Migrastatin is a macrolide recently isolated from Streptomyces, which has been shown to inhibit human tumor cell migration. This invention provides for the total synthesis of migrastatin, as well as for novel migrastatin analogs. Several of the analogs demonstrate improved performance over migrastatin, with nanomolar IC50 values in chamber cell migration assays with tumor cells and human umbilical vein endothelial cells (HUVECs), and in wound healing assays. At least two of the analogs are potent inhibitors of metastasis in the 4T1 murine breast tumor model, reducing the number of metastasized cells in the lungs by 91 to 99 percent.
- Potential antimetastatic and antiangiogenic drug.
- The total synthesis of these compounds has been worked out.
- Migrastatin analogs with increased efficacy are also easier to synthesize than the parent compound.
Samuel J. Danishefsky, PhD
PCT applications published:
National stage applications in Canada, Europe, Japan
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