title: Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases.
abstract: The Janus kinases (JAKs) are a family of intracellular tyrosine kinases that play an essential role in the signaling of numerous cytokines that have been implicated in the pathogenesis of inflammatory diseases. As a consequence, the JAKs have received significant attention in recent years from the pharmaceutical and biotechnology industries as therapeutic targets. Here, we provide a review of the JAK pathways, the structure, function, and activation of the JAK enzymes followed by a detailed look at the JAK inhibitors currently in the clinic or approved for these indications. Finally, a perspective is provided on what the past decade of research with JAK inhibitors for inflammatory indications has taught along with thoughts on what the future may hold in terms of addressing the opportunities and challenges that remain.
authors.affiliation: Pfizer Immunosciences , 200 CambridgePark, Cambridge, Massachusetts 02140, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Clark
authors.forename: Mark E
authors.initials: ME
authors.lastname: Flanagan
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Telliez
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D016207:Cytokines; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053612:Janus Kinases