NF-kB regulates the expression of over 200 genes that are involved in a variety of functions such as immune regulation, cell growth, and inflammation. Aberrant NF-kB activity is associated with a number of disease states such as cancer, diabetes, inflammatory disorders, and autoimmune diseases. Since the NF-kB pathway plays an important role in the development and progression of numerous diseases it is an ideal candidate for the development of therapeutic compounds. Researchers at the University of Nebraska Medical Center have identified a set of compounds that act as inhibitors of the NF-kB pathway. From this set of compounds a lead compound, 13-197, was identified and characterized. 13-197 was tested in a panel of cancer cell lines and demonstrated potent antiproliferative activity. Further tests demonstrate that 13-197 inhibits NF-kB mediated gene transcription, enhances caspase 3/7 activity, induces apoptosis, and sensitizes pancreatic cancer cells to chemotherapeutic agents such as gemcitabine. Mechanistic studies suggests that 13-197 inhibits a previously unexplored target in the NF-kB pathway. Initial PK studies have been conducted on 13-197 and show that 13-197 is orally available and cleared mainly through the liver and the kidney. In vivo efficacy studies using a pancreatic cancer model are currently underway.

File Number: 234 

Web site: http://www.unemed.com

Disease: Cancer