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Also on the trail of iminosugar-based drugs are Yoshio Nishimura, associate director of the Microbial Chemistry Research Center, Tokyo, and coworkers. They are pursuing iminosugar inhibitors of enzymes involved in tumor metastasis as potential cancer therapeutics.
According to Nishimura, tumor metastasis occurs by a complex multistage process that includes tumor invasion through blood vessel membranes. To enter and exit blood vessels, many kinds of tumor cells secrete heparanase to break down vascular membranes. Nishimura and coworkers have synthesized geminal-diamine 1-N-iminosugars that block the activity of heparanase and thereby inhibit tumor metastasis efficiently in animal models.
Among these are SF-4 and SDD-8, potent inhibitors of heparanases associated with melanoma. Both have been shown to prevent cancer cell invasion in membrane assays and to potently suppress pulmonary metastasis of tumors in mice, and neither has shown toxicity in the mouse studies. In addition, "we have developed a better candidate and are now evaluating its activity in vivo," Nishimura said.
The agents are candidates for chemotherapeutics to prevent cancer spread. The researchers are still trying to optimize them, and "a company is interested in them for preclinical trials," Nishimura said
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