ZK824859 is An Oral Available uPA Inhibitor

Multiple sclerosis is a potentially disabling disease of the brain and spinal cord in central nervous system. Multiple sclerosis is an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body’s own tissues and organs, in this case tissues of the nervous system. Multiple sclerosis causes sensory disturbances, including a prickling or tingling sensation, numbness, pain, and itching.

Urokinase plasminogen activator system (uPAS) consists of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) and type-2 (PAI-2). uPA and PAI-1 play a key role in tumour invasion and metastasis. Moreover, The uPA system is central to a spectrum of biologic processes including fibrinoloysis, inflammation, atherosclerotic plaque formation, matrix remodeling during wound healing, tumor invasion, angiogenesis, and metastasis. And uPA is a serine protease belonging to the trypsin family that is involved in various biological processes. As a key initiator in extracellular proteolytic cascades, uPA is part of the fibrinolytic system, which includes tissue plasminogen activator (tPA), uPa receptor (uPAR), plasminogenamongst others.

ZK824859 is a selective uPA inhibitor with an IC50 of 79 nM for human uPA. Hopefully, ZK824859 especially be a effective therapeutic agents for the treatment of multiple sclerosis. In conclusion, application of uPA inhibitors may represent a new therapeutic strategy for the treatment of multiple sclerosis.