ZK824859 (hydrochloride)

ZK824859 hydrochloride is an oral available and selective urokinase plasminogen activator (uPA) inhibitor with IC₅₀s of 79 nM, 1580 nM and 1330 nM for human uPA, tPA, and plasmin, respectively^[1]. IC50 & Target:IC50: 79 nM (human uPA), 1580 nM (human tPA), 1330 nM (human plasmin)^[1]. In Vitro: ZK824859 is 5 fold less potent and has lost selectivity in mouse: uPA IC₅₀=410 nM; tPA IC₅₀=910 nM; plasmin IC₅₀=1600 nM compared to human IC₅₀ values of 79 nM, 1580 nM and 1330 nM respectively^[1]. In Vivo: ZK824859 (50, 25 and 10 mg/kg; b.i.d.; 25 days) is used in a chronic mouse EAE model. ZK 824859 completely prevents the development of disease. However, two lower doses (25 and 10 mg/kg) have no effect on clinical scores^[1].