产品描述:
Sotrastaurin is a protein kinase C (PKC) inhibitor that displays immunosuppressive activity, blocking T cell activation through the disruption of downstream NF-κB signaling.{27221,27224} In cell-free assays, sotrastaurin was reported to inhibit PKCα, βI, δ, ε, η, and θ with Ki values of 0.95, 0.64, 2.1, 3.2, 1.8, and 0.22 nM, respectively.{27221} Sotrastaurin can prevent the production of various cytokines by activated T cells, macrophages, and keratinocytes in vitro and has been shown to inhibit an acute allergic contact dermatitis response in rats when dosed orally at 30 mg.{27223} However, clinical investigation of sotrastaurin for its potential to prevent renal transplant rejection was halted during phase II testing due to high incidence of rejection.{27222} Sotrastaurin is also reported to activate Wnt/β-catenin signaling via the inhibition of glycogen synthase kinase 3 (IC50s = 229 and 172 nM for α and β isoforms, respectively), which is essential for embryogenesis and adult stem cell maintenance.{27225,27226}