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.
Keywords: Jak kinase, crystal structure, CP-690, 550, Jak2-V617F, kinase inhibitor, drug, cytokine signaling, mutation, translocation, STAT
Current Drug Targets
Title: The Use of Structural Biology in Janus Kinase Targeted Drug Discovery
Volume: 12 Issue: 4
Author(s): Nilda L. Alicea-Velazquez and Titus J. Boggon
Affiliation:
Keywords: Jak kinase, crystal structure, CP-690, 550, Jak2-V617F, kinase inhibitor, drug, cytokine signaling, mutation, translocation, STAT
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.
Export Options
About this article
Cite this article as:
L. Alicea-Velazquez Nilda and J. Boggon Titus, The Use of Structural Biology in Janus Kinase Targeted Drug Discovery, Current Drug Targets 2011; 12 (4) . https://dx.doi.org/10.2174/138945011794751528
DOI https://dx.doi.org/10.2174/138945011794751528 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Metaboloepigenetics: The Emerging Network in Stem Cell Homeostasis Regulation
Current Stem Cell Research & Therapy Advanced Assessment of the Endogenous Hormone Level as a Potential Biomarker of the Urogenital Tract Cancer
Combinatorial Chemistry & High Throughput Screening Treatment of Acute Leukaemias with Monoclonal Antibodies: Current Status and Future Prospects
Cardiovascular & Hematological Agents in Medicinal Chemistry Doxsaliform: A Novel N-Mannich Base Prodrug of a Doxorubicin Formaldehyde Conjugate
Letters in Drug Design & Discovery Purine Analogues as Kinase Inhibitors: A Review
Recent Patents on Anti-Cancer Drug Discovery Cancer Stem-Cells Patents in the Context of their Therapeutic Purposes: Exploring the Latest Trends (2011-2015)
Recent Patents on Regenerative Medicine PI3K/AKT/mTOR Inhibitors In Ovarian Cancer
Current Medicinal Chemistry Naturally Occuring Pyrrolo[1,4]benzodiazepines in Bacteria
Mini-Reviews in Organic Chemistry Recent Advance in the Research of Flavonoids as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Application of Stem Cell Therapy During the Treatment of HIV/AIDS and Duchenne Muscular Dystrophy
Current Stem Cell Research & Therapy Cutoff Values of D-Dimer and FDP in Plasma for the Diagnosis of Thrombosis
Vascular Disease Prevention (Discontinued) Molecular Foundations for Personalized Therapy in Prostate Cancer
Current Drug Targets Characterization of the Lymphotropic Amplicons-6 and Tamplicon-7 Vectors Derived from HHV-6 and HHV-7
Current Gene Therapy Stem Cells: In Sickness and in Health
Current Stem Cell Research & Therapy Prospective Teratology of Retinoic Acid Metabolic Blocking Agents (RAMBAs) and Loss of CYP26 Activity
Current Pharmaceutical Design The Application of Single Nucleotide Polymorphism Microarrays in Cancer Research
Current Genomics Editorial (Thematic Issue: Unlocking the Potential of Stem Cells in Cell Therapy, Drug Delivery and Drug Discovery)
Current Drug Delivery Cytosine Methyltransferases as Tumor Markers
Current Genomics Novel Lipid and Polymeric Materials as Delivery Systems for Nucleic Acid Based Drugs
Current Drug Metabolism BCR-ABL Inhibitors in Chronic Myeloid Leukemia: Process Chemistry and Biochemical Profile
Current Medicinal Chemistry