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PAI-1 inhibitors act on plasminogen activator inhibitor 1, the main brake on fibrinolysis. PAI-1, encoded by serpin family E member 1 (SERPINE1), is a serine protease inhibitor (serpin). It inactivates tissue-type and urokinase-type plasminogen activators (tPA, uPA), which convert plasminogen into the fibrin-degrading protease plasmin. Active PAI-1 converts spontaneously into an inactive latent form, so its activity in samples changes over time. Raised PAI-1 has been linked to thrombosis, obesity and tissue fibrosis, which are studied in animal models. Tiplaxtinin (PAI-039), TM5275 sodium and TM5441 are small-molecule PAI-1 inhibitors that restore plasminogen activator activity. UK-371804 and ZK824859 instead inhibit uPA, acting on the protease rather than its inhibitor.
