Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site

• Published in: The Journal of biological chemistry Vol. 272; no. 18; pp. 12116 - 12121
• Main Authors: Young, P R, McLaughlin, M M, Kumar, S, Kassis, S, Doyle, M L, McNulty, D, Gallagher, T F, Fisher, S, McDonnell, P C, Carr, S A, Huddleston, M J, Seibel, G, Porter, T G, Livi, G P, Adams, J L, Lee, J C
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 02.05.1997
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine Triphosphate - metabolism; Affinity Labels; Amino Acid Sequence; Binding Sites; Binding, Competitive; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases - chemistry; Calcium-Calmodulin-Dependent Protein Kinases - isolation & purification; Calorimetry; Cloning, Molecular; Cross-Linking Reagents; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Escherichia coli; HeLa Cells; Humans; Imidazoles - metabolism; Imidazoles - pharmacology; Kinetics; Mitogen-Activated Protein Kinases; Mutagenesis, Site-Directed; p38 Mitogen-Activated Protein Kinases; Pyridines - metabolism; Pyridines - pharmacology; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - chemistry; Recombinant Proteins - isolation & purification; Saccharomyces cerevisiae

The site of action of a series of pyridinyl imidazole compounds that are selective inhibitors of p38 mitogen-activated protein kinase in vitro and block proinflammatory cytokine production in vivo has been determined. Using Edman sequencing, 125 I-SB206718 was shown to cross-link to the nonphosphory...