The p38 MAPK Inhibitors for the Treatment of Inflammatory Diseases and Cancer

Expert Opin Investig Drugs. 2009 Dec;18(12):1893-905. doi: 10.1517/13543780903321490.

Abstract

Background: The p38 mitogen-activated protein kinase (MAPK) is activated by various pro-inflammatory and stressful stimuli. Mounting evidence suggests that the p38 MAPK signaling cascade is involved in various biological responses other than inflammation such as cell proliferation, differentiation, apoptosis and invasion, suggesting that the p38 MAPK can serve as a potential therapeutic target for the treatment of not only inflammatory diseases but also cancer.

Methods: The unique characteristics of p38 MAPK are summarized with regard to activation and function of p38 MAPK signaling cascades. We then discuss the involvement of p38 MAPK in diseases and the implications of the possible therapeutic use of p38 MAPK inhibitors. The p38 MAPK inhibitors that have been used in the in vitro/in vivo systems as well as in the clinical trials are summarized.

Results/conclusion: The p38 MAPK plays an important role in key cellular processes related to inflammation and cancer. Understanding the signal transduction mechanisms and gene regulation by p38 MAPK provides useful information in the development of p38 MAPK inhibitors with therapeutic benefits with reduced side effects. In this review, we summarize and present the list of p38 MAPK inhibitors in in vitro/in vivo studies as well as in clinical trials.

Publication types

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

MeSH terms

  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • MAP Kinase Signaling System / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / therapeutic use*

Substances

  • Drugs, Investigational
  • Enzyme Inhibitors
  • p38 Mitogen-Activated Protein Kinases