Current status of inflammasome blockers as anti-inflammatory drugs

Expert Opin Investig Drugs. 2012 Jul;21(7):995-1007. doi: 10.1517/13543784.2012.690032. Epub 2012 May 22.

Abstract

Introduction: The inflammasomes have emerged as key mediators of inflammation and immunity, yet clinical application of this knowledge has been limited by a lack of specific and drug-like antagonists. Recent studies using inflammasome knockout mice have shown that different inflammasomes control immunity in different pathologies. Drug-like antagonists acting up- or down-stream of the inflammasome pathway have been successfully used in clinics as important therapeutics to treat different inflammatory diseases.

Areas covered: The current literature has been reviewed on the role of inflammasomes in inflammatory disease, focusing on potential therapeutic applications of selective inflammasome antagonists as anti-inflammatory agents. Particular emphasis has been placed on the potential role of the different inflammasomes in common inflammatory diseases. The latest clinical developments for drugs targeting inflammasome pathways are covered.

Expert opinion: Recent studies using inflammasome knockout mice suggest its importance as a potential therapeutic target for the treatment of inflammatory disease. However, efficacious antagonists for the inflammasome for use in clinical studies are still at an early stage of development. Developing selective inflammasome antagonists is a challenge that if met, offers promise for the treatment of chronic inflammatory diseases. Major developments in this area will include the identification of reliable high-throughput screening methods for compounds directly targeting inflammasome assembly.

Publication types

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

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Caspase 1 / metabolism
  • Clinical Trials as Topic
  • Drug Discovery*
  • Humans
  • Immunity, Innate / drug effects
  • Inflammasomes / antagonists & inhibitors*
  • Inflammasomes / genetics
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Inflammation / immunology
  • Receptors, Purinergic P2X7 / metabolism
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Receptors, Purinergic P2X7
  • Caspase 1