UCN-01 AND UCN-02, NEW SELECTIVE INHIBITORS OF PROTEIN KINASE C

I. SCREENING, PRODUCING ORGANISM AND FERMENTATION

Abstract

In the course of continued screening program for new selective inhibitors of protein kinase C (PKC), fermentation broths from over 5, 000 soil isolates were screened for their inhibitory activity of PKC. HPLC analysis of active cultures revealed that five different strains (N-71, N-115, N-126, N-128 and N-139) of Streptomyces isolated from various local soil samples were found to produce staurosporine and related compounds. Of these strains, N-126, a high producing strain, was found to produce new selective inhibitors of PKC, UCN01 and its stereoisomer, UCN-02. The pH control of fermentation resulted in an increase of the production of UCN-01 and UCN-02.