MedKoo Biosciences/Celecoxib/200700/50mg

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

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
 
 

References

1:DerryS,MooreRA.Singledoseoralcelecoxibforacutepostoperativepaininadults.CochraneDatabaseSystRev.2012Mar14;3:CD004233.Review.PubMedPMID:22419293.

2:WinfieldLL,Payton-StewartF.CelecoxibandBcl-2:emergingpossibilitiesforanticancerdrugdesign.FutureMedChem.2012Mar;4(3):361-83.Review.PubMedPMID:22393942;PubMedCentralPMCID:PMC3398981.

3:McCormackPL.Celecoxib:areviewofitsuseforsymptomaticreliefinthetreatmentofosteoarthritis,rheumatoidarthritisandankylosingspondylitis.Drugs.2011Dec24;71(18):2457-89.doi:10.2165/11208240-000000000-00000.Review.PubMedPMID:22141388.

4:ArakawaY,NakaiN,KatohN.Celecoxib-inducederythemamultiforme-typedrugeruptionwithapositivepatchtest.JDermatol.2011Dec;38(12):1185-8.doi:10.1111/j.1346-8138.2010.01182.x.Epub2011Mar21.Review.PubMedPMID:22103805.

5:MallenSR,EssexMN,ZhangR.GastrointestinaltolerabilityofNSAIDsinelderlypatients:apooledanalysisof21randomizedclinicaltrialswithcelecoxibandnonselectiveNSAIDs.CurrMedResOpin.2011Jul;27(7):1359-66.Epub2011May12.Review.PubMedPMID:21561397.

6:SakamotoC,SoenS.Efficacyandsafetyoftheselectivecyclooxygenase-2inhibitorcelecoxibinthetreatmentofrheumatoidarthritisandosteoarthritisinJapan.Digestion.2011;83(1-2):108-23.Epub2010Nov1.Review.PubMedPMID:21042022.

7:AmriteA,PugazhenthiV,CheruvuN,KompellaU.Deliveryofcelecoxibfortreatingdiseasesoftheeye:influenceofpigmentanddiabetes.ExpertOpinDrugDeliv.2010May;7(5):631-45.Review.PubMedPMID:20205602;PubMedCentralPMCID:PMC2858240.

8:DuboisRN.New,long-terminsightsfromtheAdenomaPreventionwithCelecoxibTrialonapromisingbuttroubledclassofdrugs.CancerPrevRes(Phila).2009Apr;2(4):285-7.Epub2009Mar31.Review.PubMedPMID:19336723.

9:FakihMG,RustumYM.Doescelecoxibhavearoleinthetreatmentofpatientswithcolorectalcancer?ClinColorectalCancer.2009Jan;8(1):11-4.Review.PubMedPMID:19203891.

10:O'ConnorJP,LyszT.Celecoxib,NSAIDsandtheskeleton.DrugsToday(Barc).2008Sep;44(9):693-709.Review.PubMedPMID:19137124.