Synthesis and evaluation of novel kinase inhibitors as anti-metastasis agents for

PROJECT SUMMARY Metastasis is a key factor for poor prognosis in cancer patients. Ovarian cancer is the fifth most common gynecological cancer causing significant mortality among women. Breast cancer is the most common invasive cancer in women and the second-most common cause of death in American women. Triple negative breast cancer tends to be both unresponsive to chemotherapy and more aggressive than other types of breast cancer. New therapies to prevent spread of these cancer types are urgently needed. There is recent scientific evidence that both migration and cytoskeleton rearrangement associated with metastases of these cancer types is controlled by a specific protein kinase. By using a rational design approach that combines structural protein kinase information and optimal ADME properties, we have discovered a novel series of potent kinase inhibitors. The goal of this work is to optimize our newly discovered series of inhibitors as agents to prevent metastasis in triple negative breast cancer and ovar