Colloquium Talk
Prof. Brian S. J. Blagg
Notre Dame
Chemistry and Biochemistry
Thursday, November 20, 2025
MoSe G011
3:30pm - 4:30pm
Title: The Design and Synthesis of Modern Hsp90 Inhibitors and their Biological Opportunities
Abstract:
The Hsp90 molecular chaperone is composed of four family members that play key roles in the folding of nascent polypeptides as well as the rematuration of misfolded proteins. The cytosolic chaperones, Hsp90a and Hsp90b, contribute to tumorigenesis and represent attractive targets for the treatment of cancer. Grp94 is the ER-localized paralog that is responsible for the trafficking of proteins, such as myocilin, and consequently represents an ideal target for the treatment of primary open-angle glaucoma. In contrast to the inhibition of Hsp90, molecular chaperones can be overexpressed to exhibit neuroprotective activity, which is currently undergoing Phase II clinical evaluation. While the Hsp90 isoforms play key roles in various diseases, the N-terminal ATP-binding site is >85% identical, making the development of selective inhibitors challenging. In this presentation, the methods used to develop isoform-selective inhibitors will be disclosed, along with some of the preclinical studies that are currently underway.
Bio:
Dr. Blagg is currently the director of the Warren Family Research Center for Drug Discovery and Development and the Charles Huisking Professor of Chemistry and Biochemistry at the University of Notre Dame. He initially received a B.A. in Chemistry and Environmental Studies from Sonoma State University in 1994 and then earned his Ph.D. in organic chemistry from the University of Utah, working in Dale Poulter’s laboratory. Following his Ph.D., he was a NIH postdoctoral fellow at the Scripps Research Institute, where he studied in Dale Boger’s laboratory until 2002. He worked to become a Professor and served as a Professor of Medicinal Chemistry at the University of Kansas from 2002 to 2017, before joining the faculty at the University of Notre Dame. His research focuses on the design, Synthesis, and evaluation of HSP90 inhibitors.