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Urokinase inhibitors target urokinase-type plasminogen activator (uPA), a serine protease that generates plasmin. uPA is secreted as a single-chain proenzyme and binds a glycolipid-anchored receptor, the uPA receptor (uPAR). The receptor was cloned in 1990 and concentrates plasminogen activation at the cell surface. Plasmin degrades extracellular matrix proteins and activates latent growth factors, linking the system to cell migration and tumor invasion. uPAR also signals through integrins and other membrane partners, independent of proteolysis. Small-molecule uPA inhibitors include 4-Chlorophenylguanidine hydrochloride, BC 11 hydrobromide and ZK824190. GGACK Dihydrochloride is a peptide chloromethyl ketone that inactivates the protease irreversibly. Cenupatide differs from the others because it acts on uPAR rather than the enzyme.
