Workshop Day

Tuesday April 26, 2022

All times in EDT

9.00-11.00

Workshop A: Expanding the Toolbox for Drug Discovery of E3 Ligases & Substates

Harnessing ligases for therapeutic application has emerged as a modality with great potential and has begun to expand the landscape modulating and degrading previously undruggable targets. Despite this, the landscape of discovered and targetable ligases that have been exploited for therapeutics remains limited, and a large portion of E3 ligases remain undiscovered and uncharacterized. With advanced technologies, this industry is generating data and expanding the toolbox for how we can target E3 ligases and proteins of interests. As we aim to progress this therapeutic modality, it is critical that we generate a knowledge base and generate a large amount of targetable and hijackable ligases.

In this session, we will consider:

Tools and technologies currently being employed by leaders of the ligase community to expand the existing landscape of hijackable ligases
How we can share experiences harnessing complex tools to expand the library of ligases
Lessons learned from chemical biology and drug discovery informing how human E3 ligases can expand the toolbox for PROTAC discovery

Workshop Leaders:

Smaranda Bodea
Associate Principal Scientist
Chemical BiologyMerck Research Laboratories

Benjamin Ruprecht
Director of Translational Proteomics
Roivant Sciences

12.00-2.00

Workshop B: Revealing the Characterization of Ligase Complexes & the Kinetics of Ubiquitination

Understanding the structural and kinetic features of the ternary complexes formed by ligase and substrate are critical to the ability to harness for therapeutic application. This industry is maximizing biophysical techniques to study the structure, properties, dynamics and function of ligases, leveraging approaches such as cryoEM and crystallography. Through a deep dive into the various techniques that leaders of the industry are employing, we can truly understand what makes an efficient degradation machinery complex for therapeutic application.

In this session, we will consider:

The various biophysical tools and techniques that are being harnessed by the industry, and how these are being employed to uncover critical structural and kinetic information into ubiquitin ligases
How insights from these tools are informing critical decisions
How we can harness mathematical modelling in conjunction with the data gained to guide discovery and development of an effective ligase based therapeutic

Workshop Leaders:

Rick Deibler
Senior Research Scientist II
C4 Therapeutics

Roman Agafonov
Senior Research Scientist II
University of Nevada, Las Vegas

3.00-5.00

Workshop C: Ensuring Optimal Safety & Toxicology Profiles of Drugs Leveraging E3 Ubiquitin Ligases

Discovering drugs to target a specific E3 ligase are suggested to have high selectivity and low associated toxicity, making ubiquitin ligases a highly valuable therapeutic modality. Despite this, there are still concerns questions surrounding the safety, toxicity and pharmacology with harnessing E3 ligases for degradation and modulation. With this, it is important to review these learnings from both molecular glues and bi-functional degraders to guide early discovery and development of E3 ligase-based drugs, to ensure optimal safety and toxicology, and advance E3 ligases degraders and modulators through development.

In this session, we will consider:

The learnings from proteomics which can guide early ligase-based drug discovery and future drug development
Reviewing what this data can tell us about translation into clinic and if this poses inherent challenges-what will be the bottleneck for progression

Workshop Leaders: