CelecoxibwasdevelopedbyG.D.Searle&Companyandco-promotedbyMonsantoCompany(parentcompanyofSearle)andPfizerunderthebrandnameCelebrex.MonsantomergedwithPharmacia,fromwhichtheMedicalResearchDivisionwasacquiredbyPfizer,givingPfizerownershipofCelebrex.ThedrugwasatthecoreofamajorpatentdisputethatwasresolvedinSearlesfavor(laterPfizer)in2004.InUniversityofRochesterv.G.D.Searle&Co.,358F.3d916(Fed.Cir.2004),theUniversityofRochesterclaimedthatUnitedStatesPat.No.6,048,850(whichclaimedamethodofinhibitingCOX-2inhumansusingacompound,withoutactuallydisclosingwhatthatcompoundmightbe)covereddrugssuchascelecoxib.ThecourtruledinfavorofSearle,holdinginessencethattheUniversityhadclaimedamethodrequiring,yetprovidednowrittendescriptionof,acompoundthatcouldinhibitCOX-2andthereforethepatentwasinvalid.

MedKooCat#:200700
Name:Celecoxib
CAS#:169590-42-5
ChemicalFormula:C17H14F3N3O2S
ExactMass:381.07588
MolecularWeight:381.37
ElementalAnalysis:C,53.54;H,3.70;F,14.94;N,11.02;O,8.39;S,8.41


Synonym:

IUPAC/ChemicalName:4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide

InChiKey:RZEKVGVHFLEQIL-UHFFFAOYSA-N

InChiCode:InChI=1S/C17H14F3N3O2S/c1-11-2-4-12(5-3-11)15-10-16(17(18,19)20)22-23(15)13-6-8-14(9-7-13)26(21,24)25/h2-10H,1H3,(H2,21,24,25)

SMILESCode:O=S(C1=CC=C(N2N=C(C(F)(F)F)C=C2C3=CC=C(C)C=C3)C=C1)(N)=O


TechnicalData

Appearance:
Solidpowder

Purity:
>98%(orrefertotheCertificateofAnalysis)

ShippingCondition:
Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.

StorageCondition:
Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).

Solubility:
SolubleinDMSO,notinwater

ShelfLife:
>5yearsifstoredproperly

DrugFormulation:
ThisdrugmaybeformulatedinDMSO

StockSolutionStorage:
0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).

HarmonizedSystemCode:
293490


AdditionalInformation

Celecoxibisasulfanon-steroidalanti-inflammatorydrug(NSAID)usedinthetreatmentofosteoarthritis,rheumatoidarthritis,acutepain,painfulmenstruationandmenstrualsymptoms,andtoreducenumbersofcolonandrectumpolypsinpatientswithfamilialadenomatouspolyposis.ItismarketedbyPfizer.ItisknownunderthebrandnameCelebrexorCelebraforarthritisandOnsenalforpolyps.Celecoxibisavailablebyprescriptionincapsuleform.
 
PfizersellscelecoxibunderthebrandnameCelebrex.CelecoxibisnotcurrentlyavailableasagenericintheUnitedStates,becausetheintellectualpropertyisstillcontrolledbyPfizer.However,inothercountries,includingIndiaandthePhilippines,itislegallyavailableasagenericunderthebrandnamesCobixandCelcoxx.XLLaboratoriessellscelecoxibunderthebrandnameSelecapinVietnamandthePhilippines.Seehttp://en.wikipedia.org/wiki/Celecoxib.
 
