Pre-Conference Focus Day
Tuesday 15 March 2022
Targeted Protein Degradation Assay Development
9:00 am Registration & Morning Coffee
9:25 am Chair’s Opening Remarks
Utilising Assays to Monitor Degradation, Find Molecular Glues & Successfully Match Assays to a Target
9:30 am High-Throughput Quantitative Assay Technologies for Accelerating the Discovery & Optimization of Targeted Protein Degradation Therapeutics
Synopsis
- Review of emerging technologies for higher throughput cellular assays amenable for TPD
- Advantages and disadvantages of fluorescent protein fusions and reporter tags, flow cytometry, TR-FRET and split luciferase systems for monitoring target degradation
- General strategies to accelerate targeted protein degradation drug discovery efforts
10:00 am Finding Degradation in a Haystack
Synopsis
- How to evaluate degradation
- What assays fill find the needle
- Is there a correct strategy to find a good degrader?
10:30 am De novo Identification of a Fully Synthetic FKBP12-FRB Molecular Glue
Synopsis
- Assays for the identification of molecular glues
- Structural and biophysical characterisation
- Guidelines for screening campaigns for molecular glues
11:00 am Structured Networking & Morning Refreshments
12:00 pm Identification of the Best Cellular Assay for Each Specific Target
Synopsis
- Outline of three different targets and approaches that were taken
Leveraging Innovation in Assay Development to Elevate Drug Design
12:30 pm Strategies for Controlling Entry to the Ubiquitin Proteasome Pathway
Synopsis
- Entry to the ubiquitin proteasome pathway is regulated at several levels
- Each decision point in the UPP is an opportunity for pharmacological intervention to control proteostasis
- Outlining the various possibilities and present two case studies from work in my lab on new ways to co-opt the UPP
1:00 pm Networking Lunch
2:00 pm Enabling Biochemical Methodologies for PROTACs
Synopsis
- Biochemical methods to identify new warheads for E3 ligases
- Quantitative methods for ternary complex formation
- In vitro ubiquitination assays
2:30 pm Assays to Monitor Targeted Degradation by Autophagy & the Proteasome
Synopsis
- Development of Autophagy Targeting Chimera
- Development of assays to monitor degradation of autophagy cargo and mitochondria
- Exploration of druggable targets in the autophagy pathway