title: Is there a future for small molecule drugs in the treatment of rheumatic diseases?
abstract: OBJECTIVE
  In this review, we outline the landscape of recent developments regarding small molecule compounds for the treatment of inflammatory disorders by discussing drug candidates currently in the pipeline. We also stress the fact that novel techniques are available to evaluate the safety of new therapeutics at an early stage of development.
  
  
  RESULTS
  Regulation of signal transduction has evolved into an important field of drug research, and small molecule inhibitors of a number of pathways are tested as new anti-inflammatory agents. For rheumatic diseases, specific Jak3 and Syk inhibitors are, so far, the most successful compounds due to their good efficacy, representing a significant advantage over p38 mitogen-activated protein kinase inhibitors. Additional benefit in the treatment of inflammatory diseases may be provided by targeting CD80, IL-12/IL-23, AP-1 transcription factor and receptors modulating cellular activation like chemokine receptors, Toll-like receptors and adenosine A3 receptor.
  
  
  CONCLUSIONS
  There is a big hope that novel small molecule drugs, which are rationally designed, based on scientific advancements and biotechnological improvements, will achieve or even exceed efficacy of protein drugs. Thereby, new therapeutic alternatives would be given, and chances for improved outcomes in the care of rheumatic patients provided.
authors.affiliation: Center of Experimental Rheumatology, University Hospital Zurich, Zurich Center of Integrative Human Physiology, University of Zurich, Switzerland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Stanczyk
authors.forename: Caroline
authors.initials: C
authors.lastname: Ospelt
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases