aurora kinase A | Aurora kinase (Aur) family | IUPHAR/BPS Guide to PHARMACOLOGY

ARK1|AurA|Aurora2|Aurorafamilykinase1|ratAurA|serine/threoninekinase15|serine/threoninekinase6|STK15|STK6
Downloadallstructure-activitydataforthistargetasaCSVfile
EMDMilliporeKinaseProfilerTMscreen/ReactionBIOLOGyKinaseHotspotSMscreen
Ascreenprofiling158kinaseinhibitors(CalbiochemProteinKinaseInhibitorLibraryIandII,cataloguenumbers539744and539745)fortheirinhibitoryactivityat1Mand10Magainst234humanrecombinantkinasesusingtheEMDMilliporeKinaseProfilerTMservice.

Ascreenprofilingtheinhibitoryactivityof178commerciallyavailablekinaseinhibitorsat0.5Magainstapanelof300recombinantproteinkinasesusingtheReactionBiologyCorporationKinaseHotspotSMplatform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx
AurorakinaseAlocalisestothecentrosomesduringDNAduplicationintheSphaseandmigratestospindlepolesduringmitosis.
AurorakinaseAplaysacentralroleincentrosomeregulationandmitoticspindleformation.
PhysiologicalConsequencesofAlteringGeneExpression
AurorakinaseAknock-outmicearenotviable.Aurka−/−embryosdiebeforethe16-cellstage.
Clinically-RelevantMutationsandPathophysiology
1.AdamsND,AdamsJL,BurgessJL,ChaudhariAM,CopelandRA,DonatelliCA,DrewryDH,FisherKE,HamajimaT,HardwickeMAetal..(2010)DiscoveryofGSK1070916,apotentandselectiveinhibitorofAuroraB/Ckinase.
2.Aliagas-MartinI,BurdickD,CorsonL,DotsonJ,DrummondJ,FieldsC,HuangOW,HunsakerT,KleinheinzT,KruegerEetal..(2009)Aclassof2,4-bisanilinopyrimidineAuroraAinhibitorswithunusuallyhighselectivityagainstAuroraB.
3.AnastassiADIsT,DeaconSW,DevarajanK,MaH,PetersonJR.(2011)Comprehensiveassayofkinasecatalyticactivityrevealsfeaturesofkinaseinhibitorselectivity.
4.AronovAM,TangQ,Martinez-BotellaG,BemisGW,CaoJ,ChenG,EwingNP,FordPJ,GermannUA,GreenJetal..(2009)Structure-guideddesignofpotentandselectivepyrimidylpyrroleinhibitorsofextracellularsignal-regulatedkinase(ERK)usingconformationalcontrol.
5.BarkerMD,LiddleJ,AtkinsonFL,WilsonDM,DicksonMC,Ramirez-MolinaC,LewisH,DavisRP,SomersDO,NeuMetal..(2018)DiscoveryofpotentandselectiveSpleenTyrosineKinaseinhibitorsforthetopicaltreatmentofinflammatoryskindisease.
6.BebbingtonD,BinchH,CharrierJD,EverittS,FraysseD,GolecJ,KayD,KnegtelR,MakC,MazzeiFetal..(2009)ThediscoveryofthepotentaurorainhibitorMK-0457(VX-680).
7.BelangerDB,WilliamsMJ,CurranPJ,MandalAK,MengZ,RainkaMP,YuT,ShihNY,SiddiquiMA,LiuMetal..(2010)Discoveryoforallybioavailableimidazo[1,2-a]pyrazine-basedAurorakinaseinhibitors.
8.BindiS,FancelliD,AlliC,BertaD,BertrandJA,CameronAD,CappellaP,CarpinelliP,CerviG,CrociVetal..(2010)Thieno[3,2-c]pyrazoles:anovelclassofAurorainhibitorswithfavorableantitumoractivity.
9.CeeVJ,ChengAC,RomeroK,BellonS,MohrC,WhittingtonDA,BakA,BreadyJ,CaenepeelS,CoxonAetal..(2009)Pyridyl-pyrimidinebenzimidazolederivativesaspotent,selective,andorallybioavailableinhibitorsofTie-2kinase.
