July 26, 2016
CHARLESTON, SC – Patrick M. Woster, Ph.D., SmartState endowed chair in drug discovery and professor and chair of the Department of Drug Discovery & Biomedical Sciences, received a $1.35 million National Institutes of Health (NIH) award to develop novel inhibitors of the SMOX enzyme.
Chronic inflammation is known to play a role in the development of various forms of cancer. It was recently discovered that the polyamine catabolic enzyme spermine oxidase (SMOX) is abnormally induced in chronic inflammatory conditions, including Helicobacter pylori (H. pylori) associated gastritis, where production of hydrogen peroxide by excess SMOX contributes to DNA damage and the production of gastrointestinal tumors (esophagusgus, stomach, pancreas, small intestine, large intestine and rectum).
Recent studies have reported that chronic infection with H. pylori may increase the risk of stomach cancer. These data have come from large population studies comparing the rates of H. pylori infection in patients with stomach cancer to those without stomach cancer. Roughly two-thirds of the world’s population carries the bacteria H. pylori. This spiral-shaped bacterium grows in the mucus layer that coats the inside of the stomach.
In collaboration with Robert A. Casero, Jr., M.D., professor of oncology at the Johns Hopkins University School of Medicine and associate director for shared resources at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Woster plans to synthesize and test selective inhibitors of enzyme SMOX that can serve as a type of chemical probe for the identification of chemopreventive agents. Casero and Woster identified their lead compounds by chance, while conducting unrelated experiments. The term "chemopreventive agent" refers to a type of drug or vitamin that helps protect healthy tissue from turning into cancer.
“When you undertake a drug discovery program, it is important to ensure that potential drugs are specific for the target,” Woster said. He will use multiple medicinal chemistry approaches to identify and synthesize potential inhibitors of SMOX, followed by hit-to-lead optimization of selected compounds with therapeutic potential. He plans to conduct physical screening of compound libraries, as well as chemical synthesis of analogues based on new and existing scaffolds. In conjunction with these studies, he will conduct preliminary evaluation of compounds against SMOX.
The collaboration between Casero and Woster began in 1993, and has resulted in more than 50 publications in peer-reviewed scientific journals, and in five jointly held patents. They have recently formed a new company, Inquisatex Epitherapeutics, LLC, that will be used to develop compounds synthesized and developed through their collaborative efforts.
Woster joined MUSC in 2011 to develop drugs that control the expression of genes in tumor cells, a process known as epigenetic modulation, which can be used to make traditional antitumor medications more effective. In addition to his work in the cancer field, he and his team are working to discover new treatments for infectious diseases such as malaria and other parasitic illnesses.
"Our goal is to develop a world-class drug discovery program at MUSC by providing a core facility for drug synthesis and compound development, and by teaming up with existing centers within the university, such as Hollings Cancer Center," Woster said. "The discovery of successful, improved agents for the treatment of cancer would have a significant impact on the lives of patients in South Carolina and beyond. We hope to increase the scope of our research efforts to include many aspects of the drug development process that will ultimately lead to early and late stage human clinical trials."
MUSC Hollings Cancer Center is a national leader in the diagnosis and treatment of gastrointestinal malignancies, which include cancers of the esophagus, stomach, pancreas, liver, biliary tree, colon, and rectum. The cancer center works in close collaboration with the MUSC Digestive Disease Center, rated highly for many years by U.S. News & World Report for the treatment of gastrointestinal disorders.
Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and 700 residents in six colleges (Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing, and Pharmacy), and has nearly 14,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.4 billion, with an annual economic impact of more than $3.8 billion and annual research funding in excess of $250 million. MUSC operates a 700-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute-designated center), Level I Trauma Center, Institute of Psychiatry, and the state’s only transplant center. In 2017, for the third consecutive year, U.S. News & World Report named MUSC Health the number one hospital in South Carolina. For more information on academic programs or clinical services, visit musc.edu. For more information on hospital patient services, visit MUSChealth.org.