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Plasminogen activator inhibitor-1 (PAI-1) is a protein involved in the fibrinolytic system and has been reported to be involved in various pathologies such as fibrosis and inflammation. We have developed small molecule inhibitors of human PAI-1 for clinical applications. A clinical candidate compound (TM5509) was finally identified among over 1400 derivatives of a hit compound (TM5275) searched by the X-ray crystal structure information of human PAI-1 and the in silico approach on a big virtual chemical library. From pre-clinical studies using our PAI-1 inhibitors, new therapeutic concepts for clinical applications, such as anti-cancer and anti-aging, have been conceived, some oh which have been tested in various investigator-initiated clinical trials.
Toshio Miyata (Tue,) studied this question.