10.DavisMI,HuntJP,HerrgardS,CiceriP,WodickaLM,PallaresG,HockerM,TreiberDK,ZarrinkarPP.(2011)Comprehensiveanalysisofkinaseinhibitorselectivity.
11.DitchfieldC,JohnsonVL,TigheA,EllstonR,HaworthC,JohnsonT,MortlockA,KeenN,TaylorSS.(2003)AuroraBcoupleschromosomealignmentwithanaphasebytargetingBubR1,Mad2,andCenp-Etokinetochores.
12.FancelliD,MollJ,VarasiM,BravoR,ArticoR,BertaD,BindiS,CameronA,CandianiI,CappellaPetal..(2006)1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles:identificationofapotentAurorakinaseinhibitorwithafavorableantitumorkinaseinhibitionprofile.
13.FedorovO,MarsdenB,PogacicV,RellosP,MüllerS,BullockAN,SchwallerJ,SundströmM,KnappS.(2007)AsystematicinteractionmapofvalidatedkinaseinhibitorswithSer/Thrkinases.
14.FuJ,BianM,JiangQ,ZhangC.(2007)RolesofAurorakinasesinmitosisandtumOrigenesis.
15.GaoY,DaviesSP,AugustinM,WoodwardA,PatelUA,KovelmanR,HarveyKJ.(2013)Abroadactivityscreeninsupportofachemogenomicmapforkinasesignallingresearchanddrugdiscovery.
16.GlaserKB,LiJ,MarcottePA,MagocTJ,GuoJ,ReuterDR,TapangP,WeiRQ,PeaseLJ,BuiMHetal..(2012)PreclinicalcharacterizationofABT-348,akinaseinhibitortargetingtheaurora,vascularendothelialgrowthfactorreceptor/platelet-derivedgrowthfactorreceptor,andSrckinasefamilies.
17.HarringtonEA,BebbingtonD,MooreJ,RasmussenRK,Ajose-AdeogunAO,NakayamaT,GrahamJA,DemurC,HercendT,Diu-HercendAetal..(2004)VX-680,apotentandselectivesmall-moleculeinhibitoroftheAurorakinases,suppressestumorgrowthinvivo.
18.HowardS,BerdiniV,BoulstridgeJA,CarrMG,CrossDM,CurryJ,DevineLA,EarlyTR,FazalL,GillALetal..(2009)Fragment-baseddiscoveryofthepyrazol-4-ylurea(AT9283),amultitargetedkinaseinhibitorwithpotentaurorakinaseactivity.
19.JordaR,HendrychováD,VollerJ,ŘezníčkováE,GuckýT,KryštofV.(2018)HowSelectiveArePharmacologicalInhibitorsofCell-Cycle-RegulatingCyclin-DependentKinases?.
20.JungFH,PasquetG,Lambert-vanderBremptC,LohmannJJ,WarinN,RenaudF,GermainH,DeSaviC,RobertsN,JohnsonTetal..(2006)DiscoveryofnovelandpotentthiazoloquinazolinesasselectiveAuroraAandBkinaseinhibitors.
21.LiddleJ,AtkinsonFL,BarkerMD,CarterPS,CurtisNR,DavisRP,DouaultC,DicksonMC,ElwesD,GartonNSetal..(2011)DiscoveryofGSK143,ahighlypotent,selectiveandorallyefficaciousspleentyrosinekinaseinhibitor.
22.LuLY,WoodJL,YeL,Minter-DykhouseK,SaundersTL,YuX,ChenJ.(2008)AuroraAisessentialforearlyembryonicdevelopmentandtumorsuppression.
23.ManfrediMG,EcsedyJA,MeetzeKA,BalaniSK,BurenkovaO,ChenW,GalvinKM,HoarKM,HuckJJ,LeRoyPJetal..(2007)AntitumoractivityofMLN8054,anorallyactivesmall-moleculeinhibitorofAuroraAkinase.
24.MedinaJR,BeckerCJ,BlackledgeCW,DuquenneC,FengY,GrantSW,HeerdingD,LiWH,MillerWH,RomerilSPetal..(2011)Structure-baseddesignofpotentandselective3-phosphoinositide-dependentkinase-1(PDK1)inhibitors.
