Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease

Cytokines are critical for normal cell growth and immunoregulation but also contribute to growth of malignant cells and drive immune-mediated disease. A large subset of immunoregulatory cytokines uses the type I and type II cytokine receptors and pharmacological targeting of these cytokines/cytokines receptors has proven to be efficacious in treating immune and inflammatory diseases. These receptors rely on Janus family of kinases (Jaks) for signal transduction. Recently the first Jak inhibitor (jakinib) has been approved by the FDA and a second has been recommended for approval. Many other Jakinibs are likely to follow and in this brief review, we will discuss the state-of-the art of this new class of pharmacological agents.

► Cytokines are critical contributors to autoimmune disease, cancer, and other diseases. ► Janus kinases (Jaks) selectively associate with type I and II cytokine receptors. ► Jaks have essential, nonredundant roles in mediating signals via these receptors. ► Ruxolitinib is approved for treatment of myelofibrosis, a disorder associated with Jak2 mutations. ► Tofacitinib has shown efficacy in trials in rheumatoid arthritis and other autoimmune diseases.