Discovery of FAK Inhibitors Using Structure Based Drug Design

摘要

Focal adhesion kinase (FAK) is a 125-kDa non-receptor protein tyrosine kinase that associates with both integrin receptors and some growth factor receptor tyrosine kinases to control cell motility, invasion and survival. FAK1 has been demonstrated to modulate cancer cell proliferation, survival, migration and angiogenesis. FAK1 is overexpress-ed in invasive or metastatic breast and colon cancer4 whereas knocking down FAK1 elevated p53 and p21 levels and reduced cell proliferation. In addition, translocation of nuclear FAK1 facilitates cell survival through enhancing p53 degradation under conditions of cellular stress.