Synonym:AG013736;AG013736;AG-013736;Brandname:Inlyta.

IUPAC/ChemicalName:(E)-N-methyl-2-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)benzamide

InChiKey:RITAVMQDGBJQJZ-FMIVXFBMSA-N

InChiCode:InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+

SMILESCode:O=C(NC)C1=CC=CC=C1SC2=CC3=C(C=C2)C(/C=C/C4=NC=CC=C4)=NN3

TechnicalData

AdditionalInformation

Axitinib(alsoknownasAG013736)isasmallmoleculetyrosinekinaseinhibitorunderdevelopmentbyPfizer.Itinhibitsmultipletargets,includingVEGFR-1,VEGFR-2,VEGFR-3,plateletderivedgrowthfactorreceptor(PDGFR),andcKIT(CD117).Ithasbeenshowntosignificantlyinhibitgrowthofbreastcancerinxenograftmodels andhasbeensuccessfulintrialswithrenalcellcarcinoma(RCC) andseveralothertumortypes.
Axitinibisawhitetolight-yellowpowderwithapKaof4.8.ThesolubilityofaxitinibinaqueousmediaovertherangepH1.1topH7.8isinexcessof0.2μg/mL.Thepartitioncoefficient(n-octanol/water)is3.5.
  
APhaseIIclinicaltrialshowedgoodresponseincombinationchemotherapywithGemcitABIneforadvancedpancreaticcancer.However,PfizerreportedonJanuary30,2009thatPhaseIIIclinicaltrialsofthedrugwhenusedincombinationwithGemcitabineshowednoevidenceofimprovedsurvivalratesovertreatmentsusingGemcitabinealoneforadvancedpancreaticcancerandhaltedthetrial. seehttp://en.wikipedia.org/wiki/Axitinib.
 
 

References

1:GunnarssonO,PfanzelterNR,CohenRB,KeefeSM.Evaluatingthesafetyandefficacyofaxitinibinthetreatmentofadvancedrenalcellcarcinoma.CancerManagRes.2015Feb11;7:65-73.doi:10.2147/CMAR.S74202.eCollection2015.Review.PubMedPMID:25709499;PubMedCentralPMCID:PMC4334173.

2:TzoganiK,SkibeliV,WestgaardI,DalhusM,ThoresenH,SlotKB,DamkierP,HoflandK,BorregaardJ,ErsbøllJ,SalmonsonT,PietersR,SylvesterR,MickischG,BerghJ,PignattiF.TheEuropeanMedicinesAgencyApprovalofAxitinib(Inlyta)fortheTreatmentofAdvancedRenalCellCarcinomaAfterFailureofPriorTreatmentWithSunitiniboraCytokine:SummaryoftheScientificAssessmentoftheCommitteeforMedicinalProductsforHumanUse.Oncologist.2015Feb;20(2):196-201.Epub2015Jan23.Review.PubMedPMID:25616431;PubMedCentralPMCID:PMC4319625.

3:BorstDL,ArrudaLS,MacLeanE,PithavalaYK,MorgadoJE.Commonquestionsregardingclinicaluseofaxitinibinadvancedrenalcellcarcinoma.AmJHealthSystPharm.2014Jul1;71(13):1092-6.doi:10.2146/ajhp130581.Review.PubMedPMID:24939498.

4:VerzoniE,GrassiP,TestaI,IacovelliR,BiondaniP,GaranziniE,DeBraudF,ProcopioG.Targetedtreatmentsinadvancedrenalcellcarcinoma:focusonaxitinib.PharmgenomicsPersMed.2014Mar27;7:107-16.doi:10.2147/PGPM.S37098.eCollection2014.Review.PubMedPMID:24715765;PubMedCentralPMCID:PMC3977458.

5:BracardaS,CastellanoD,ProcopioG,SepúlvedaJM,SisaniM,VerzoniE,SchmidingerM.Axitinibsafetyinmetastaticrenalcellcarcinoma:suggestionsfordailyclinicalpracticebasedoncasestudies.ExpertOpinDrugSaf.2014Apr;13(4):497-510.doi:10.1517/14740338.2014.888413.Review.PubMedPMID:24641566.

6:AkazaH,FukuyamaT.Axitinibforthetreatmentofadvancedrenalcellcarcinoma.ExpertOpinPharmacother.2014Feb;15(2):283-97.doi:10.1517/14656566.2014.868436.Epub2013Dec13.Review.PubMedPMID:24328549.

7:Gross-GoupilM,FrançoisL,QuivyA,RavaudA.Axitinib:areviewofitssafetyandefficacyinthetreatmentofadultswithadvancedrenalcellcarcinoma.ClinMedInsightsOncol.2013Oct29;7:269-77.doi:10.4137/CMO.S10594.Review.PubMedPMID:24250243;PubMedCentralPMCID:PMC3825605.

8:ChenY,TortoriciMA,GarrettM,HeeB,KlamerusKJ,PithavalaYK.Clinicalpharmacologyofaxitinib.ClinPharmacokinet.2013Sep;52(9):713-25.doi:10.1007/s40262-013-0068-3.Review.PubMedPMID:23677771.

9:QiWX,HeAN,ShenZ,YaoY.Incidenceandriskofhypertensionwithanovelmulti-targetedkinaseinhibitoraxitinibincancerpatients:asystematicreviewandmeta-analysis.BrJClinPharmacol.2013Sep;76(3):348-57.doi:10.1111/bcp.12149.Review.PubMedPMID:23617405;PubMedCentralPMCID:PMC3769663.

10:KingJW,LeeSM.Axitinibforthetreatmentofadvancednon-small-celllungcancer.ExpertOpinInvestigDrugs.2013Jun;22(6):765-73.doi:10.1517/13543784.2013.775243.Epub2013Mar1.Review.PubMedPMID:23452008.