Tofacitinib (citrate)

Tofacitinib is a potent, cell-permeable inhibitor of all JAK isoforms (IC50s = 6.1, 12, and 8 nM for JAK1, JAK2, and JAK3, respectively).{22678} It is selective for JAK1-3 over ROCK2 and Lck (IC50s = 3,400 and 3,870 nM, respectively) as well as 28 additional kinases in enzyme assays (IC50s = >10,000 nM). It inhibits IL-2-mediated phosphorylation of JAK3 and STAT5 when used at a concentration of 30 ng/ml.{22675} Tofacitinib prevents rejection and prolongs survival in murine and cynomolgus monkey models of heterotopic heart and kidney transplantation, respectively. Formulations containing tofacitinib have been used in the prevention of organ allograft rejection as well as in the treatment of the inflammatory or autoimmune components of a host of diseases, including rheumatoid arthritis and ulcerative colitis.{22675,22677,22676,22679}