The ubiquitin-proteasome system (UPS) is a well-controlled, selective mechanism for intracellular protein degradation and turnover, and it acts as a key regulator in cancer, CNS and other diseases. However, the multi-step processes involved, and the diversity of substrates makes it difficult to target the UPS. Proteolysis-targeting chimeric molecules (PROTACs) are a group of engineered hetero-bifunctional chemical entities that bind to the target and ligase to mediate ubiquitination and subsequent protein degradation. Like PROTACs, other chemical entities and molecular glues, using varied mechanisms-of-action, are being developed to trigger targeted protein degradation. These approaches have a lot of potential in seeking out previously “undruggable” protein targets for applications in drug discovery and for developing new therapeutic modalities. However, some challenges do exist in terms of stability, biodistribution and penetration of these molecules in vivo. Cambridge Healthtech Institute’s conference on PROTACs and Targeted Protein Degradation will bring together a diverse group of chemists and biologists to discuss the prospects, as well as, the challenges underlying strategies for targeted protein degradation. This will be preceded by a conference that discusses emerging ubiquitin and autophagy targets for therapeutic intervention.
IMPROVING SPECIFICITY & SELECTIVITY OF DEGRADATION
FEATURED PRESENTATION: Targeting the Undruggables Using PROTACs
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
Computational Design of PROTACs
Ye Che, PhD, Head of Computational Design, Discovery Sciences, Pfizer, Inc.
Structure-Based Design of Degraders
Radoslaw Novak, PhD, Scientist, Laboratory of Dr. Eric Fischer, Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School
IDENTIFYING NEW LIGANDS & TARGETS FOR DEGRADATION
Screening and Identification of Novel PROTAC Ligase Ligands
Markus Queisser, PhD, Scientific Leader, Protein Degradation DPU, R&D Future Pipelines Discovery, GlaxoSmithKline
Establishing a Platform for High-Throughput Identification and Profiling of Target Degraders
James Robinson, PhD, Associate Principal Scientist, Discovery Sciences, AstraZeneca
Targeted Protein Degradation for Treatment of Cancer
Michael Plewe, PhD, Vice President, Medicinal Chemistry, Cullgen Inc.
Targeted Degradation of IRAK4 Protein Via Heterobifunctional Small Molecules for Treatment of MYD88 Mutant Lymphoma
Nan Ji, PhD, Executive Director, Head of Chemistry, Kymera Therapeutics
OVERCOMING EXISTING TRANSLATIONAL CHALLENGES
Translating Cellular Degradation Insights to In vivo Models
Stewart Fisher, PhD, CSO, C4 Therapeutics
Novel Strategies for Oncoprotein Degradation
Willem den Besten, PhD, Senior Scientific Researcher, Genentech
Antibody-Mediated Delivery of Protein Degraders
Peter Dragovich, PhD, Staff Scientist, Discovery Chemistry, Genentech
EXPLORING NEW APPROACHES & TARGETS
New Ubiquitin Ligases and Novel PROTAC Approaches
Tauseef R. Butt PhD, President and CEO, Progenra Inc.
E3 Ubiquitin Ligases for PROTACs Discovery
Matthieu Schapira, PhD, Principal Investigator, Structural Genomics Consortium and Associate Professor, Pharmacology & Toxicology, University of Toronto
* The program is subject to change without notice, due to unforeseen reason.