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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Anti-Inflammatory Agents / chemistry*
-
Anti-Inflammatory Agents / pharmacology
-
Antirheumatic Agents / pharmacology
-
Antirheumatic Agents / therapeutic use
-
Autoimmune Diseases / drug therapy*
-
Autoimmune Diseases / immunology
-
Autoimmune Diseases / metabolism
-
Clinical Trials as Topic
-
Cytokines / metabolism
-
Humans
-
Inflammation / drug therapy*
-
Inflammation / immunology
-
Inflammation / metabolism
-
Inflammatory Bowel Diseases / drug therapy
-
Inflammatory Bowel Diseases / immunology
-
Inflammatory Bowel Diseases / metabolism
-
Janus Kinases / antagonists & inhibitors*
-
Janus Kinases / chemistry
-
Janus Kinases / metabolism
-
Piperidines / pharmacology
-
Piperidines / therapeutic use
-
Protein Conformation
-
Protein Kinase Inhibitors / chemistry*
-
Protein Kinase Inhibitors / pharmacology
-
Pyrimidines / pharmacology
-
Pyrimidines / therapeutic use
-
Pyrroles / pharmacology
-
Pyrroles / therapeutic use
-
Signal Transduction
Substances
-
Anti-Inflammatory Agents
-
Antirheumatic Agents
-
Cytokines
-
Piperidines
-
Protein Kinase Inhibitors
-
Pyrimidines
-
Pyrroles
-
tofacitinib
-
Janus Kinases