Therapeutic Development of Novel HDAC2 Inhibitors

Dr. Karl Scheidt, co-director of Northwestern University’s Center for Molecular Innovation and Drug Discovery, proposes to use the Center's unique set of capabilities in drug discovery research to design, synthesize, and test new drug molecules. Recently, the enzyme histone deacetylase 2 (HDAC2) has been shown to be involved in cancer, Alzheimer ’s disease, Amyotrophic Lateral Sclerosis (ALS), and numerous other neurological disorders. We believe that drug molecules designed to selectively inhibit this enzyme may provide a new therapeutic approach to treating a variety of diseases. Using modern drug discovery techniques, we aim in this project to design and synthesize compounds that potently inhibit HDAC2. Our team will use state of the art computer-aided drug design to mimic the behavior of HDAC2 and predict novel molecular structures of compounds that potently and selectively inhibit the enzyme. We will then use sophisticated medicinal chemistry methods to synthesize new compounds. The effectiveness of the new molecules to inhibit HDAC2 will be tested using a powerful new technique that was recently pioneered by Northwestern University investigators which allows us to rapidly evaluate many such interactions simultaneously. This method will permit us to characterize how potently our new compounds inhibit this enzyme and therefore predict their usefulness as potential drug molecules. We will then conduct testing of our best compounds in cell assays that mimic various cancer and neurodegenerative diseases. We believe that this research has tremendous potential to translate the basic research being conducted at Northwestern University and turn it into potential new treatments several important diseases.