Conference Day 2
8:50 am Chair’s Opening Remarks
New Technologies to Discover Novel E3 Ligases Continued
9:00 am Presenting a Chemoproteomic Platform for Identifying Covalent Small Molecule Ligands of Novel E3 Ligases
Synopsis
- Harnessing the unique advantages of covalent small molecule ligands of E3 ligases
- Showcasing how IMTAC-screening can quickly identify covalent small molecule ligands of novel E3 ligases in a live cell screening
- Demonstrating effective covalent ligand identified by IMTAC using an established ligase assay
9:30 am Measuring the Tractability of E3 Ligases for Informed Drug Discovery
Synopsis
- Discussing the tractability of different ligase classes and how this will impact downstream drug development
- Recruiting new substrates to ‘hijack’ an E3 ligase with a small molecule with views towards degradation
- Weighing up whether a BRD4 model system is the best model system moving forward
Validation & Optimization
Diving Deeper Into the 600+ Known Ligases, Do We Need to Know More?
10:00 am PANEL DISCUSSION: Beyond CRBN – Enrichment of PK Optimized E3 Ligase Recruiters for TPD
Synopsis
- Developing of targeted small molecule libraries against multiple high-value E3 ligases with Asha’s PRISM platform
- Exploring the use of these novel E3 ligase recruiters in Asha drug discovery pipeline for beta Catenin, KRAS, and MEK
- Spotlighting a novel, non-peptide, PK optimized, small molecule for VHL and uses beyond oncology
10:30 am Morning Break & Poster Session
11:30 am What More Can We Get Out of the Established Ligases, Cereblon & VHL
Synopsis
- How do we propel VHL from an ‘academic’ ligase to a viable clinical alternative to CRBN?
- Are there lessons to be learned from years of CRBN work that can be applied to future novel e3 ligase discovery and development?
12:00 pm Examining the Molecular Basis for Recognition of the Degrons by Novel E3 Ligases
Synopsis
- Uncovering the E3 ligases that promote ubiquitin change and modifications that are not directing targets to the proteome
- Characterizing the biology in non-integrative processes and E3s that do not direct localization of substrates
Utilizing the Role of Tissue-Tumor & Cell Type-Specific Ligases
12:30 pm PANEL DISCUSSION: Tissue & Cell Selectivity – Debating the Potential for Selective E3 Targeting
Synopsis
- What is the hurdle to targeting E3s specifically in tumor cells and tissue types?
- How can specific degradation be induced within a specific tissue type, limiting off-target effects?
- What is the importance and use of expression data for our understanding and insight to develop tissue and cell-specific E3 therapeutic?
1:15 pm Networking Lunch
2:15 pm Showcasing a Rational Approach to Tissue-Specific E3 Ligase Discovery
Synopsis
- Outlining the current limitations in available technologies to explore and identify tissue and cell-specific ligases
- Presenting an example of useful omic data showing ligase tissue specificity
- Selecting the correct ligand for cell-specific studies when little is known about the endogenous ligand
2:45 pm Identifying Novel E3 Ligases for Targeted Protein Degradation
Synopsis
- Examining considerations of E3 ligase selection for targeted protein degradation
- Using small molecule-induced proximity to assess E3 ligase activity
- Debating the current limitations in technologies to explore tissue and cell-specific ligases
Investigating Rational Design & Exploring Future Potential of E3 Ligases
3:15 pm Highlighting an Approach to Uncovering a Novel E3 Ligase to Bolster your Ligase Discovery Pipeline
Synopsis
- Reviewing the structural biology of the novel ligase
- Elucidating the novel ligase mode of action
- Outlining opportunities for translation to the clinic
3:45 pm Afternoon Networking Break
4:15 pm Mapping E3 – Leveraging Target Protein Interactions to Guide Molecular Glue Discovery
Synopsis
- Measuring interactions between E3 ubiquitin ligases and targets of interest in the absence of any small molecule to find pairs that bind weakly
- Generating E3 ligase/target binding data with AlphaSeq, a synthetic biology platform that utilizes yeast display for high-throughput and highly sensitive measurements of up to millions of protein-protein interactions
- Showcasing data that provide significant insights into the glueability of novel interactions between E3 ligases and high-value therapeutic targets
4:45 pm Chair’s Closing Remarks
5:00 pm End of Conference
All times in EDT