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Open AccessJournal ArticleDOI

JAK inhibitors in dermatology: The promise of a new drug class

William Damsky, +1 more
- 01 Apr 2017 - 
- Vol. 76, Iss: 4, pp 736-744
TLDR
Evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions, and JAK inhibitors can be administered orally or used topically and represent a promising new class of medications.
Abstract
New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase–signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

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Citations
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Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis.

TL;DR: This review summarizes the current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.
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Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

TL;DR: This review summarises the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricit inib, ruxolitinIB, peficitinib) and second-generation selective JAK inhibitor(s) (decernotinib, filgotin ib, upadacit inib).
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Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19.

TL;DR: The possibilities and challenges of targeting the pathway in COVID-19 are reviewed, and JAK inhibition presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in CO VID-19.
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Jak Stat signaling and cancer: Opportunities, benefits and side effects of targeted inhibition.

TL;DR: The direct and mediated mechanisms of Jak stat signaling in and on tumors cells, the interactions with other signaling pathways and transcription factors and the targeting of the functionally crucial secondary modifications of Stat molecules suggest novel approaches to the future development of Jak Stat based cancer therapeutics.
References
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Journal ArticleDOI

The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention*

TL;DR: The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules.
Journal ArticleDOI

Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).

TL;DR: Two unrelated T- B+SCID patients who have homozygous mutations in the gene for Jak-3 are investigated and abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.
Journal ArticleDOI

Mutation of Jak3 in a Patient with SCID: Essential Role of Jak3 in Lymphoid Development

TL;DR: Observations indicate that the functions of γc are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling.
Journal ArticleDOI

Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition

TL;DR: It is shown that cytotoxic CD8+NKG2D+ T cells are both necessary and sufficient for the induction of AA in mouse models of disease, suggesting the potential clinical utility of JAK inhibition in human AA.
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