For research use only. Not Intended for Therapeutic Use!
|IC50:||1 nM |
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Tofacitinib(CP-690550 citrate) is a novel inhibitor of JAK3 with IC50 of 1 nM, 20- to 100-fold less potent against JAK2 and JAK1.
IC50 value: 1 nM 
in vitro: CP-690550 is a specific, orally inhibitor of JAK3, it is 20- to 100-fold less potent for JAK2 and JAK1 with IC50 of 20 nM and 112 nM, respectively. CP-690550 doesn/'t have potent activity against 30 other kinases (all median IC50 > 3000 nM). CP-690,550 inhibits IL-2–induced proliferation with 30-fold greater potency than its effects on GM-CSF–induced proliferation . CP-690550 effectively inhibits a murine mixed lymphocyte reaction (MLR) (IC50 = 91 nM) . CP-690550 potently inhibits IL-4 induced upregulation of CD23 (IC50=57 nM) and class II major histocompatibility complex (MHCII) expression (IC50=71 nM) on murine B cells .
in vivo: In a murine model of heterotopic heart transplantation (DBA2 donor heart into C57/BL6 host), CP-690550 results in a dose-dependent increase in survival of transplanted hearts.The EC50 (drug concentration in blood at which 50% of mice will maintain their graft for >28 days) to be ~60 ng/mL.CP-690550 prevents rejection of allogeneic kidneys in nonhuman primate (NHPs, macaca fascicularis) (MST of 62 and 83 days for the 50 to 100 ng/ml groups and 200 to 400 ng/ml groups, respectively) . Mice chronically dosed with CP-690550 (1.5-15 mg/kg/day) demonstrates dose and time-dependent alterations in lymphocyte subsets when examined by flow cytometry. The most dramatic change observed is a 96% reduction in splenic NK1.1+TCRb-cell numbers following 21 days of treatment. Delayed-type hypersensitivity (DTH) responses in sensitized mice are reduced in a dose-dependent manner following treatment with CP-690550 (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 is observed with CP-690550 monotherapy (10–30 mg/kg/day), but improved upon combination with cyclosporin (10 mg/kg/day) .
. Changelian PS, et al, Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science, 2003, 302(5646), 875-878.
. Kdlacz E, et al, The novel JAK-3 inhibitor CP-690550 is a potent immunosuppressive agent in various murine models. Am J Transplant, 2004, 4(1), 51-57.
. Kudlacz E, et al, The JAK-3 inhibitor CP-690550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia.Eur J harmacol, 2008, 582(1-2), 154-161.