Cancer
The goal of the Cancer group is to generate improved methods for: 1) treatment of cancer, and 2) detection/diagnosis. Our interdisciplinary team is actively pursuing novel structure-based strategies to define therapeutic agents to treat a diverse set of cancer cell types including breast, pancreas, liver, colorectal, lung, multiple myeloma, lung and prostate. This strategy is based on the atomic structures of proteins involved in specific mechanisms that promote uncontrolled cell growth and division. We utilize x-ray crystallography and a combination of cellular, molecular, biochemical/biophysical techniques to establish structure-function relationships between candidate drug molecules and targeted proteins in transformed cells. An outstanding feature of this method is a unique high-throughput virtual screening method in which large chemical libraries are screened for their abilities to interact with proteins involved in cancer.
We routinely screen two compound collections: the repository at the National Cancer Institute Developmental Therapeutics Program (approximately 140,000 compounds), and all non-proprietary drug-like molecules in the public domain (approximately 6 million compounds). This rapid and economical method utilizes one of the most powerful supercomputers, located at the University of Florida at the High-Performance Computing facility (ranked in the Top 500 supercomputers worldwide, hpc.ufl.edu).
The Cancer division of EP faculty is capable of defining and screening drug candidates for their abilities to interact with target proteins in addition to conducting preclinical testing using biochemical, biophysical, cellular and whole animal methods.
For example, we recently identified a drug capable of interacting with a protein that plays important roles in a diverse set of cancer cell types, the Focal Adhesion Kinase. We demonstrated that this drug inhibits the activity of Focal Adhesion Kinase at the biochemical and cellular levels. We also co-crystallized the drug bound to Focal Adhesion Kinase and solved its structure by x-ray crystallography. Next, we demonstrated that this drug can be used to inhibit the growth of human tumors in mice. We demonstrated that drug is potent in inhibiting the growth of breast and pancreatic cancer in vivo.
Visit my.ufscc.ufl.edu/memarea/sbdd/index.htm for more information and to initiate new projects aimed at early detection and novel treatments for cancer.
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