Pharmacological inhibitors of MAPK pathways

Trends Pharmacol Sci. 2002 Jan;23(1):40-5. doi: 10.1016/s0165-6147(00)01865-4.


Mitogen-activated protein kinases [MAPKs, also called extracellular signal-regulated kinases (ERKs)] are constituents of numerous signal transduction pathways, and are activated by protein kinase cascades. Intense efforts are under way to develop and evaluate compounds that target components of MAPK pathways. In this article, the current status of inhibitors of MAPK pathways will be presented with a focus on the properties of small-molecule inhibitors of p38, MEK1 and MEK2 protein kinases. Several of these inhibitors are effective in animal models of disease and have advanced to clinical trials for the treatment of inflammatory diseases and cancer. The clinical utility of specifically targeting a subset of cellular signaling cascades and signaling cascades that regulate pleiotropic cellular processes are being evaluated. The results of these efforts have broad implications for the treatment of many diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Design
  • Drugs, Investigational
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • MAP Kinase Signaling System / drug effects*
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Proto-Oncogene Proteins c-raf / antagonists & inhibitors
  • Substrate Specificity
  • p38 Mitogen-Activated Protein Kinases


  • Drugs, Investigational
  • Enzyme Inhibitors
  • MAP2K2 protein, human
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases