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Targeting protein kinases for the development of anti-inflammatory drugs

Philip Cohen1

  • 1The MRC Protein Phosphorylation Unit, University of Dundee, The Sir James Black Centre, Dundee, UK. p.cohen@dundee.ac.uk

Current Opinion in Cell Biology
|February 17, 2009
PubMed

Insights

Targeting protein kinases for chronic diseases is challenging. Alternative kinases like Tpl2, MAPKAP-K2/3, MSK1/2, IRAK4, and NIK show promise for inflammatory diseases and multiple myeloma.

Area of Science:

  • Immunology
  • Pharmacology
  • Oncology

Background:

  • Protein kinases are key drug targets, with 10 inhibitors approved for cancer treatment.
  • Developing safe, long-term protein kinase modulators for chronic diseases remains unresolved.
  • p38alpha MAPK inhibitors for rheumatoid arthritis and psoriasis faced side effects, halting Phase III trials.

Purpose of the Study:

  • To review challenges in targeting p38 MAPK for chronic inflammatory diseases.
  • To identify alternative protein kinase targets within the innate immune system.
  • To explore NIK as a potential target for multiple myeloma.

Main Methods:

  • Literature review of protein kinase inhibitors and clinical trial outcomes.
  • Analysis of protein kinases involved in innate immune system regulation.
  • Evaluation of therapeutic potential for chronic inflammatory conditions and malignancies.

Main Results:

  • p38alpha MAPK inhibition presents safety concerns for chronic use.
  • Tpl2, MAPKAP-K2/3, MSK1/2, and IRAK4 are identified as potential targets for inflammatory diseases.
  • NIK is highlighted as a promising target for multiple myeloma treatment.

Conclusions:

  • Alternative protein kinases offer safer and more effective therapeutic strategies for chronic inflammatory diseases.
  • NIK presents a novel target for addressing multiple myeloma, a B-cell malignancy.

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