| References: |
KBU2046 represents a new and chemically distinct class of bioactive compounds. It has greater anti-invasion efficacy than genistein, and more importantly, no cell toxicity or estrogenic activity. Extensive toxicity studies in mice were negative. At low nanomolar blood concentrations, KBU2046 will prevent orthotopically implanted human prostate cancer cells from forming metastasis in a dose-responsive fashion. In summary, we have successfully discovered and developed a compound that prevents progression to a metastatic phenotype for human prostate cancer.KBU2046 inhibits cell motility and cell invasion in vitro. Across three different murine models of human prostate and breast cancer, KBU2046 inhibits metastasis, decreases bone destruction, and prolongs survival at nanomolar blood concentrations after oral administration. Comprehensive molecular, cellular and systemic-level assays all support a high level of selectivity. KBU2046 binds chaperone heterocomplexes, selectively alters binding of client proteins that regulate motility, and lacks all the hallmarks of classical chaperone inhibitors, including toxicity. |
