GSK583

GSK583 is a highly potent, orally active and selective inhibitor of RIP2 Kinase, with IC₅₀ of 5 nM. GSK583 inhibits both TNF-α and IL-6 production with an IC₅₀ value of 200 nM. IC50 & Target: IC50: 5 nM (RIP2K)^[1] In Vitro: GSK583 (1 μM) exhibits excellent selectivity in a panel of 300 kinases, including p38α and VEGFR2. GSK583 potently and dose dependently inhibits MDP-stimulated tumor necrosis factor-alpha (TNFα) production with an IC₅₀ of 8 nM. GSK583 demonstrates only a modest reduction in potency when profiled in a similar MDP-induced TNFα production assay in human whole blood (IC₅₀ = 237 nM) and rat whole blood (IC₅₀ = 133 nM)^[1]. In Vivo: GSK583 (0.1, 1, and 10 mg/kg, p.o.) inhibits serum KC (the rodent orthologue of IL-8) levels in rats in a dose-dependent manner, with an IC₅₀ derived from rat blood concentrations of 50 nM (or 20 ng/mL). Similarly, GSK583 inhibits serum KC levels and recruitment of neutrophils into the peritoneal cavity in mice in a dose-dependent manner, with an IC₅₀ of 37 nM (15 ng/mL) derived from mouse blood concentration^[1].