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

被引：512

作者：

Clark, James D. ^{[1
]}

Flanagan, Mark E. ^{[2
]}

Telliez, Jean-Baptiste ^{[1
]}

机构：

[1] Pfizer Immunosci, Cambridge, MA 02140 USA

[2] Pfizer Inc, Ctr Chem Innovat & Excellence, Groton, CT 06340 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 12期

关键词：

MODIFYING ANTIRHEUMATIC DRUGS; STRUCTURE-BASED DESIGN; TYROSINE KINASE; PSEUDOKINASE DOMAIN; HIGH SELECTIVITY; PROTEIN-KINASE; RODENT MODELS; POTENT; ARTHRITIS; CP-690,550;

D O I：

10.1021/jm401490p

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：5023 / 5038

页数：16

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