Biochemical mechanism of action of a diketopiperazine inactivator of plasminogen activator inhibitor-1
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چکیده
منابع مشابه
Biochemical mechanism of action of a diketopiperazine inactivator of plasminogen activator inhibitor-1.
XR5118 [(3 Z,6 Z )-6-benzylidine-3-(5-(2-dimethylaminoethyl-thio-))-2-(thienyl)methylene-2,5-dipiperazinedione hydrochloride] can inactivate the anti-proteolytic activity of the serpin plasminogen activator inhibitor-1 (PAI-1), a potential therapeutic target in cancer and cardiovascular diseases. Serpins inhibit their target proteases by the P(1) residue of their reactive centre loop (RCL) form...
متن کاملBiochemical properties of plasminogen activator inhibitor-1.
PAI-1 is a Mr ~50,000 glycoprotein, which is the primary physiological inhibitor of the two plasminogen activators uPA and tPA. PAI-1 belongs to the serpin protein family. Studies of PAI-1 have contributed significantly to the elucidation of the protease inhibitory mechanism of serpins, which is based on a metastable native state becoming stabilised by insertion of the RCL into the central beta...
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Background: Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein with inhibitory effects on the formation of plasmin from plasminogen by plasminogen activator. Thus, it prevents clot lysis in vessel walls. Several evidences prove the relationship between coronary artery disease and response to fibrinolytic therapy in patients with myocardial infarction with PAI-1 level. Opium addiction i...
متن کاملMechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1.
Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) family. Excessive PAI-1 activity is associated with human disease, making it an attractive pharmaceutical target. However, like other serpins, PAI-1 has a labile structure, making it a difficult target for the development of small molecule inhibitors, and to date, there are no US Food and Drug A...
متن کاملThe mechanism of the reaction between human plasminogen-activator inhibitor 1 and tissue plasminogen activator.
The structural events taking place during the reaction between PAI-1 (plasminogen-activator inhibitor 1) and the plasminogen activators sc-tPA (single-chain tissue plasminogen activator) and tc-tPA (two-chain tissue plasminogen activator) were studied. Complexes were formed by mixing sc-tPA or tc-tPA with PAI-1 in slight excess (on an activity basis). The complexes were purified from excess PAI...
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ژورنال
عنوان ژورنال: Biochemical Journal
سال: 2003
ISSN: 0264-6021,1470-8728
DOI: 10.1042/bj20021880