title: Targeting JAK3 in kidney transplantation:  current status and future options.
abstract: OBJECTIVE
  This review will discuss the mechanism of action and important clinical trial data in renal transplantation for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib.
  
  
  RESULTS
  JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, particularly members of the cytokine receptor common gamma (cγ) chain family. JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated efficacy in autoimmune disorders such as psoriasis and rheumatoid arthritis. Nonhuman primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared with vehicle control. Renal transplant clinical trials in humans have demonstrated tofacitinib to be noninferior to cyclosporine in terms of rejection rates and graft survival. There was also a lower rate of new-onset diabetes after transplant. However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis.
  
  
  CONCLUSIONS
  Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.
authors.affiliation: University of California, San Francisco, Kidney Transplant Service, San Francisco, California 94143-0780, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wojciechowski
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
mesh_terms: D006084:Graft Rejection / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D058990:Molecular Targeted Therapy; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; C507933:JAK3 protein, human; D053616:Janus Kinase 3