Focus Day

Tuesday April 26, 2022

This focus day unites the ligase community to discuss and share their current progress and understanding of ubiquitin ligase biology, as well as delving into how we can utilise critical insights of ligase structure and function to guide optimal design of therapeutics harnessing E3’s. Through fully understanding ubiquitin ligase biology, structure and function, we can truly maximize ligase targeting therapeutics for the treatment of human diseases. Take part in this deep-dive focus day and hear from the leading minds as they take us through valuable biological and structural insights, for you to take back to your team.

All times in EDT

9:00 am Registration Opens & Welcome Coffee

9:50 am Chair’s Opening Remarks

  • Matt Clifton Director Structural & Biophysical Chemistry , Novartis institutes for Biomedical Research

10:00 am Chemically Harnessing Novel E3 Ligase Biology for Next-generation TPD Therapeutics

  • Lewis Pennington Senior Director, Head of Platform Chemistry, Kymera Therapeutics

Synopsis

  • Identifying small molecule ligands for novel E3 ligases
  • Developing heterobifunctional degraders for targeted POIs
  • Evaluating pharmacology for cellular proof-of-concept efforts

10:30 am Mechanistic Diversity of E3 Ligases

  • Satpal Virdee MRC Investigator & Professor of Chemical Biology, MRC Protein Phosphorylation & Ubiquitylation Unit, University of Dundee

Synopsis

  • Technology development for advancing E3 ligase research
  • The unexpected mechanistic diversity of E3 ligases
  • Therapeutic opportunities presented by newly discovered E3 ligases

11:00 am Morning Break & Structured Networking

12:00 pm Therapeutic Approaches to Targeting Parkin E3 Ub Ligase

Synopsis

  • Parkin Ligase regulates pathways critical to cellular health and is highly validated target
  • Small Molecule Drug Discovery has revealed significant challenges for Parkin
  • Detailed understanding of Parkin enzymology and biology is critical for Drug Development

12:30 pm Structure-Guided Design of Small Molecule Covalently targeting SH2 Domain of the E3 Ligase SOCS2

  • Sarath Ramachandran Senior Drug Discovery Scientist , Centre for Targeted Protein Degradation, University of Dundee

Synopsis

• We report structure guided design and development of potent phosphotyrosine-based covalent binders targeting the SH2 domain of SOCS2
• The covalent binder is structurally and biophysically characterised
• Cellular target engagement assay to demonstrate permeability and potency of the binder

1:00 pm Lunch & Networking Break

2:00 pm Targeted Protein Degradation Using Ubiquitin Variant Induced Proximity

  • Wei Zhang Assistant Professor, University of Guelph

Synopsis

  • We devised structure-based combinatorial protein design and engineering strategies to develop Ub variant (UbV) activators for human E3 ligases
  • We assembled a UbV induced proximity (UbVIP) library for targeted protein degradation
  • We identified UbVIPs that successfully induced intracellular degradation of nucleus substrates

2:30 pm Subtle Modification of Solvent-Exposed Moiety Confers Molecular Glue Activity for Targeted Protein Degradation

  • Hojong Yoon Postdoctoral Associate, Broad Institute of MIT & Harvard/Dana-Farber Cancer Institute

Synopsis

  • Review the design and development of molecular glues through the successful harnessing of E3 ligases
  • Small-molecule-induced target protein polymerization that leads to subsequent degradation

3:00 pm Chair’s Closing Remarks

  • Matt Clifton Director Structural & Biophysical Chemistry , Novartis institutes for Biomedical Research

3:15 pm End of Pre-Conference Focus Day