ZK824859

ZK824859 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].

Signaling Pathways >> Metabolic Enzyme/Protease >> PAI-1

Research Areas >> Inflammation/Immunology

IC50: 79 nM (human uPA), 1580 nM (human tPA), 1330 nM (human plasmin)[1].

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].

ZK824859 shows efficacy in acute and chronic EAE model for multiple sclerosis. In a chronic mouse EAE model at a dose of 50 mg/kg b.i.d. ZK824859 completely prevents the development of disease. However, two lower doses (25 and 10 mg/kg) have no effect on clinical scores. In an acute mouse EAE model, ZK824859 is also efficacious. In this study the 50 and 25 mg/kg b.i.d. doses show a reduction in clinical scores compared to the control group, although only the 25 mg/kg treatment regime is statistically significant compared to the control group[1].

[1]. Islam I, et al. Discovery of selective urokinase plasminogen activator (uPA) inhibitors as a potential treatment for multiple sclerosis. Bioorg Med Chem Lett. 2018 Nov 1;28(20):3372-3375.