Pfizer's JAK inhibitor sails through phase 3 in rheumatoid arthritis

467 JAK inhibitors like tofacitinib tread a fine line between therapeutic down-modulation of autoimmunity and outright immunosuppression. (Tofacitinib was first conceived as an immunosuppressant for use in organ transplantation.) The four members of the JAK family—JAKs 1, 2 and 3, and TYK2—play a crucial role in immunity by enabling cytokines, secreted proteins that help orchestrate the immune response, to signal through their receptors. Roughly 60 cytokines signal through type I and type II cytokine receptors, which have no catalytic kinase activity of their own. These receptors instead rely on JAK kinases for receptor phosphorylation, which creates a docking site for STAT transcription factors. Knocking out Jak1 and Jak2 in mice results in perinatal and embryonic lethality, respectively, and Jak3 knockouts have severe combined immunodeficiency. Pfizer’s JAK inhibitor sails through phase 3 in rheumatoid arthritis