Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease found in humans and other animals. Specifically, UPA is relevant to tissue remodeling and cell migration. The active form of uPA binds to its high-affinity receptor on the cell surface, and specific inhibitors can regulate its enzyme activity. Besides, the combination of uPA and uPAR contributes to the activation of plasminogen into plasmin. Moreover, it then initiates a series of proteolytic cascade reactions to degrade the components of the extracellular matrix. This results in the migration of tumor cells from the primary site to the distance. The increased expression levels of urokinase and other components of the plasminogen activation system are relevant to tumor malignancy.

Furthermore, UPA is more often associated with cancer progression than tissue plasminogen activator (TPA). UPA antigen is more in breast cancer tissue, which is relevant to the poor prognosis of breast cancer patients. Therefore, uPA is a biomarker for the diagnosis of breast cancer. The components of the uPA-uPAR system acts as excellent candidates for anticancer therapy. Meanwhile, inhibitors are anticancer agents. Here, we will introduce a selective urokinase-type plasminogen activator (uPA) inhibitor, UK122.

UK122 is a Selective Urokinase-Type Plasminogen Activator (uPA) Inhibitor.

Firstly, UK122 is a potent and selective uPA inhibitor with an IC50 of 0.2 μM. UK122 shows no or little inhibition of tissue-type PA (tPA), plasmin, thrombin, and trypsin (all IC50>100 μM). Nonetheless, UK122, 4-oxazolidinone analog, is an anticancer agent and inhibits cancer cell migration and invasion.

Secondly, UK122 with 11.1-100 μM for 24 h dose-dependently inhibits cell migration and significantly reduces the invasiveness of CFPAC-1 cells. Interestingly, UK122 has no effect of any cell growth or cell morphology change in CFPAC-1 cells.

Once again, UK122 inhibited trypsin activity by 38%, thrombin by 8%, and tPA by 5% at 100 μM. Particularly, UK122 showed no inhibitory activity against plasmin at 100 μM.

All in all, UK122 is a potent and selective urokinase-type plasminogen activator (uPA) inhibitor.


Ming Zhu, et al. Mol Cancer Ther. 2007 Apr;6(4):1348-56.