Seminar with Dr. Eli Chapman from University of Arizona

The University of Central Florida, Department of Chemistry, presents Dr. Eli Chapman, Department of Pharmacology & Toxicology, College of Pharmacy, University of Arizona.  He will give a seminar entitled, “Withanolides that target the AAA+ chaperone p97”

Thursday, April 9, 2015
3:00-4:00 p.m.
Health & Public Affairs I
Room 126

His presentation will cover the following:
Understanding the mode of action of natural products can be puzzling, particularly for compounds whose mechanistic clues seem to lack a common thread. One such puzzle lies in the evaluation of the antitumor properties of the natural product withaferin A. A variety of seemingly unrelated pathways have been identified to explain its activity, suggesting a lack of selectivity. We now show that withaferin A acts as an inhibitor of the chaperone, p97. Then through medicinal chemistry, we have increased potency.  Subsequent studies indicated that these analogs retained p97 activity and cytotoxic activity in cell models, suggesting that the modes of action (MOAs) reported for the withanolides are connected by proteostasis modulation. Through this endeavor, we highlight how the parallel integration of medicinal chemistry with chemical biology offers a potent solution to some of natures’ more intriguing molecular puzzles.