The JAK kinases: Not just another kinase drug discovery target

There are four members of the JAK family of protein tyrosine kinases (PTKs) in the human genome. Since their discovery in 1989, great strides have been made in the understanding of their role in normal intracellular signalling. Importantly, their roles in pathologies ranging from cancer to immune de...

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Bibliographic Details
Published in:Seminars in cell & developmental biology 2008-08, Vol.19 (4), p.319-328
Main Author: Wilks, Andrew F.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Cancer
Drug Discovery
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - metabolism
Humans
Isoenzymes - chemistry
Isoenzymes - classification
Isoenzymes - genetics
Isoenzymes - metabolism
JAK
Janus Kinases - chemistry
Janus Kinases - classification
Janus Kinases - genetics
Janus Kinases - metabolism
Kinase inhibitors
Models, Molecular
Molecular Sequence Data
Molecular Structure
Myeloproliferative disorders
Protein Conformation
Review
Sequence Alignment
Signal Transduction - physiology
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Summary:There are four members of the JAK family of protein tyrosine kinases (PTKs) in the human genome. Since their discovery in 1989, great strides have been made in the understanding of their role in normal intracellular signalling. Importantly, their roles in pathologies ranging from cancer to immune deficiencies have placed them front and centre as potential drug targets. The recent discovery of the role of activating mutations in the kinase-like domain (KLD) of JAK2 in the development of polycythemia rubra vera, and the elaboration of KLD mutation as a broader mechanism by which cells might become hyperproliferative has sparked enormous interest in the development of JAK selective drug candidates. I review herein the progress that has been made in the discovery of JAK-targeted inhibitors, and discuss the challenges that face the development of these drugs for use in the clinic.
ISSN:1084-9521
1096-3634
DOI:10.1016/j.semcdb.2008.07.020