title: p38 MAPK inhibitors: a patent review (2012 - 2013).
abstract: BACKGROUND
  The p38 MAPK is a ubiquitous target in the research-based pharmaceutical industry. It plays a decisive role in the regulation of the production of proinflammatory cytokines. Since novel biological therapies have revolutionized the treatment of chronic inflammatory diseases, an intensive global search is underway for small molecules for the same application.
  
  
  METHODS
  Herein, the patents and the corresponding publications of international companies, which focus on the development and identification of a new generation of small-molecule p38 inhibitors, are summarized.
  
  
  CONCLUSIONS
  The most promising approach is the development of linear binders, which induce a glycine flip at Gly110 of the kinase hinge region by a carbonyl oxygen atom of the respective ligand. The major focus of the patent works was the application of molecules in new indications. Previous applications were in the treatment of rheumatoid arthritis; currently, there are several new applications, including pulmonary diseases, cancer and Alzheimer's disease. Targeting p38 upstream kinases and downstream effectors has also proved to be a very promising step in the development of more effective inhibitors. A further trend is drug combination, applied to a wide range of indications, such as chronic obstructive pulmonary disease and cancer.
authors.affiliation: Eberhard-Karls-University Tübingen, Department of Pharmaceutical/Medicinal Chemistry , Auf der Morgenstelle 8, 72076 Tübingen , Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bühler
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Laufer
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004345:Drug Industry; D006801:Humans; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases