2022
Defining the structure-activity relationship for a novel class of allosteric MKP5 inhibitors
Gannam Z, Jamali H, Kweon OS, Herrington J, Shillingford SR, Papini C, Gentzel E, Lolis E, Bennett AM, Ellman JA, Anderson KS. Defining the structure-activity relationship for a novel class of allosteric MKP5 inhibitors. European Journal Of Medicinal Chemistry 2022, 243: 114712. PMID: 36116232, PMCID: PMC9830533, DOI: 10.1016/j.ejmech.2022.114712.Peer-Reviewed Original ResearchMeSH KeywordsStructure-Activity RelationshipConceptsStress-responsive MAPKsEnzyme-inhibitor complexDystrophic muscle diseasePhosphatase 5Muscle diseaseAllosteric inhibitorsNumber of diseasesNovel classProtein kinase phosphatase 5Structure-activity relationshipsPotential therapeutic targetMKP5X-ray crystal structureTherapeutic targetPotential therapeuticsInhibitorsLead compoundsInhibitionProper positioningMAPKCrystal structureMitogenTyr435Derivative compoundsInteraction
2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2013
Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5
Shi H, Verma M, Zhang L, Dong C, Flavell RA, Bennett AM. Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5. Journal Of Clinical Investigation 2013, 123: 2064-2077. PMID: 23543058, PMCID: PMC3635719, DOI: 10.1172/jci64375.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCrosses, GeneticDual-Specificity PhosphatasesDystrophinFemaleMaleMAP Kinase Kinase 4MAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMuscle, SkeletalMusclesMuscular Dystrophy, DuchenneMutationP38 Mitogen-Activated Protein KinasesRegenerationStem CellsConceptsMuscle stem cell functionMitogen-activated protein kinaseStem cell functionMKP-5MAPK phosphataseSkeletal muscle diseasesRegenerative myogenesisCell functionMuscle stem cell proliferationP38 mitogen-activated protein kinaseMuscle stem cellsDegenerative skeletal muscle diseaseStem cell proliferationEssential negative regulatorProtein kinaseMuscle diseaseNegative regulatorMAPK activityGenetic lossMKP5Muscle phenotypeDystrophic muscle phenotypeStem cellsMuscular dystrophyCell proliferation