Novel small molecule therapeutics in rheumatoid arthritis

Rheumatology (Oxford). 2013 Jul;52(7):1155-62. doi: 10.1093/rheumatology/kes367. Epub 2013 Jan 7.

Abstract

A new wave of emerging therapies for the treatment of autoimmune and inflammatory diseases is under development. These therapies interrupt intracellular signalling through kinase inhibition. By interrupting one or more kinases it is possible to modulate the function of cellular structures such as surface receptors, signalling proteins and transcription of nuclear proteins and thus influence the behaviour of the cell types targeted. With these advances comes the significant potential to develop highly effective orally bioavailable therapeutics. The targets generating the greatest enthusiasm at this time for the treatment of autoimmune and inflammatory diseases include Janus-associated kinase, spleen tyrosine kinase, phosphodiesterase-4, Bruton's tyrosine kinase and phosphatidylinositol-3 kinase. Ultimately human trials will help us understand the potential risks and benefits of these novel approaches across a number of diseases.

Keywords: BTK; DMARDs; JAK; PDE4; PI3K; SYK; kinase; rheumatoid arthritis; small molecules; treatment.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Arthritis, Rheumatoid / drug therapy*
  • Class II Phosphatidylinositol 3-Kinases
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Janus Kinases / antagonists & inhibitors
  • Phosphodiesterase 4 Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Syk Kinase

Substances

  • Intracellular Signaling Peptides and Proteins
  • Phosphodiesterase 4 Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Class II Phosphatidylinositol 3-Kinases
  • PIK3C2B protein, human
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Janus Kinases
  • SYK protein, human
  • Syk Kinase