50mg $120 In stock

Tofacitinib (CP-690550) is a potent, small molecule inhibitor of JAK-3, which exhibiting potent effects in preclinical transplantation and arthritis models. It displays greater antiproliferative and pro-apoptotic activity against murine multipotent factor-dependent cell Patersen-erythropoietin receptor (FDCP-EpoR) cells harboring JAK2(V617F) compared with JAK2(WT). JAK-3 has been shown to play a key role in cytokine signaling via gammac, e.g. IL-2, 4, 7, 9, 15, 21. In vitro, Tofacitinib effectively inhibited a murine mixed lymphocyte reaction (MLR) (IC50= 91 nm). Mice chronically dosed with CP-690550 (1.5-15 mg/kg/day) demonstrated dose- and time-dependent alterations in lymphocyte subsets when examined by flow cytometry. The most dramatic change observed was a 96% reduction in splenic NK1.1 + TCRbeta- cell numbers following 21 days of treatment. Delayed-type hypersensitivity (DTH) responses in sensitized mice were reduced in a dose-dependent manner following treatment with the JAK-3 inhibitor (1.87-30 mg/kg, s.c.). Extended survival of neonatal Balb/c hearts implanted into the ear pinna of MHC mismatched C3H/HEN mice was observed with CP-690550 monotherapy (10-30 mg/kg/day), but improved upon combination with cyclosporin (10 mg/kg/day). Furthermore, the ability of Tofacitinib to extend cardiac allograft survival in murine models suggests it may afford a new treatment for prevention of transplant rejection.