Drugs in R & D

, Volume 9, Issue 6, pp 397–434

New Approaches to the Treatment of Inflammatory Disease

Focus on Small-Molecule Inhibitors of Signal Transduction Pathways
Review Article

DOI: 10.2165/0126839-200809060-00005

Cite this article as:
Ivanenkov, Y.A., Balakin, K.V. & Tkachenko, S.E. Drugs in R D (2008) 9: 397. doi:10.2165/0126839-200809060-00005

Abstract

This‘state-of-the-art’ review specifically focuses on alternative signalling pathways deeply involved in acute and chronic inflammatory responses initiated by various pathological stimuli. The accumulated scientific knowledge has already revealed key biological targets, such as COX-2, and related proinflammatory mediators (cytokines and chemokines, interleukins [ILs], tumour necrosis factor [TNF]-α, migration inhibition factor [MIF], interferon [IFN]-ψ and matrix metalloproteinases [MMPs]) implicated in uncontrolled, destructive inflammatory reaction. A number of physiologically active agents are currently approved for market or are under active investigation in different clinical trials. However, recent findings have exposed the fatal adverse effects directly associated with drug therapy based on COX-2 inhibition. Given these possible harmful outcomes, a range of novel therapeutically relevant biological targets that include nuclear transcription factor (NF-κB), p38 mitogen-activated protein kinases (MAPK) and Janus protein tyrosine kinases and signal transducers and activators of transcription (JAK/STAT) signalling pathways has received growing attention. Here we discuss recent progress in the identification and development of novel, clinically approved or evaluated small-molecule regulators of these signalling cascades as promising anti-inflammatory drugs.

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.ChemDiv, Inc.San DiegoUSA
  2. 2.Institute of Physiologically Active CompoundsRussian Academy of SciencesChernogolovka, Moscow reg.Russia
  3. 3.Chemical Diversity Research Institute (IIHR)Khimki, Moscow reg.Russia

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