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Therapeutic potential of tyrosine kinase 2 in autoimmunity.
- Source :
-
Expert opinion on therapeutic targets [Expert Opin Ther Targets] 2014 May; Vol. 18 (5), pp. 571-80. Date of Electronic Publication: 2014 Mar 21. - Publication Year :
- 2014
-
Abstract
- Introduction: Tyrosine kinase 2 (Tyk2) is a Janus kinase family member that is crucial for signaling transduction in response to a wide variety of cytokines, including type I IFNs, IL-6, IL-10, IL-12 and IL-23. An appropriate expression of Tyk2-mediated signaling might be essential for maintaining normal immune responses.<br />Areas Covered: This review summarizes that Tyk2 is essential for the differentiation and function of a wide variety of immune cells, including natural killer cells, B cells, as well as T helper cells. In addition, Tyk2-mediated signaling promoted the production of autoimmune-associated components, which is implicated in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis. Aberrant expression of Tyk2 was observed in many autoimmune conditions.<br />Expert Opinion: Until recently, no patent filings had claimed selective inhibitors of Tyk2. Both CP-690,500 and CMP6 failed to be used in clinical treatment due to the difficulties of finding suitable selective leads or due to detrimental toxicities. Although the result of Cmpd1 is promising, it remains to be seen how specific the Tyk2 inhibitor is and how they are working. Currently, structure-based drug design (SBDD) technology has provided us with a quite useful window for SBDD of Tyk2 inhibitors.
- Subjects :
- Adaptive Immunity
Autoimmune Diseases enzymology
Dendritic Cells drug effects
Dendritic Cells enzymology
Dendritic Cells immunology
Drug Design
Genetic Predisposition to Disease
Humans
Immunity, Cellular
Lymphocyte Subsets drug effects
Lymphocyte Subsets enzymology
Lymphocyte Subsets immunology
Macrophages drug effects
Macrophages enzymology
Macrophages immunology
Neutrophils drug effects
Neutrophils enzymology
Neutrophils immunology
Piperidines adverse effects
Piperidines therapeutic use
Protein Kinase Inhibitors pharmacology
Pyrimidines adverse effects
Pyrimidines therapeutic use
Pyrroles adverse effects
Pyrroles therapeutic use
TYK2 Kinase genetics
TYK2 Kinase physiology
Autoimmune Diseases drug therapy
Autoimmunity physiology
Molecular Targeted Therapy
Protein Kinase Inhibitors therapeutic use
TYK2 Kinase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1744-7631
- Volume :
- 18
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Expert opinion on therapeutic targets
- Publication Type :
- Academic Journal
- Accession number :
- 24654603
- Full Text :
- https://doi.org/10.1517/14728222.2014.892925