title: Selective JAK inhibitors in development for rheumatoid arthritis.
abstract: BACKGROUND
  The JAK kinases are a family of four tyrosine receptor kinases that play a pivotal role in cytokine receptor signalling pathways via their interaction with signal transducers and activators of transcription proteins. Selective inhibitors of JAK kinases are viewed as of considerable potential as disease-modifying anti-inflammatory drugs for the treatment of rheumatoid arthritis.
  
  
  METHODS
  This article provides a review of the clinical development and available clinical results for those JAK inhibitors currently under investigation. Phase II data for four JAK inhibitors (baricitinib, decernotinib, filgotinib and INCB-039110) are contrasted with that reported for the recently approved JAK inhibitor tofacitinib. The preclinical data on these, in addition to peficitinib, ABT-494, INCB-047986 and AC-410 are also discussed, as are some of the inhibitors in preclinical development.
  
  
  CONCLUSIONS
  JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily. JAK inhibitors differ in isoform specificity profiles, with good efficacy achievable by selective inhibition of either JAK1 (filgotinib or INCB-039110) or JAK3 (decernotinib). It remains to be seen what selectivity provides the optimal side-effect profile and to what extent inhibition of JAK2 should be avoided.
authors.affiliation: Norman Consulting , 18 Pink Lane, Burnham, Bucks, SL1 8JW , UK peter.norman2@btinternet.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Norman
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology; D015195:Drug Design; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D047428:Protein Kinase Inhibitors; D053612:Janus Kinases
keywords: JAK1 inhibitor; JAK3 inhibitor; baricitinib; decernotinib; filgotinib; peficitinib; rheumatoid arthritis; tofacitinib