DETROIT- Suppressing an enzyme that promotes tumor growth is the goal of a $1.3 million study led by Wayne State researcher Patrick M. Woster, Ph.D., professor of pharmaceutical sciences in the Eugene Applebaum College of Pharmacy and Health Sciences and resident of Canton, Mich.

Woster received $1,311,950 from the National Cancer Institute of the National Institutes of Health (NIH) to identify and develop compounds that inhibit lysine-specific demethylase 1 (LSD1), an enzyme that has been shown to prevent the production of proteins that are important to tumor suppression. Woster and co-principal investigator Robert A. Casero Jr., Ph.D., from John Hopkins University, have discovered novel molecules that inhibit LSD1, enabling the tumor-suppressor proteins to be re-expressed. Preliminary research has shown that when used in animals in combination with traditional antitumor agents, these molecules can prevent tumor growth.

The current study will further test the compounds' ability to inhibit LSD1, to re-express tumor suppressor proteins and limit tumor growth in an animal model.

"Previous studies have identified the enzyme LSD1 as an exciting new target for inhibiting tumor growth," Woster said. "Recently, we've reported a series of molecules - guanidines and biguanidines - that are potent inhibitors of this enzyme. The goal of our current study is to synthesize additional molecules and develop these compounds further, so that they may be used for the treatment of human cancer."
Woster and Casero Jr. were the first to demonstrate the antitumor effects of LSD1 inhibitors in vitro and recently demonstrated the antitumor effects in vivo.

For the study, Woster will design and synthesize multiple series of analogues, generating compound libraries of potential small-molecule LSD1 inhibitors. They will also use virtual screening to identify leads from commercial databases and to suggest more potent analogues for synthesis and screening. They will then evaluate the newly synthesized analogues effectiveness as inhibitors in cultured tumor cells and finally, in combination treatments in animal models.

"By evaluating a variety of analogues using several different methods, our study aims to find the most potent inhibitor of LSD1 possible," Woster said. "Using this approach, there is a high probability that a potent LSD1 inhibitor could become an important new class of antitumor agents."
 

                                                                                                             # # #

Wayne State University is one of the nation's pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information on research at Wayne State University, visit http://www.research.wayne.edu.