spleen associated tyrosine kinase | Syk family | IUPHAR/BPS Guide to PHARMACOLOGY

Description:StructuralandbiophysicalcharacterizationoftheSykactivationswitch.
Description:CRYSTALSTRUCTUREOFSPLEENTYROSINEKINASE(SYK)INCOMPLEXWITHA2-(PHENOXYMETHYL)PYRIDINEINHIBITOR(GSK26462640.
Downloadallstructure-activitydataforthistargetasaCSVfile

Description:AssayedusingN-FlagtaggedcatalyticdomainofhumanSYK(Ala340-Asn635)

Description:MeasuringinhibitionofthecapacityofatruncatedconstructofSyk(aa360-635)tophosphorylateabiotinylatedpeptidesubstrate.
EMDMilliporeKinaseProfilerTMscreen/ReactionBIOLOGyKinaseHotspotSMscreen
Ascreenprofiling158kinaseinhibitors(CalbiochemProteinKinaseInhibitorLibraryIandII,cataloguenumbers539744and539745)fortheirinhibitoryactivityat1Mand10Magainst234humanrecombinantkinasesusingtheEMDMilliporeKinaseProfilerTMservice.

Ascreenprofilingtheinhibitoryactivityof178commerciallyavailablekinaseinhibitorsat0.5Magainstapanelof300recombinantproteinkinasesusingtheReactionBiologyCorporationKinaseHotspotSMplatform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx
SYKplaysakeyroleincouplingactivatedimmunoreceptorstodownstreamcellularresponsessuchasproliferation,differentiation,andphagocytosis.Mastcell,macrophageandB-cellactivation(andreleaseofinflammatorymodulators)isdisruptedbyinhibitionofSYK-mediatedimmunoreceptorsignalling.SelectiveSYKinhibitorsarebeingsoughtforanumberofinflammatoryconditionsincludingrheumatoidarthritis,B-celllymphomaandasthma/rhinitis[11,22].

ThefirstSYKinhibitortoreceiveFDAapprovalwasfostamatinib(April2018),whichwasauthorisedforthetreatmentofpersistent/chronicadultimmunethrombocytopenia(ITP)[21].InITP,SYK-mediatedsignaltransductioninmacrophagesdrivesthephagocytosisanddestructionofautoantibody-coatedplatelets.
GO:0045425positiveregulationofgranulocytemacrophagecolony-stimulatingfactorbiosyntheticprocess
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Sykfamily:spleenassociatedtyrosinekinase.Lastmodifiedon12/03/2019.Accessedon18/05/2020.IUPHAR/BPSGuidetoPHARMACOLOGY,http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2230.