MedKoo Biosciences/Temsirolimus/202870/25mg

Synonym:CCI779;CCI779;CCI779;Temsirolimus;USbrandname:Torisel.

IUPAC/ChemicalName:(1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate.

InChiKey:CBPNZQVSJQDFBE-FUXHJELOSA-N

InChiCode:InChI=1S/C56H87NO16/c1-33-17-13-12-14-18-34(2)45(68-9)29-41-22-20-39(7)56(67,73-41)51(63)52(64)57-24-16-15-19-42(57)53(65)71-46(30-43(60)35(3)26-38(6)49(62)50(70-11)48(61)37(5)25-33)36(4)27-40-21-23-44(47(28-40)69-10)72-54(66)55(8,31-58)32-59/h12-14,17-18,26,33,35-37,39-42,44-47,49-50,58-59,62,67H,15-16,19-25,27-32H2,1-11H3/b14-12+,17-13+,34-18+,38-26+/t33-,35-,36-,37-,39-,40+,41+,42+,44-,45+,46+,47-,49-,50+,56-/m1/s1

SMILESCode:O=C(O[C@H]1[C@H](OC)C[C@H](C[C@H]([C@@H](OC([C@@](CCCC2)([H])N2C(C([C@@]3(O)[C@H](C)CC[C@@](O3)([H])C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@H](OC)[C@H](O)/C(C)=C/[C@H]4C)=O)=O)=O)=O)CC4=O)C)CC1)C(C)(CO)CO

TechnicalData

AdditionalInformation

Temsirolimus(CCI-779)isanintravenousdrugforthetreatmentofrenalcellcarcinoma(RCC),developedbyWyethPharmaceuticalsandapprovedbytheU.S.FoodandDrugAdministration(FDA)inlateMay2007,andwasalsoapprovedbytheEuropeanMedicinesAgency(EMEA)onNovember2007.ItisaderivativeofsirolimusandissoldasTorisel.
 
mTOR(mammaliantargetofrapamycin)isakinaseenzymeinsidethecellthatcollectsandinterpretsthenumerousandvariedgrowthandsurvivalsignalsreceivedbytumorcells.WhenthekinaseactivityofmTORisactivated,itsdownstreameffectors,thesynthesisofcellcycleproteinssuchascyclinDandhypoxia-induciblefactor-1a(HIF-1a)areincreased.HIF-1athenstimulatesVEGF.WhetherornotmTORkinaseisactivated,determineswhetherthetumorcellproduceskeyproteinsneededforproliferation,growth,survival,andangiogenesis.mTORisactivatedintumorcellsbyvariousmechanismsincludinggrowthfactorsurfacereceptortyrosinekinases,oncogenes,andlossoftumorsuppressorgenes.Theseactivatingfactorsareknowntobeimportantformalignanttransformationandprogression.mTORisparticularlyimportantinthebiologyofrenalcancer(RCC)owingtoitsfunctioninregulatingHIF-1alevels.MutationorlossofthevonHippelLindautumor-suppressorgeneiscommoninRCCandismanifestedbyreduceddegradationofHIF-1a.InRCCtumors,activatedmTORfurtherexacerbatesaccumulationofHIF-1abyincreasingsynthesisofthistranscriptionfactoranditsangiogenictargetgeneproducts.TemsirolimusisaspecificinhibitorofmTORandinterfereswiththesynthesisofproteinsthatregulateproliferation,growth,andsurvivaloftumorcells.TreatmentwithtemsirolimusleadstocellcyclearrestintheG1phase,andalsoinhibitstumorangiogenesisbyreducingsynthesisofVEGF. 
 
 

References

 1:Gomez-FernandezC,GardenBC,WuS,FeldmanDR,LacoutureME.Theriskofskinrashandstomatitiswiththemammaliantargetofrapamycininhibitortemsirolimus:asystematicreviewoftheliteratureandmeta-analysis.EurJCancer.2012Feb;48(3):340-6.Epub2011Dec27.Review.PubMedPMID:22206873.

2:DeMassonA,FouchardN,Méry-BossardL,DauendorfferJN.Cutaneousandmucosalaphthosisduringtemsirolimustherapyforadvancedrenalcellcarcinoma:reviewofcutaneousandmucosalsideeffectsofmTORinhibitors.Dermatology.2011;223(1):4-8.Epub2011Aug16.Review.PubMedPMID:21846963.

3:HessG.Temsirolimusforthetreatmentofmantlecelllymphoma.ExpertRevHematol.2009Dec;2(6):631-40.Review.PubMedPMID:21082954.

4:GerullisH,EckeTH,EimerC,HeuckCJ,OttoT.mTOR-inhibitioninmetastaticrenalcellcarcinoma.Focusontemsirolimus:areview.MinervaUrolNefrol.2010Dec;62(4):411-23.Review.PubMedPMID:20944541.

5:HoySM,McKeageK.Temsirolimus:Inrelapsedand/orrefractorymantlecelllymphoma.Drugs.2010Oct1;70(14):1819-29.doi:10.2165/11204940-000000000-00000.Review.PubMedPMID:20836575.

6:NorumJ,NiederC,KondoM.Sunitinib,sorafenib,temsirolimusorbevacizumabinthetreatmentofmetastaticrenalcellcarcinoma:areviewofhealtheconomicevaluations.JChemother.2010Apr;22(2):75-82.Review.PubMedPMID:20435564.

7:RavaudA,BernhardJC,Gross-GoupilM,DigueL,FerriereJM.[mTORinhibitors:temsirolimusandeverolimusinthetreatmentofrenalcellcarcinoma].BullCancer.2010;97:45-51.Review.French.PubMedPMID:20418203.

8:StockC,ZaccagniniM,SchulzeM,TeberD,RassweilerJJ.Temsirolimus.RecentResultsCancerRes.2010;184:189-97.Review.PubMedPMID:20072839.

9:DanceyJE,CurielR,PurvisJ.Evaluatingtemsirolimusactivityinmultipletumors:areviewofclinicaltrials.SeminOncol.2009Dec;36Suppl3:S46-58.Review.PubMedPMID:19963100.

10:HessG,SmithSM,BerkenblitA,CoiffierB.Temsirolimusinmantlecelllymphomaandothernon-Hodgkinlymphomasubtypes.SeminOncol.2009Dec;36Suppl3:S37-45.Review.PubMedPMID:19963099.