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placenta, platelet and hepatoma cells9~n). Heparinase I, II and III cloned from Flavobacterium heparinumn\ are the other enzymes that degrade such HLG molecules that have been actively studied. These three enzymes are unique in their action since they cleave along the HLGs backbone with high degree of specificity13). In addition, heparinases were implicated in many growth factor-mediated cellular signaling14). There also were reports about the inhibition of the metastatic melanoma cells and other tumor cells by heparin and its derivatives15'16). Hence, heparinase inhibitors might provide useful tools for the elucidation of biological functions of heparin and HS and can be used as antimetastatic agents. In the course of screening for heparinase inhibitors from microbial metabolite through a modified assay system for heparinase, we isolated novel inhibitors, CRM646-A (1)

CRM646-A and -B, Novel Fungal Metabolites that Inhibit Heparinase.