History
Afterthewithdrawalofrofecoxib(Vioxx)fromthemarketinSeptember2004,Celebrexenjoyedarobustincreaseinsales.However,theresultsoftheAPCtrialinDecemberofthatyearraisedconcernsthatCelebrexmightcarryriskssimilartothoseofVioxx,andPfizerannouncedamoratoriumondirect-to-consumeradvertisingofCelebrexsoonafterwards.Afterasignificantdrop,salesofCelebrexhaverecovered,andreached$2billionin2006. PfizerresumedadvertisingCelebrexinmagazinesin2006, andresumedtelevisionadvertisinginApril2007withanunorthodox,2Å“minuteadvertisementwhichextensivelydiscussedtheadverseeffectsofCelebrexincomparisonwithotheranti-inflammatorydrugs.TheaddrewcriticismfromtheconsumeradvocacygroupPublicCitizen,whichcalledthead'scomparisonsmisleading.PfizerhasrespondedtoPublicCitizen'sconcernswithassurancesthattheyaretruthfullyadvertisingtheriskandbenefitsofCelebrexassetforthbytheFDA.Inlate2007,PfizerreleasedanotherU.S.televisionadforCelebrex,whichalsodiscussedcelecoxib'sadverseeffectsincomparisonwiththoseofotheranti-inflammatorydrugs.Dr.SimmonsofBrighamYoungUniversity,whodiscoveredtheCOX-2enzyme,issuingPfizertobecreditedwithdiscoveryofthetechniquein1989thateventuallyledtothedrug,andfor$1billionUSD,(Thecompanyhasmadeabout$30billionfromthedrugasof2006).
Researchintocancerprevention
Therolethatcelecoxibmighthaveinreducingtheratesofcertaincancershasbeenthesubjectofmanystudies.However,giventhesideeffectsofanti-COX-2onratesofheartdisease,thereisnocurrentmedicalrecommendationtousethisdrugforcancerreduction.ColorectalcancerriskisclearlyreducedinpeopleregularlytakingaNSAIDlikeaspirinorcelecoxib.Inaddition,someepidemiologicalstudies,andmostpreclinicalstudiespointedoutthatspecificCOX-2inhibitorslikecelecoxibaremorepotentandlesstoxicthan"older"NSAIDs.Twelvecarcinogenesisstudiessupportthatcelecoxibisstrikinglypotenttopreventintestinalcancerinratsormice(dataavailableontheChemopreventionDatabase).Small-scaleclinicaltrialsinveryhighriskpeople(belongingtoFAPfamilies)alsoindicatethatcelecoxibcanpreventpolypgrowth.Hencelarge-scalerandomizedclinicaltrialswereundertakenandresultspublishedbyN.ArberandM.BertagnolliintheNewEnglandJournalofMedicine,August2006.Resultsshowa33to45%polyprecurrencereductioninpeopletaking400–800mgcelecoxibeachday.However,seriouscardiovasculareventsweresignificantlymorefrequentinthecelecoxib-treatedgroups(seeabove,cardiovasculartoxicity).Aspirinshowsasimilar(andpossiblylarger)protectiveeffect,hasdemonstratedcardioprotectiveeffectsandissignificantlycheaper,buttherehavebeennohead-to-headclinicaltrialscomparingthetwodrugs.
 
Researchintocancertreatment
Differentfromcancerprevention,cancertreatmentisfocusedonthetherapyoftumorsthathavealreadyformedandhaveestablishedthemselvesinsidethepatient.Manystudiesareongoingtodeterminewhethercelecoxibmightbeusefulforthislattercondition.However,duringmolecularstudiesinthelaboratory,itbecameapparentthatcelecoxibcouldinteractwithotherintracellularcomponentsbesidesitsmostfamoustarget,cyclooxygenase2(COX-2).Thediscoveryoftheseadditionaltargetshasgeneratedmuchcontroversy,andtheinitialassumptionthatcelecoxibreducestumorgrowthprimarilyviatheinhibitionofCOX-2becamecontentious.Certainly,theinhibitionofCOX-2isparamountfortheanti-inflammatoryandanalgesicfunctionofcelecoxib.However,whetherinhibitionofCOX-2alsoplaysadominantroleinthisdrugÂ’santicancereffectsisunclear.Forexample,arecentstudywithmalignanttumorcellsshowedthatcelecoxibcouldinhibitthegrowthofthesecellsinvitro,butCOX-2playednoroleinthisoutcome;evenmorestrikingly,theanticancereffectsofcelecoxibwerealsoobtainedwiththeuseofcancercelltypesthatdonÂ’tevencontainCOX-2.AdditionalsupportfortheideathatothertargetsbesidesCOX-2areimportantforcelecoxib'santicancereffectshascomefromstudieswithchemicallymodifiedversionsofcelecoxib.Severaldozenanalogsofcelecoxibweregeneratedwithsmallalterationsintheirchemicalstructures.SomeoftheseanalogsretainedCOX-2inhibitoryactivity,whereasmanyothersdidn't.However,whentheabilityofallthesecompoundstokilltumorcellsincellculturewasinvestigated,itturnedoutthattheantitumorpotencydidnotatalldependonwhetherornottherespectivecompoundcouldinhibitCOX-2,showingthatinhibitionofCOX-2wasnotrequiredfortheanticancereffects. Oneofthesecompounds,2,5-dimethyl-celecoxib,whichentirelylackstheabilitytoinhibitCOX-2,actuallyturnedouttodisplaystrongeranticanceractivitythancelecoxibitself.
 
Currentdeveloper:  Pfizer
 
 


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