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Cited by 53Cytokine Signaling Pathways and InteractionsProtein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase Signaling

The use of structural biology in Janus kinase targeted drug discovery

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L. Alicea-Velazquez, Nilda, J. Boggon, Titus·2011·Current Drug Targets
DOI 10.2174/138945011794751528PMC PMC3786457
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Abstract

The Janus kinases (or Jak kinases) mediate cytokine and growth factor signal transduction. Acquired or inherited Jak mutations can result in dysregulation of Jak-mediated signal transduction and can be critical to disease acquisition in neoplasias including acute myeloid, acute lymphoblastic and acute megakaryoblastic leukemias, and in rare X-linked severe combined immunodeficiency. The discovery of an acquired Jak2 point mutation, V617F, in significant numbers of patients with classical myeloproliferative disorders has increased the interest in development of Jak2-specific tyrosine kinase inhibitors and consequently there are now over 20 publically available structures of Jak kinase domains that describe all four family members, Jak1, Jak2, Jak3, and Tyk2. Here we review the recent advances in understanding the druggable structure and function of the Jak family, with a focus on the structural biology of the Jak kinase domain. We will discuss how these advances impact the development of Jak-targeted therapeutics.

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Cited by

Sorted by citations

Authors
L. Alicea-Velazquez, N., & J. Boggon, T.
Venue
Current Drug Targets
Publisher
Bentham Science Publishers Ltd.
Published
2011-04-01
Volume
12
Issue
4
Pages
546-555
ISSN
1389-4501 (ISSN-L)
DOI
10.2174/138945011794751528
PMC
PMC3786457
OpenAlex
W2055150750
Cited by
53
References
1
Citations by year
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FWCI
2.68
Type
journal article
Language
en
Open access
Locations
  • Current Drug Targets (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI075133, R01 AI075133-S1)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
Janus kinase, tyrosine kinase inhibitors, JAK2 V617F mutation, myeloproliferative neoplasms, acute myeloid leukemia, X-linked severe combined immunodeficiency, cytokine signaling
MeSH terms
Animals, Humans, Mutation, Drug Design, Signal Transduction, Drug Delivery Systems, Protein Kinase Inhibitors, Janus Kinases, Drug Discovery

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