title: A protein kinase involved in the regulation of inflammatory cytokine biosynthesis.
abstract: Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.
authors.affiliation: Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
authors.forename: J T
authors.initials: JT
authors.lastname: Laydon
authors.forename: P C
authors.initials: PC
authors.lastname: McDonnell
authors.forename: T F
authors.initials: TF
authors.lastname: Gallagher
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: D
authors.initials: D
authors.lastname: Green
authors.forename: D
authors.initials: D
authors.lastname: McNulty
authors.forename: M J
authors.initials: MJ
authors.lastname: Blumenthal
authors.forename: J R
authors.initials: JR
authors.lastname: Heys
authors.forename: S W
authors.initials: SW
authors.lastname: Landvatter
authors.forename: J E
authors.initials: JE
authors.lastname: Strickler
authors.forename: M M
authors.initials: MM
authors.lastname: McLaughlin
authors.forename: I R
authors.initials: IR
authors.lastname: Siemens
authors.forename: S M
authors.initials: SM
authors.lastname: Fisher
authors.forename: G P
authors.initials: GP
authors.lastname: Livi
authors.forename: J R
authors.initials: JR
authors.lastname: White
authors.forename: J L
authors.initials: JL
authors.lastname: Adams
authors.forename: P R
authors.initials: PR
authors.lastname: Young
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018076:DNA, Complementary; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators; D007375:Interleukin-1 / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments; D011725:Pyridines / Q000494:pharmacology; D011869:Radioligand Assay; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D016207:Cytokines; D018076:DNA, Complementary; D007093:Imidazoles; D018836:Inflammation Mediators; D007375:Interleukin-1; D010446:Peptide Fragments; D011725:Pyridines; D011994:Recombinant Proteins; C090943:SB 206718; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole