JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.

Abstract

The discovery of cytokines as key drivers of immune-mediated diseases has spurred efforts to target their associated signalling pathways. Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines, and small-molecule inhibitors of JAKs (jakinibs) have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. Building on the clinical success of first-generation jakinibs, second-generation compounds that claim to be more selective are currently undergoing development and proceeding to clinical trials. However, important questions remain about the advantages and limitations of improved JAK selectivity, optimal routes and dosing regimens and how best to identify patients who will benefit from jakinibs. This Review discusses the biology of jakinibs from a translational perspective, focusing on recent insights from clinical trials, the development of novel agents and the use of jakinibs in a spectrum of immune and inflammatory diseases.

• Authors: Daniella M Schwartz, Yuka Kanno, Alejandro Villarino, Michael Ward, Massimo Gadina, John J O'Shea
• Journal: Nature reviews. Drug discovery (Nat Rev Drug Discov) Vol. 16 Issue 12 Pg. 843-862 (Dec 2017) ISSN: 1474-1784 [Electronic] England
• PMID: 29104284 (Publication Type: Journal Article, Review)

Chemical References

• Cytokines
• Janus Kinase Inhibitors
• Janus Kinases

Topics

• Animals
• Cytokines (immunology)
• Drug Design
• Humans
• Immune System Diseases (drug therapy, physiopathology)
• Inflammation (drug therapy, physiopathology)
• Janus Kinase Inhibitors (adverse effects, pharmacology, therapeutic use)
• Janus Kinases (drug effects, metabolism)
• Signal Transduction (drug effects)