Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun 1;58(6):953-962.
doi: 10.1093/rheumatology/key339.

Clinical significance of Janus Kinase inhibitor selectivity

Ernest H Choy  1
Affiliations
Review

Clinical significance of Janus Kinase inhibitor selectivity

Ernest H Choy. Rheumatology (Oxford). .

Erratum in

Abstract

Cytokines are key drivers of inflammation in RA, and anti-cytokine therapy has improved the outcome of RA. Janus Kinases (JAK) are intracellular tyrosine kinases linked to intracellular domains of many cytokine receptors. There are four JAK isoforms: JAK1, JAK2, JAK3 and TYK2. Different cytokine receptor families utilize specific JAK isoforms for signal transduction. Phosphorylation of JAK when cytokine binds to its cognate receptor leads to phosphorylation of other intracellular molecules that eventually leads to gene transcription. Oral JAK inhibitors (JAKi) have been developed as anti-cytokine therapy in RA. Two JAKi, tofacitinib and baricitinib, have been approved recently for the treatment of RA, and many JAKi are currently in development. JAKi inhibit JAK isoforms with different selectivity. This review discusses the efficacy and safety of JAKi in RA, in particular the potential clinical significance of JAKi selectivity.

Keywords: DMARDs; Janus Kinase; rheumatoid arthritis; targeted synthetic DMARDs; treatment.

PubMed Disclaimer

Figures

<sc>Fig</sc>. 1
Fig. 1
Cytokine signalling via JAK isoforms and their inhibitors JAK: Janus Kinase; p: phosphate.
See this image and copyright information in PMC

References

    1. Yamaoka K, Saharinen P, Pesu M. et al. The Janus kinases (Jaks). Genome Biol 2004;5:253. - PMC - PubMed
    1. Dayer JM, Choy E.. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford) 2010;49:15–24. - PMC - PubMed
    1. Rawlings JS, Rosler KM, Harrison DA.. The JAK/STAT signaling pathway. J Cell Sci 2004;117:1281–3. - PubMed
    1. Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM.. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs 2017;77:521–46. - PMC - PubMed
    1. Rodig SJ, Meraz MA, White JM.. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell 1998;93:373–83. - PubMed

Publication types

MeSH terms