Adventures in Academic Cancer Drug Discovery: Novel Inhibitors of the AAA ATPase p97
Dr. Donna Huryn
October 19 at 12:20pm in the Fralin Auditorium, Fralin Hall room 102
Hosted by Webster Santos
Donna M. Huryn received her B.A. (Chemistry) from Cornell University, and Ph.D. in Organic Chemistry from the University of Pennsylvania. After graduate school, she joined the Chemistry Research Department at Hoffmann-La Roche, Inc, and contributed to drug discovery efforts in inflammation, HIV and cancer with increasing levels of responsibility. In 1997 she moved to Wyeth Research’s Chemical Sciences department. She held a number of positions there, including Director of CNS Medicinal Chemistry and Director of the Chemical Sciences Interface Department. Under her leadership, compounds entered clinical trials for asthma, Alzheimer’s disease, schizophrenia and depression. In 2004, she left the pharmaceutical industry to join academia. She is on the faculty at the University of Pittsburgh’s School of Pharmacy, and holds an adjunct appointment in the Department of Chemistry at the University of Pennsylvania. She is a Fellow of the American Chemical Society, recipient of the ACS Philadelphia Local Section Award, has held a number of elected positions within the American Chemical Society at both the local and national levels, and is 2015 Chair of the Division of Organic Chemistry. She is Associate Editor of ACS Medicinal Chemistry Letters. Professor Huryn’s research focuses on the design and synthesis of small molecules probes and drugs to treat cancer, neurodegenerative and infectious diseases.
Through the National Cancer Institute’s (NCI’s) Chemical Biology Consortium, a team of scientists representing multiple institutions have discovered and developed novel allosteric inhibitors of the AAA ATPase p97 (VCP), an exciting, emerging target in cancer. p97 is a master regulator of protein homeostasis and modulates ubiquitin-dependent degradation as well as membrane fusion activities throughout the cell. These events are directed by a network of protein-protein interactions and ATPase-dependent changes in p97 conformation. The team has designed and optimized allosteric inhibitors that inhibit p97 with biochemical IC50s in the range of 10-200nM and sub-micromolar cell based activity. We solved the first high-resolution structures of p97 bound to an inhibitor using cryo-electron microscopy, and have developed a binding model of these allosteric inhibitors. We aim to develop new experimental therapeutics and can also use these molecules to decipher the complex biological pathways regulated by p97 activity.
This seminar has no suggested readings.