25.MollardA,WarnerSL,CallLT,WadeML,BearssJJ,VermaA,SharmaS,VankayalapatiH,BearssDJ.(2011)Design,SynthesisandBiologicalEvaluationofaSeriesofNovelAxlKinaseInhibitors.
26.NowakowskiJ,CroninCN,McReeDE,KnuthMW,NelsonCG,PavletichNP,RogersJ,SangBC,ScheibeDN,SwansonRVetal..(2002)Structuresofthecancer-relatedAurora-A,FAK,andEphA2proteinkinasesfromnanovolumecrystallography.
27.OslobJD,RomanowskiMJ,AllenDA,BaskaranS,BuiM,EllingRA,FlanaganWM,FungAD,HananEJ,HarrisSetal..(2008)Discoveryofapotentandselectiveaurorakinaseinhibitor.
28.PaytonM,BushTL,ChungG,ZieglerB,EdenP,McElroyP,RossS,CeeVJ,DeakHL,HodousBLetal..(2010)PreclinicalevaluationofAMG900,anovelpotentandhighlyselectivepan-aurorakinaseinhibitorwithactivityintaxane-resistanttumorcelllines.
29.PollardJR,MortimoreM.(2009)Discoveryanddevelopmentofaurorakinaseinhibitorsasanticanceragents.
30.RobertsWG,UngE,WhalenP,CooperB,HulfordC,AutryC,RichterD,EmersonE,LinJ,KathJetal..(2008)Antitumoractivityandpharmacologyofaselectivefocaladhesionkinaseinhibitor,PF-562,271.
31.SchlapbachA,FeifelR,HawtinS,HengR,KochG,MoebitzH,ReveszL,ScheuflerC,VelcickyJ,WaelchliRetal..(2008)Pyrrolo-pyrimidones:anovelclassofMK2inhibitorswithpotentcellularactivity.
32.ShimomuraT,HasakoS,NakatsuruY,MitaT,IchikawaK,KoderaT,SakaiT,NambuT,MiyamotoM,TakahashiIetal..(2010)MK-5108,ahighlyselectiveAurora-Akinaseinhibitor,showsantitumoractivityaloneandincombinationwithdocetaxel.
33.ShiotsuY,KiyoiH,IshikawaY,TanizakiR,ShimizuM,UmeharaH,IshiiK,MoriY,OzekiK,MinamiYetal..(2009)KW-2449,anovelmultikinaseinhibitor,suppressesthegrowthofleukemiacellswithFLT3mutationsorT315I-mutatedBCR/ABLtranslocation.
34.TamuraM,NakaoH,YoshizakiH,ShiratsuchiM,ShigyoH,YamadaH,OzawaT,TotsukaJ,HidakaH.(2005)DevelopmentofspecificRho-kinaseinhibitorsandtheirclinicalapplication.
35.TariLW,HoffmanID,BensenDC,HunterMJ,NixJ,NelsonKJ,McReeDE,SwansonRV.(2007)StructuralbasisfortheinhibitionofAuroraAkinasebyanovelclassofhighaffinitydisubstitutedpyrimidineinhibitors.
36.TovarC,HigginsB,DeoD,KolinskyK,LiuJJ,HeimbrookDC,VassilevLT.(2010)Small-moleculeinducerofcancercellpolyploidypromotesapoptosisorsenescence:Implicationsfortherapy.
37.WodickaLM,CiceriP,DavisMI,HuntJP,FloydM,SalernoS,HuaXH,FordJM,ArmstrongRC,ZarrinkarPPetal..(2010)Activationstate-dependentbindingofsmallmoleculekinaseinhibitors:structuralinsightsfrombiochemistry.
38.YangJ,IkezoeT,NishiokaC,TasakaT,TaniguchiA,KuwayamaY,KomatsuN,BandobashiK,TogitaniK,KoefflerHPetal..(2007)AZD1152,anovelandselectiveauroraBkinaseinhibitor,inducesgrowtharrest,apoptosis,andsensitizationfortubulindepolymerizingagentortopoisomeraseIIinhibitorinhumanacuteleukemiacellsinvitroandinvivo.
Aurorakinase(Aur)family:aurorakinaseA.Lastmodifiedon12/04/2019.Accessedon18/05/2020.IUPHAR/BPSGuidetoPHARMACOLOGY,http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1936.