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