title: Therapeutic potential of tyrosine kinase 2 in autoimmunity.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Anhui Medical University, School of Public Health, Department of Epidemiology and Biostatistics , 81 Meishan Road, Hefei, Anhui, 230032 , PR China +86 551 65167726 ; +86 551 65161171 ; ydq@ahmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Yang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Liu
authors.forename: Wang-Dong
authors.initials: WD
authors.lastname: Xu
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Pan
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Ye
mesh_terms: D056704:Adaptive Immunity; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000201:enzymology; D015551:Autoimmunity / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D015195:Drug Design; D020022:Genetic Predisposition to Disease; D006801:Humans; D007111:Immunity, Cellular; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D058990:Molecular Targeted Therapy; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053634:TYK2 Kinase; C070139:TYK2 protein, human