An α2-Macroglobulin Inhibitor, API-13782, Produced by Streptomyces canus OFR-1267

About 7000 microbial culture filtrates have been screened for inhibition of α2-macroglobulin, one of the plasma protease inhibitors. One strain, identified as Streptomyces canus, was found to produce a potent inhibitor named API-13782. The inhibitor was purified from the culture filtrate by column chromatographies on Daiaion HP-20 and Dowex 1 × 2, and then by high performance liquid chromatography. API-13782 was an acidic compound of low molecular weight of, 441. It showed time-independent, fairly specific inhibition against α2-macroglobulin, and required some kinds of divalent metal ions such as Ca++, Mn++, or Co++ for development of its inhibitory action. In serum the activity of plasmin formed by urokinase, a plasminogen activator, was increased by preteatment with API-13782. This suggests that API-13782 is clinically useful as a potentiator of urokinase.