Published online Sep 18, 2014. doi: 10.5312/wjo.v5.i4.496
Revised: June 5, 2014
Accepted: June 20, 2014
Published online: September 18, 2014
Core tip: Signal transduction is a regulator of gene expression in cells. Janus kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling is activated by pro-inflammatory cytokines which contributes to immune-mediated inflammation in rheumatoid arthritis. Medicinal chemistry was employed to develop JAK small molecule inhibitors for determining their clinical efficacy in active rheumatoid arthritis patients. Tofacitinib, a JAK small molecule inhibitor, is now generally used to treat moderate to severe rheumatoid arthritis patients who have not adequately responded to disease-modifying anti-rheumatic drugs or various biologic agents. The clinical efficacy of JAK small molecule inhibitors provides the impetus for future drug discovery targeted at other signal transduction pathways in rheumatoid arthritis.