SC3: Targeted Protein Degradation as a New Therapeutic Approach

SUNDAY, MARCH 1 | 2:00 - 5:00 PM

ABOUT THIS COURSE:

Targeted protein degradation using molecular glues and bifunctional small molecules known as proteolysis-targeting chimeric molecules (PROTACs) are emerging as a useful tool for drug discovery, and as a new therapeutic modality for chasing previously “undruggable” targets. This course will cover the basic understanding of what these entities are, how they work and how they can be applied to target and degrade specific proteins of interest. Case studies drawn from the work that the instructors have done in their labs will also be presented.

COURSE AGENDA:

2:00 pm Course Introduction

2:10 Introduction to Protein Degradation

Alexander Statsyuk, PhD, Assistant Professor, Department of Pharmacological and Pharmaceutical Sciences, University of Houston

• Basic mechanistic biochemistry and pharmacology of the ubiquitin proteasome system
• Overview of E1, E2, E3, and deubiquitinating enzymes (DUBs)
• Introduction to PROTACs and molecular glues

2:45 Targeting Undruggable Targets

Shaomeng Wang, PhD, Warner-Lambert/Parke-Davis Professor of Medicine, Pharmacology and Medicinal Chemistry; Co-Director, Molecular Therapeutics Program and Director, Cancer Drug Discovery Program, University of Michigan

• Designing potent, selective, and highly efficacious degraders

3:20 Refreshment Break

4:10 Optimizing for Selectivity and Delivery

Ingrid Wertz, MD, PhD, Senior Scientist, Departments of Molecular Oncology and Early Discovery Biochemistry, Genentech, Inc.

• Modalities for achieving selective protein degradation
• Case studies evaluating deubiquitinase inhibitors and antibody-mediated delivery of degradation-inducing compounds

4:45 Q&A with Attendees/Speakers

5:00 Course Ends

INSTRUCTORS:

Alexander Statsyuk, PhD, Assistant Professor, Department of Pharmacological and Pharmaceutical Sciences, University of Houston

Alexander Statsyuk is an assistant professor at the University of Houston College of Pharmacy. He obtained his PhD degree at the University of Chicago in 2006, where he synthesized natural product Bistramide A and established its mode of action in cells. He then completed his postdoctoral work at UCSF, where he was working on the development of chemical cross-linkers to identify upstream kinases of protein phosphorylation sites. Since 2010 he has been running his independent research program aimed at discovering drug leads targeting degradation pathways such as ubiquitin proteasome system and autophagy. He is an author of 32 manuscripts, he filed 10 patent applications, and he is a recipient of Pew Scholar Award. Some of the technologies that he and his group have developed and patented include covalent fragments, novel probes UbFluor to conduct HTS screens to discover E3 ligase inhibitors, activators, and hijackers, and E3-Substrate cross-linkers useful to study E3-Substrate interactions in vitro and to validate E3-Substrate hijackers in vitro.

Shaomeng Wang, PhD, Warner-Lambert/Parke-Davis Professor of Medicine, Pharmacology and Medicinal Chemistry; Co-Director, Molecular Therapeutics Program and Director, Cancer Drug Discovery Program, University of Michigan

Dr. Shaomeng Wang obtained his chemistry BS degree from Peking University in 1986 and his PhD in Chemistry from Case Western Reserve University in 1992. Dr. Wang did his postdoctoral training at NIH before becoming an assistant professor in Georgetown University in 1996. Dr. Wang is currently the Warner-Lambert/Parke Davis Professor in Medicine in the University of Michigan Medical School and professor of medicine, pharmacology and medicinal chemistry. Dr. Wang is the Director of University of Michigan Center for Therapeutic Innovation and Cancer Drug Discovery Program at the University of Michigan. Dr. Wang has served as the Editor-in-Chief of the Journal of Medicinal Chemistry, American Chemical Society since 2012. Dr. Wang has co-founded 5 biotech companies to develop novel small-molecule drugs invented from his laboratory and has advanced 7 compounds into clinical development. Dr. Wang has published >300 peer-reviewed papers and is an inventor of 54 issued US patents and hundreds of international patents. Dr. Wang was elected as Fellow of the National Academy of Inventors in 2014 and was the 2014 University of Michigan Distinguished Innovator.

Ingrid Wertz, MD, PhD, Senior Scientist, Departments of Molecular Oncology and Early Discovery Biochemistry, Genentech, Inc.

Dr. Wertz performed her graduate studies at Genentech via an NIH Biotechnology Training Grant. Here she learned that rigorous scientific experimentation is the foundation for rational drug design. Dr. Wertz continued her training in the Medical Scientist Training Program at Washington University in St. Louis, where she witnessed the positive impact that effective medicines can have on patients. She chose to return to Genentech as a scientist in order to help patients through scientific discoveries. Her aims are to understand the molecular basis of disease and to translate those findings into novel therapeutics. Dr. Wertz is currently a Senior Scientist in the departments of Discovery Oncology and Early Discovery Biochemistry at Genentech, where she leads a research lab and directs drug discovery efforts focused on co-opting the ubiquitin/proteasome system.

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