However, even for a disorder like rheumatoid arthritis (RA) in which much progress has been made, most patients do not respond completely to currently available therapies, and there are relatively few examples of long-term remissions after cessation of therapy 2. Such therapies have dramatically altered outcomes for a range of diseases, including rheumatoid arthritis (RA), psoriasis and Inflammatory Bowel Disease (IBD) 1. The discovery of the numerous cytokines underlying the pathogenesis of allergic, inflammatory and autoimmune disorders has provided a basis for the development of highly successful therapeutic monoclonal antibodies and recombinant proteins that target several such cytokines and their receptors 1. This review will discuss the biology of jakinibs from a translational perspective, focusing on recent insights from clinical trials, the development of novel agents, and the use of jakinibs in a spectrum of immune and inflammatory diseases. However, important questions remain about the advantages and limitations of improved JAK selectivity, optimal routes and dosing regimens, and how best to identify patients that will benefit from jakinibs. Building on the clinical success of first-generation jakinibs, second-generation compounds which claim greater selectivity are currently undergoing development and proceeding to clinical trials. Small-molecule drugs that inhibit Janus kinases (jakinibs), which are essential signaling mediators downstream of many pro-inflammatory cytokines, have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies like rheumatoid arthritis, psoriasis and inflammatory bowel disease. Proof provided by biological therapies that cytokines are truly key drivers of immune-mediated diseases has spurred effort in targeting their associated signaling pathways.
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