Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEElacestrantCat.No.:HY-19822CASNo.:722533-56-4Synonyms:RAD1901分?式:C??H??N?O?分?量:458.63作?靶點(diǎn):EstrogenReceptor/ERR作?通路:Others儲存?式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:160mg/mL(348.87mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1804mL10.9020mL21.8041mL5mM0.4361mL2.1804mL4.3608mL10mM0.2180mL1.0902mL2.1804mL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(sealedstorage,awayfrommoistureandlight)。-80°C儲存時，請?jiān)?個?內(nèi)使?，-20°C儲存時，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)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(shí)驗(yàn)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(shí)驗(yàn)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%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥4mg/mL(8.72mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥4mg/mL(8.72mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥4mg/mL(8.72mM);ClearsolutionBIOLOGICALACTIVITY?物活性Elacestrant(RAD1901)?種具有?服活性的的選擇性雌激素受體(ER)降解劑(SERD)，對ERα和ERβ的IC50值分別為48和870nM。IC50&TargetIC50:48nM(ERα),870nM(ERβ)[1]體外研究RAD1901selectivelybindstoanddegradestheERandisapotentantagonistofER-positivebreastcancercellproliferation.RAD1901treatmentexhibitsdose-dependentinhibitionofERαexpression,withanEC50of0.6nM.TreatmentofER-positiveMCF-7cellswithE2resultsinapotentanddose-dependentincreaseinproliferation,withanEC50of4pM.TreatmentofcellswithRAD1901inthepresenceof10pME2resultsinadose-dependentdecreaseinproliferation,withanIC50valueof4.2nM[1].體內(nèi)研究RAD1901producesarobustandprofoundinhibitionoftumorgrowthinMCF-7xenograftmodels.RAD1901-treatedanimalssurvivedlongerthanthosetreatedwitheithercontrolorfulvestrant.RAD1901preservesovariectomy-inducedbonelossandpreventestheuterotropiceffectsofE2[1].PROTOCOLKinaseAssay[1]RAD1901isseriallydilutedinES2screeningbuffertoconcentrationsrangingfrom10to10-6μM.Aliquots(25μL)ofeachdilutionareaddedtoablack384-wellmicrotiterplate,intriplicate.TheER–Fluormonecomplexispreparedasdirected,with2nMFluormoneES2and30nMER.A25μLaliquotofthispreparationisaddedtoeachreactionwell.Theplatesaresealedandincubatedinthedarkatroomtemperaturefor4h.Polarizationvaluesforeachwellaremeasuredandplottedagainsttheconcentrationofthetestcompound.TheIC50isdeterminedfromatleastthreeindependentexperiments,withE2servingasapositivecontrol[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]Forproliferationassays,MCF-7cellsaretreatedwith2%charcoal-strippedFBS–MEMcontaining10pME2witheitherRAD1901oradditionalE2atconcentrationsrangingfrom10-9to1M.Themediumisremovedafter48hofincubationandthecellsarelysedbyadding100μlofCellTiterGlo.Theplatesaregentlymixedonaplateshakerfor10minbeforetheluminescentsignalismeasuredonaluminometer.TheEC50andIC50ofthetestcompoundarethendefined[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:RAD1901isstoredasadrypowder,formulatedforuseasahomogenoussuspensionin0.5%(w/v)Administration[1]methylcelluloseindeionizedwater.Fourteendaysaftertumorcellimplantation,themicearerandomizedinto2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEninegroupsof15animalseachandtreatedwithvehicle,tamoxifen(1mg/animaleveryotherday),fulvestrant(0.5mg/animaldaily),orRAD1901(0.3,1,3,10,30,60,90,and120mg/kgdaily).Tumorvolumesareevaluatedtwiceperweek[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JMedChem.2020Oct8;63(19):11085-11099.?MolCancerTher.2020Jul;19(7):1395-1405.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GarnerF,etal.RAD1901:anovel,orallybioavailableselectiveestrogenreceptordegraderthatdemonstratesantitumoractivityinbreastcancerxenograftmodels.AnticancerDrugs.201