FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2136060128> ?p ?o ?g. }

• W2136060128 endingPage "359" @default.
• W2136060128 startingPage "350" @default.
• W2136060128 abstract "Based on genetic studies that establish the role of spleen tyrosine kinase (Syk) in immune function, inhibitors of this kinase are being investigated as therapeutic agents for inflammatory diseases. Because genetic studies eliminate both adapter functions and kinase activity of Syk, it is difficult to delineate the effect of kinase inhibition alone as would be the goal with small-molecule kinase inhibitors. We tested the hypothesis that specific pharmacological inhibition of Syk activity retains the immunomodulatory potential of Syk genetic deficiency. We report here on the discovery of (4-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-2-((1R,2S)-2-aminocyclohexylamino) pyrimidine-5-carboxamide acetate (P505-15), a highly specific and potent inhibitor of purified Syk (IC50 1-2 nM). In human whole blood, P505-15 potently inhibited B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM). Similar levels of ex vivo inhibition were measured after dosing in mice (Syk signaling IC50 0.32 μM). Syk-independent signaling and activation were unaffected at much higher concentrations, demonstrating the specificity of kinase inhibition in cellular systems. Oral administration of P505-15 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. Statistically significant efficacy was observed at concentrations that specifically suppressed Syk activity by ∼67%. Thus specific Syk inhibition can mimic Syk genetic deficiency to modulate immune function, providing a therapeutic strategy in P505-15 for the treatment of human diseases." @default.
• W2136060128 created "2016-06-24" @default.
• W2136060128 creator A5000641347 @default.
• W2136060128 creator A5013834732 @default.
• W2136060128 creator A5014527416 @default.
• W2136060128 creator A5017059863 @default.
• W2136060128 creator A5020422833 @default.
• W2136060128 creator A5020860588 @default.
• W2136060128 creator A5026142305 @default.
• W2136060128 creator A5028670333 @default.
• W2136060128 creator A5053159281 @default.
• W2136060128 creator A5063895679 @default.
• W2136060128 creator A5068917225 @default.
• W2136060128 creator A5080730505 @default.
• W2136060128 creator A5084300737 @default.
• W2136060128 date "2011-10-31" @default.
• W2136060128 modified "2023-10-06" @default.
• W2136060128 title "Specific Inhibition of Spleen Tyrosine Kinase Suppresses Leukocyte Immune Function and Inflammation in Animal Models of Rheumatoid Arthritis" @default.
• W2136060128 cites W104872243 @default.
• W2136060128 cites W1964842624 @default.
• W2136060128 cites W1965319674 @default.
• W2136060128 cites W1970663543 @default.
• W2136060128 cites W1972593274 @default.
• W2136060128 cites W1976058906 @default.
• W2136060128 cites W1976912963 @default.
• W2136060128 cites W1979816280 @default.
• W2136060128 cites W1983513155 @default.
• W2136060128 cites W1986029666 @default.
• W2136060128 cites W1995629350 @default.
• W2136060128 cites W2001263473 @default.
• W2136060128 cites W2015791855 @default.
• W2136060128 cites W2017341404 @default.
• W2136060128 cites W2036782719 @default.
• W2136060128 cites W2043823402 @default.
• W2136060128 cites W2050069950 @default.
• W2136060128 cites W2087947799 @default.
• W2136060128 cites W2088757697 @default.
• W2136060128 cites W2089783130 @default.
• W2136060128 cites W2095726706 @default.
• W2136060128 cites W2101217991 @default.
• W2136060128 cites W2107821023 @default.
• W2136060128 cites W2116382435 @default.
• W2136060128 cites W2128793357 @default.
• W2136060128 cites W2129389823 @default.
• W2136060128 cites W2133110080 @default.
• W2136060128 cites W2136426653 @default.
• W2136060128 cites W2150382709 @default.
• W2136060128 cites W2150752051 @default.
• W2136060128 cites W2152344953 @default.
• W2136060128 cites W2162658917 @default.
• W2136060128 cites W2593728425 @default.
• W2136060128 doi "https://doi.org/10.1124/jpet.111.188441" @default.
• W2136060128 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22040680" @default.
• W2136060128 hasPublicationYear "2011" @default.
• W2136060128 type Work @default.
• W2136060128 sameAs 2136060128 @default.
• W2136060128 citedByCount "99" @default.
• W2136060128 countsByYear W21360601282012 @default.
• W2136060128 countsByYear W21360601282013 @default.
• W2136060128 countsByYear W21360601282014 @default.
• W2136060128 countsByYear W21360601282015 @default.
• W2136060128 countsByYear W21360601282016 @default.
• W2136060128 countsByYear W21360601282017 @default.
• W2136060128 countsByYear W21360601282018 @default.
• W2136060128 countsByYear W21360601282019 @default.
• W2136060128 countsByYear W21360601282020 @default.
• W2136060128 countsByYear W21360601282021 @default.
• W2136060128 countsByYear W21360601282022 @default.
• W2136060128 countsByYear W21360601282023 @default.
• W2136060128 crossrefType "journal-article" @default.
• W2136060128 hasAuthorship W2136060128A5000641347 @default.
• W2136060128 hasAuthorship W2136060128A5013834732 @default.
• W2136060128 hasAuthorship W2136060128A5014527416 @default.
• W2136060128 hasAuthorship W2136060128A5017059863 @default.
• W2136060128 hasAuthorship W2136060128A5020422833 @default.
• W2136060128 hasAuthorship W2136060128A5020860588 @default.
• W2136060128 hasAuthorship W2136060128A5026142305 @default.
• W2136060128 hasAuthorship W2136060128A5028670333 @default.
• W2136060128 hasAuthorship W2136060128A5053159281 @default.
• W2136060128 hasAuthorship W2136060128A5063895679 @default.
• W2136060128 hasAuthorship W2136060128A5068917225 @default.
• W2136060128 hasAuthorship W2136060128A5080730505 @default.
• W2136060128 hasAuthorship W2136060128A5084300737 @default.
• W2136060128 hasConcept C184235292 @default.
• W2136060128 hasConcept C185592680 @default.
• W2136060128 hasConcept C203014093 @default.
• W2136060128 hasConcept C2777077863 @default.
• W2136060128 hasConcept C35174551 @default.
• W2136060128 hasConcept C42362537 @default.
• W2136060128 hasConcept C55493867 @default.
• W2136060128 hasConcept C62478195 @default.
• W2136060128 hasConcept C71924100 @default.
• W2136060128 hasConcept C8891405 @default.
• W2136060128 hasConcept C90059517 @default.
• W2136060128 hasConcept C98274493 @default.
• W2136060128 hasConceptScore W2136060128C184235292 @default.
• W2136060128 hasConceptScore W2136060128C185592680 @default.
• W2136060128 hasConceptScore W2136060128C203014093 @default.

• next