JAK inhibition as a therapeutic strategy for immune and inflammatory diseases

Daniella M. Schwartz, Yuka Kanno, Alejandro Villarino, Michael Ward, Massimo Gadina, John J. O'Shea

Research output: Contribution to journalReview articlepeer-review

344 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)843-862
Number of pages20
JournalNature Reviews Drug Discovery
Volume16
Issue number12
DOIs
StatePublished - Nov 28 2017
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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