title: p38α mitogen-activated protein kinase inhibitors, a patent review (2005-2011).
abstract: BACKGROUND
  Since the first biological factor that neutralized tumor necrosis (TNF)-α was brought to the market, there has been a desperate search for small molecules with the same efficacy in therapy of inflammatory disorders. One of the most promising targets is p38α mitogen-activated protein (MAP) kinase. This enzyme is a key player in a vast number of inflammatory and autoimmune processes.
  
  
  METHODS
  Almost every international company doing research in drug discovery is or was involved in the development of compounds that inhibit p38α MAP kinase. Herein their patents and the corresponding publications are summarized.
  
  
  CONCLUSIONS
  In the last few years, compounds have become more potent and more selective, for example, by induction of the so-called glycine flip. Furthermore, some companies are striving for selectivity with respect to isoforms. The increasing availability of rapid screening services, which include more than 400 kinases, has encouraged companies to reconsider traditional approaches. The most promising approach appears to be the development of linear binding molecules that feature a carbonyl oxygen that can enforce the glycine flip. Furthermore, recent projects increasingly target new fields of application, for example, pulmonary diseases. This might be the most important trend of the past few years.
authors.affiliation: University of Tuebingen, Institute of Pharmacy, Auf der Morgenstelle 8, D-72076 Tuebingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
authors.forename: Solveigh C
authors.initials: SC
authors.lastname: Koeberle
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Laufer
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D047428:Protein Kinase Inhibitors; D048308:Mitogen-Activated Protein Kinase 14