title: A p38 mitogen-activated protein kinase inhibitor screening method using growth recovery of Escherichia coli as an index.
abstract: The p38 mitogen-activated protein (MAP) kinase is the central signaling molecule regulating the cellular response to a multitude of external stimuli. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of some diseases, especially where aberrant cytokine signaling is the driver of disease. Here we established a simple inhibitor screening method for a human protein by using bacteria in combination with the growth recovery as an index. The screening successfully identified benzyl coumarin derivatives as p38 inhibitors. These compounds not only rescue growth retardation of p38-transformed bacteria but also inhibit p38 activity in vitro and in human cells. This study demonstrates that this is a promising and economical inhibitor screening method not only for p38 but also for other proteins.
authors.affiliation: Antibiotics Laboratory and Bioarchitect Research Group, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Kawai
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Sudo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D015153:Blotting, Western; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004926:Escherichia coli / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D003374:Coumarins; D047428:Protein Kinase Inhibitors; C030123:coumarin; D048051:p38 Mitogen-Activated Protein Kinases