM)enablestoinhibitthebindingof[3H]oestradioltothehuman8Soestrogenreceptor[1].4-Hydroxytamoxifenactivatesintein-linkedinactiveCas9,reducesoff-targetCRISPR-mediatedgeneediting.Inhumancells,conditionallyactiveCas9smodifytargetgenomicsiteswithupto25-foldhigherspecificitythanwild-typeCas9[2].體內(nèi)研究4-Hydroxytamoxifen(0.2,1and5μg/day,p.o.)causesadose-relateddecreaseinuterinewetweightofimmaturerats[1].4-Hydroxytamoxifen(6μg/0.1mLsesameoil/day,s.c.)effectivelyattenuatesmethamphetamine-inducednigrostriataldopaminedepletionsinbothsexesofintactandgonadectomizedC57BL/6Jmice.4-Hydroxytamoxifendoesnotalterthedopaminecontentlevelsinthestriatum[3].PROTOCOLKinaseAssay[1]Cytosol(200μL)isincubatedfor30minat4°Cwithdifferentconcentrationsofoestradiol,tamoxifenand(4-Hydroxytamoxifen)ordihydroxytamoxifenadministeredin10μLmethanol.Controltubesareincubatedwith10μLmethanolaloneandnon-specificbindingisdeterminedinaparallelincubationofcytosol(200μL)withmethanol(10μL)containingDES(5×106M).[2,4,6,7-3H]Oestradiolsolution(50μL)inTEDbufferisaddedtoeachtubetogiveafinalconcentrationof2×10-9M.Incubationiscontinuedfor4h(4°C)andthen400μLofasuspensionofdextran-coatedcharcoal(250mg%NoritA,2.5mg%dextran)inTEDbufferareaddedandallowedtostandfor20min.Tubesarecentrifugedat800gfor10min(4°C)and400μLsamplesofthesupernatantareaddedto10mLtritiumscintillator(6gbutylPBD,135mLtoluene,720mldioxan,100gnaphthalene,45mLabsolutemethanol).Samplesarecountedfor10mininaliquidscintillationspectrometer.Countingefficiencyisdeterminedbyexternalstandardization(35-36%).Resultsarerepresentedasapercentageofthespecificallyboundradioactivity(c.p.m.)inthecontroltubes[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/4www.MedChemEwww.MedChemEAnimalMice[3]Administration[3]Animalsofeachsexaredividedintotwogroups:onegroupreceives4-Hydroxytamoxifen[6μg/0.1mLsesameoil/day,subcutaneously(s.c.)startingat06.00h]injectionsforthreeconsecutivedays,whiletheothergroupreceivesanequivalentamountofsesameoilinjectionfor3days.Fourhoursfollowingthethirdinjection,eachgroupisthensubdividedintotwogroups:onereceivesfourcumulativedosesofmethamphetaminehydrochloride(10mg/kg,s.c.),andtheotherreceivesacomparablevolumeofsalineat2-hintervals.Bilateralgonadectomyisperformedunderpentobarbitalanesthesia(50mg/kg,intraperitoneally).Fiveweeksaftersurgery,gonadectomizedmiceofeachsexarerandomlydividedintosixgroups.Fivegroupsofeachsexreceivethreedailyinjectionsofvariousconcentrationsof4-Hydroxytamoxifen(0,1.5,3.0,6.0,and12.0μg/0.1mLsesameoil/day).Fourhoursfollowingthethirdinjection,micereceivefourdosesofmethamphetamine(MA,10mg/kg)at2-hintervals.Theremaininggroupofeachsexreceivessesameoilpretreatmentforthreeconsecutivedays,followedbysalineinjections,andservesasthecontrolgroup[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?MolCell.2020Aug6;79(3):425-442.e7.?NatCommun.2018Sep25;9(1):3923.?CellDeathDis.2019Sep20;10(10):700.?CellDeathDis.2019Sep20;10(10):700.?JMolMed(Berl).2019Aug;97(8):1183-1193.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].JordanVC,etal.Amonohydroxylatedmetaboliteoftamoxifenwithpotentantioestrogenicactivity.JEndocrinol.1977Nov;75(2):305-16.[2].DavisK