4-Hydroxytamoxifen-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemE4-HydroxytamoxifenCat.No.:HY-16950CASNo.:68047-06-3分⼦式:C₂₆H₂₉NO₂分⼦量:387.51作⽤靶点:EstrogenReceptor/ERR作⽤通路:Others储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥28mg/mL(72.26mM)扫描⼆维码，H2O:<0.1mg/mL(insoluble)运⽤溶解⽅案计算器*"≥"meanssoluble,butsaturationunknown.获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5806mL12.9029mL25.8058mL5mM0.5161mL2.5806mL5.1612mL10mM0.2581mL1.2903mL2.5806mL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，并请注意储备液的保存⽅式和期限。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:≥2.08mg/mL(5.37mM);Clearsolution此⽅案可获得≥2.08mg/mL(5.37mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL20.8mg/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。1/4www.MedChemEwww.MedChemE2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(5.37mM);Suspendedsolution;Needultrasonic此⽅案可获得2.08mg/mL(5.37mM)的均匀悬浊液，悬浊液可⽤于⼝服和腹腔注射。以1mL⼯作液为例，取100μL20.8mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶3.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.08mg/mL(5.37mM);Clearsolution此⽅案可获得≥2.08mg/mL(5.37mM，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100μL20.8mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性4-Hydroxytamoxifen⼀种选择性的雌激素受体调节剂(SERM)。IC50&TargetEstrogenreceptorCRISPR/Cas93.3nM(IC50)体外研究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].体内研究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.户使⽤本产品发表的科研⽂献•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