Migrastatin Analogs as Potent Tumor Cell Migration Inhibitors, with Antimetastatic Applications
SK1071
Summary of Invention
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.
Advantages
- 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.
Areas of Application
Therapeutic drugs
Stage of Development
In vivo studies in progress
Lead Inventor
Patent Information
PCT applications published:
National stage applications in Canada, Europe, Japan
References
- Oskarsson T, et al. (2010) J Am Chem Soc. 132(9):3224-8
- Perez L, Danishefsky SJ. (2007) ACS Chem Biol. Mar 20;2(3):159-62
- Krauss IJ, et al. (2007) Angew Chem Int Ed Engl. 46(29):5576-9
- Shan D, et al. (2005) Proc Natl Acad Sci U S A. Mar 8; 102(10)3772-6
- Gaul C, et al. (2004) J Am Chem Soc. Sep 15;126(36):11326-37
- Njardarson JT, et al. (2004) J Am Chem Soc. Feb 4; 126(4):1038-40
Contact Information
Peter Fong, PhD
Tel: 212-639-6181; Fax: 212-717-3439
E-mail: fongp@mskcc.org
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