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). 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. Tofacitinib prevents rejection and prolongs survival in murine and cynomolgus monkey models of heterotopic heart and kidney transplantation, respectively. Formulations containing tofacitinib have been...