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Discovery and Development of Janus Kinase (JAK) Inhibitors for Inflammatory Diseases

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Pfizer Immunosciences, 200 CambridgePark, Cambridge, Massachusetts 02140, United States
Center for Chemistry Innovation and Excellence, Pfizer, Inc., Eastern Point Road, Groton, Connecticut 06340, United States
*Telephone: 860-441-0205. E-mail: [email protected]
Cite this: J. Med. Chem. 2014, 57, 12, 5023–5038
Publication Date (Web):January 13, 2014
https://doi.org/10.1021/jm401490p
Copyright © 2014 American Chemical Society
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Abstract

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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.

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