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

  • Jeffrey Simard Associate Director, Cell Pharmacology, C4 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

3:00 pm Chair’s Closing Remarks & End of Pre-Conference Focus Day