Information
Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor ofJAK3withIC50of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1. Tofacitinib inhibits the expression of antiapoptoticBCL-A1andBCL-XLin human plasmacytoid dendritic cells
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. A recent research indicates low dose of CP-690550 accelerates the onset of experimental autoimmune encephalomyelitis by potentiating Th17 differentiation.
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).
Cell Data
cell lines：ZR-75-30, HCC-1419, MDA-MB-175, BT-474, SKBR3, MDA-MB-361, UACC-812, T-47D, MDA-MB-453, MDA-MB-468, CAMA-1, MDA-MB-157, MCF-7, MDA-MB-435, ZR-75-1, BT-20, and MDA-MB-231.
Concentrations：0-4000 nM
Incubation Time：4 days
Powder Purity:≥99%
