leucine rich repeat kinase 2 | Leucinerich repeat kinase (LRRK) family | IUPHAR/BPS Guide to PHARMACOLOGY

Park8|Parkinsondisease(autosomaldominant)8|ROCO2|RIPK7|leucine-richrepeatkinase2
Description:StructureoftheROCdomainfromtheParkinson"sdisease-associatedleucine-richrepeatkinase2revealsadimericGTPase
Description:CrystalstructureofMST3withapyrrolopyrimidineinhibitor(PF-06454589).
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
Clinically-RelevantMutationsandPathophysiology
Synonyms:HereditaryParkinsondiseasewithlate-onset[Orphanet:ORPHA411602]
Parkinson"sdisease[DiseaseOntology:DOID:14330]
1.AnastassiADIsT,DeaconSW,DevarajanK,MaH,PetersonJR.(2011)Comprehensiveassayofkinasecatalyticactivityrevealsfeaturesofkinaseinhibitorselectivity.
2.BarkerMD,LiddleJ,AtkinsonFL,WilsonDM,DicksonMC,Ramirez-MolinaC,LewisH,DavisRP,SomersDO,NeuMetal..(2018)DiscoveryofpotentandselectiveSpleenTyrosineKinaseinhibitorsforthetopicaltreatmentofinflammatoryskindisease.
3.BrightbillHD,SutoE,BlaquiereN,RamamoorthiN,Sujatha-BhaskarS,GogolEB,CastanedoGM,JacksonBT,KwonYC,HallerSetal..(2018)NF-κBinducingkinaseisatherapeutictargetforsystemiclupuserythematosus.
4.ChenH,ChanBK,DrummondJ,EstradaAA,Gunzner-TosteJ,LiuX,LiuY,MoffatJ,ShoreD,SweeneyZKetal..(2012)DiscoveryofselectiveLRRK2inhibitorsguidedbycomputationalanalysisandmolecularmodeling.
5.DavisMI,HuntJP,HerrgardS,CiceriP,WodickaLM,PallaresG,HockerM,TreiberDK,ZarrinkarPP.(2011)Comprehensiveanalysisofkinaseinhibitorselectivity.
6.DengJ,LewisPA,GreggioE,SluchE,BeilinaA,CooksonMR.(2008)StructureoftheROCdomainfromtheParkinson"sdisease-associatedleucine-richrepeatkinase2revealsadimericGTPase.
7.DengX,DzamkoN,PrescottA,DaviesP,LiuQ,YangQ,LeeJD,PatricelliMP,NomanbhoyTK,AlessiDRetal..(2011)CharacterizationofaselectiveinhibitoroftheParkinson"sdiseasekinaseLRRK2.
8.EstradaAA,ChanBK,Baker-GlennC,BeresfordA,BurdickDJ,ChambersM,ChenH,DominguezSL,DotsonJ,DrummondJetal..(2014)Discoveryofhighlypotent,selective,andbrain-penetrantaminopyrazoleleucine-richrepeatkinase2(LRRK2)smallmoleculeinhibitors.
9.GoodfellowVS,LowethCJ,RavulaSB,WiemannT,NguyenT,XuY,ToddDE,SheppardD,PollackS,PolesskayaOetal..(2013)Discovery,synthesis,andcharacterizationofanorallybioavailable,brainpenetrantinhibitorofmixedlineagekinase3.
10.HendersonJL,KormosBL,HaywardMM,CoffmanKJ,JastiJ,KurumbailRG,WagerTT,VerhoestPR,NoellGS,ChenYetal..(2015)DiscoveryandPreclinicalProfilingof3-[4-(Morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile(PF-06447475),aHighlyPotent,Selective,BrainPenetrant,andinVivoActiveLRRK2KinaseInhibitor.
11.KavanaghME,DoddareddyMR,KassiouM.(2013)ThedevelopmentofCNS-activeLRRK2inhibitorsusingproperty-directedoptimisation.
12.RiggsJR,ElsnerJ,CashionD,RobinsonD,TehraniL,NagyM,FultzKE,KrishnaNarlaR,PengX,TranTetal..(2019)DesignandOptimizationLeadingtoanOrallyActiveTTKProteinKinaseInhibitorwithRobustSingleAgentEfficacy.
13.WodickaLM,CiceriP,DavisMI,HuntJP,FloydM,SalernoS,HuaXH,FordJM,ArmstrongRC,ZarrinkarPPetal..(2010)Activationstate-dependentbindingofsmallmoleculekinaseinhibitors:structuralinsightsfrombiochemistry.
Leucine-richrepeatkinase(LRRK)family:leucinerichrepeatkinase2.Lastmodifiedon10/06/2019.Accessedon18/05/2020.IUPHAR/BPSGuidetoPHARMACOLOGY,http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2059.