Synonym:ZD1839;ZD1839;ZD-1839;Gefitinib;USbrandname:Iressa.

IUPAC/ChemicalName:N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine

InChiKey:XGALLCVXEZPNRQ-UHFFFAOYSA-N

InChiCode:InChI=1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h4-4,11-14H,2,5-10H2,1H3,(H,25,26,27)

SMILESCode:COC1=CC2=NC=NC(NC3=CC=C(F)C(Cl)=C3)=C2C=C1OCCCN4CCOCC4

TechnicalData

AdditionalInformation

 
Accordingtohttp://en.wikipedia.org/wiki/Gefitinib,Gefitinibisthefirstselectiveinhibitorofepidermalgrowthfactorreceptor's(EGFR)tyrosinekinasedomain.ThusgefitinibisanEGFRinhibitor.Thetargetprotein(EGFR)isalsosometimesreferredtoasHer1orErbB-1dependingontheliteraturesource.EGFRisoverexpressedinthecellsofcertaintypesofhumancarcinomas-forexampleinlungandbreastcancers.Thisleadstoinappropriateactivationoftheanti-apoptoticRassignallingcascade,eventuallyleADIngtouncontrolledcellproliferation.Researchongefitinib-sensitivenon-smallcelllungcancershasshownthatamutationintheEGFRtyrosinekinasedomainisresponsIBLeforactivatinganti-apoptoticpathways. Thesemutationstendtoconferincreasedsensitivitytotyrosinekinaseinhibitorssuchasgefitinibanderlotinib.Ofthetypesofnon-smallcelllungcancerhistologies,adenocarcinomaisthetypethatmostoftenharborsthesemutations.ThesemutationsaremorecommonlyseeninAsians,women,andnon-smokers(whoalsotendtomoreoftenhaveadenocarcinoma).GefitinibinhibitsEGFRtyrosinekinasebybindingtotheadenosinetriphosphate(ATP)-bindingsiteoftheenzyme.ThusthefunctionoftheEGFRtyrosinekinaseinactivatingtheRassignaltransductioncascadeisinhibited,andmalignantcellsareinhibited.
 
 
Gefitinibiscurrentlyonlyindicatedforthetreatmentoflocallyadvancedormetastaticnon-smallcelllungcancer(NSCLC)inpatientswhohavepreviouslyreceivedchemotherapy.Whilegefitinibhasyettobeproventobeeffectiveinothercancers,thereispotentialforitsuseinthetreatmentofothercancerswhereEGFRoverexpressionisinvolved. In2004,AstraZenecainformedtheUnitedStatesFoodandDrugAdmiNISTration(FDA)thatalargerandomizedstudyfailedtodemonstrateasurvivaladvantageforgefitinibinthetreatmentofnon-smallcelllungcancer(NSCLC).Whetherprogression-freesurvivalisprolongedisnotclearfromthisstatement.AstraZenecaalsowithdrewtheirapplicationtomarketgefitinibinEuropeshortlyafterthisannouncement.ErlotinibisanotherEGFRtyrosinekinaseinhibitorthatworksinthesamewayasgefitinib.Giventhelackofsurvivaladvantageforgefitinibandthepositiveresultsforerlotinib,erlotinibhasreplacedgefitinibintheUnitedStates(exceptinpatientswheregefitinibhashadaprovenresponse).
Gefitinibiscurrentlyonlyindicatedforthetreatmentoflocallyadvancedormetastaticnon-smallcelllungcancer(NSCLC)inpatientswhohavepreviouslyreceivedchemotherapy.Whilegefitinibhasyettobeproventobeeffectiveinothercancers,thereispotentialforitsuseinthetreatmentofothercancerswhereEGFRoverexpressionisinvolved. In2004,AstraZenecainformedtheUnitedStatesFoodandDrugAdministration(FDA)thatalargerandomizedstudyfailedtodemonstrateasurvivaladvantageforgefitinibinthetreatmentofnon-smallcelllungcancer(NSCLC).Whetherprogression-freesurvivalisprolongedisnotclearfromthisstatement.AstraZenecaalsowithdrewtheirapplicationtomarketgefitinibinEuropeshortlyafterthisannouncement.ErlotinibisanotherEGFRtyrosinekinaseinhibitorthatworksinthesamewayasgefitinib.Giventhelackofsurvivaladvantageforgefitinibandthepositiveresultsforerlotinib,erlotinibhasreplacedgefitinibintheUnitedStates(exceptinpatientswheregefitinibhashadaprovenresponse).

References

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