Skepinone-L is a selective p38 mitogen-activated protein kinase inhibitor

Nat Chem Biol. 2011 Dec 25;8(2):141-3. doi: 10.1038/nchembio.761.


Until now, a lack of inhibitors with high potency and selectivity in vivo has hampered investigation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. We describe the design of skepinone-L, which is, to our knowledge, the first ATP-competitive p38 MAPK inhibitor with excellent in vivo efficacy and selectivity. Therefore, skepinone-L is a valuable probe for chemical biology research, and it may foster the development of a unique class of kinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate
  • Animals
  • Binding, Competitive
  • Dibenzocycloheptenes / chemistry*
  • Drug Design
  • Mice
  • Models, Molecular
  • Protein Interaction Domains and Motifs
  • Protein Kinase Inhibitors / chemistry*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*


  • Dibenzocycloheptenes
  • Protein Kinase Inhibitors
  • skepinone-L
  • Adenosine Triphosphate
  • p38 Mitogen-Activated Protein Kinases

Associated data

  • PDB/3QUE
  • PDB/3ZYA
  • PubChem-Substance/131287876
  • PubChem-Substance/131287877
  • PubChem-Substance/131287878
  • PubChem-Substance/131287879
  • PubChem-Substance/131287880
  • PubChem-Substance/131287881
  • PubChem-Substance/131287882
  • PubChem-Substance/131287883
  • PubChem-Substance/131287884
  • PubChem-Substance/131287885
  • PubChem-Substance/131287886
  • PubChem-Substance/131287887
  • PubChem-Substance/131287888