MedKoo Biosciences/Estramustine phosphate sodium/100310/25mg

Synonym:estramustinePhosphate;USbrandname:Emcyt.Foreignbrandname:Estracyt.Abbreviation:EM.Codenames:Leo299;Ro222296000.

IUPAC/ChemicalName:(8R,9S,13S,14S,17S)-13-methyl-17-(phosphonooxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ylbis(2-chloroethyl)carbamatehydrate

InChiKey:DMFOFEOTRNQDBB-CUGULWCMSA-N

InChiCode:InChI=1S/C23H32Cl2NO6P.H2O/c1-23-9-8-18-17-5-3-16(31-22(27)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)32-33(28,29)30;/h4,5,14,18-21H,2,4,6-13H2,1H3,(H2,28,29,30);1H2/t18-,19-,20+,21+,23+;/m1./s1

SMILESCode:O=C(OC1=CC=C2[C@@]3([H])CC[C@]4(C)[C@@H](OP(O)(O)=O)CC[C@@]4([H])[C@]3([H])CCC2=C1)N(CCCl)CCCl.[H]O[H]

TechnicalData

AdditionalInformation

DRUGDESCRIPTION
Estramustinephosphatesodium,anantineoplasticagent,isanoff-whitepowderreadilysolubleinwater.EMCYTCapsulesarewhiteandopaque,eachcontainingestramustinephosphatesodiumasthedisodiumsaltmonohydrateequivalentto140mgestramustinephosphate,fororaladmiNISTration.Eachcapsulealsocontainsmagnesiumstearate,silicondioxide,sodiumlaurylsulfate,andtalc.Gelatincapsuleshellscontainthefollowingpigment:titaniumdioxide.Chemically,estramustinephosphatesodiumisestra-1,3,5(10)-triene-3,17-diol(17β)-,3­[bis(2-chloroethyl)carbamate]17-(dihydrogenphosphate),disodiumsalt,monohydrate.Itisalsoreferredtoasestradiol3-[bis(2-chloroethyl)carbamate]17-(dihydrogenphosphate),disodiumsalt,monohydrate.EstramustinephosphatesodiumhasanempiricformulaofC23H30Cl2NNa2O6P•H2O,acalculatedmolecularweightof582.4.
 
Estramustinephosphate(Figure1)isamoleculecombiningestradiolandnornitrogenmustardbyacarbamatelink.Themoleculeisphosphorylatedtomakeitwatersoluble.
Estramustinephosphatetakenorallyisreadilydephosphorylatedduringabsorption,andthemajormetabolitesinplasmaareestramustine(Figure2),theestroneanalog(Figure3),estradiol,andestrone.
Prolongedtreatmentwithestramustinephosphateproduceselevatedtotalplasmaconcentrationsofestradiolthatfallwithinrangessimilartotheelevatedestradiollevelsfoundinprostaticcancerpatientsgivenconventionalestradioltherapy.Estrogeniceffects,asdemonstratedbychangesincirculatinglevelsofsteroidsandpituitaryhormones,aresimilarinpatientstreatedwitheitherestramustinephosphateorconventionalestradiol.Themetabolicurinarypatternsoftheestradiolmoietyofestramustinephosphateandestradiolitselfareverysimilar,althoughthemetabolitesderivedfromestramustinephosphateareexcretedataslowerrate.
 
 
 

References

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2:KoieT,OhyamaC,YamamotoH,HatakeyamaS,YoneyamaT,HashimotoY,KamimuraN.Safetyandeffectivenessofneoadjuvantluteinizinghormone-releasinghormoneagonistpluslow-doseestramustinephosphateinhigh-riskprostatecancer:aProspectivesingle-armstudy.ProstateCancerProstaticDis.2012Dec;15(4):397-401.doi:10.1038/pcan.2012.29.Epub2012Aug14.PubMedPMID:22890389.

3:MinatoA,FujimotoN,KuboT,HaradaS,AkasakaS,MatsumotoT.Efficacyofestramustinephosphateaccordingtoriskclassificationofcastration-resistantprostatecancer.MedOncol.2012Dec;29(4):2895-900.doi:10.1007/s12032-012-0178-z.Epub2012Feb10.PubMedPMID:22323054.

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7:HirayamaY,ItoY,KanamaruT,SonodaT,AoyamaM,NakamuraN,KawamuraM.[Acaseofcastration-refractoryprostatecancershowingmarkeddecreaseofserumPSAlevelafterzoledronicacidtreatmentwithestramustinephosphateandprednisolone].GanToKagakuRyoho.2011Mar;38(3):485-7.Japanese.PubMedPMID:21403461.

8:ScottLM,ChenL,DanielKG,BrooksWH,GuidaWC,LawrenceHR,SebtiSM,LawrenceNJ,WuJ.Shp2proteintyrosinephosphataseinhibitoractivityofestramustinephosphateanditstriterpenoidanalogs.BioorgMedChemLett.2011Jan15;21(2):730-3.doi:10.1016/j.bmcl.2010.11.117.Epub2010Dec4.PubMedPMID:21193311;PubMedCentralPMCID:PMC3034307.

9:HigashiokaM,YamaguchiE,TakatoriS,TanakaM,KyoiT.[Effectofthe5-HT3receptorantagonistgranisetrononestramustinephosphatesodium(Estracyt)-inducedemesisinferrets].HinyokikaKiyo.2010Jul;56(7):361-5.Japanese.PubMedPMID:20724808.

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