SC1: BIOCHEMISTRY AND PHARMACOLOGY OF THE UBIQUITIN-PROTEASOME SYSTEM

MONDAY, august 24 | 10:00 AM - 1:00 PM

This course is intended for the audience interested in drug discovery programs aimed to develop small molecule inhibitors targeting components of the ubiquitin-proteasome system (UPS). This course is also useful for those interested in developing proteolysis-targeting chimeric molecules (PROTACs) or molecular degraders, and should be taken concurrently with the PROTAC course, because the knowledge of the UPS system is essential to PROTAC drug discovery. The course will be well paced and cover basic mechanistic biochemistry and pharmacology of the ubiquitin-proteasome system, including E1, E2, E3, and deubiquitinating enzymes, signaling pathways they regulate, and the effect of small molecules on those pathways. We will also discuss assays and technologies currently available for the UPS system to discover enzyme inhibitors.

Topics to be Covered:

• Mechanisms of E1, E2, E3, and deubiquitinating enzymes (DUBs)
• Assays and technologies, enzyme inhibitors
• PROTACs and molecular glues

Instructor:

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.

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