Tofacitinib citrate is a potent inhibitor of JAK3 (Janus kinase 3) with some JAK1 inhibitory activity as well. JAK3 blocks downstream STAT signaling resulting in potent inhibition of inflammatory cytokines with resultant immunosuppressive and anti-inflammatory activity.

Tofacitinib (formerly tasocitinib, CP-690550) is a drug being investigated by Pfizer for the treatment of rheumatoid arthritis (RA), psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection. It is an inhibitor of the enzyme Janus kinase 3 (JAK3), which means that it interferes with the JAK-STAT signaling pathway that transmits information outside the cell into the cell nucleus, influencing DNA transcription. Recently it has been shown in a murine model of established arthritis, tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue.

This efficacy in this disease model correlated with the inhibition of both JAK1 and 3 signaling pathways, suggesting that tofacitinib may exert therapeutic benefit via pathways that are not exclusive to inhibition of JAK3.

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