Invitro | Y16bindstothejunctionsiteoftheDH-PHdomainsofLARGwitha∼80nMKdandsuppressesLARGcatalyzedRhoAactivationdosedependently.ItisactiveinblockingtheinteractionofLARGandrelatedG-protein–coupledRhoGEFswithRhoAwithoutadetectableeffectonotherDBLfamilyRhoGEFs,Rhoeffectors,oraRhoGAP.Incells,Y16selectivelyinhibitsserum-inducedRhoAactivityandRhoA-mediatedsignaling,effectsthatcanberescuedbyaconstitutivelyactiveRhoAorROCKmutant.BysuppressingRhoAactivity,Y16inhibitsmammarysphereformationofMCF7breastcancercellsbutdoesnotaffectthenontransformingMCF10Acells.Y16workssynergisticallywithRhosin/G04,aRhoGTPaseactivationsiteinhibitor,ininhibitingLARG–RhoAinteraction,RhoAactivation,andRhoA-mediatedsignalingfunctions.Y16effectivelyinhibitsthegrowth,migration,andinvasionactivitiesofbreastcancercells[1]. |
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