Pre-Conference Day

Rational design of molecular glues is more complex than traditional drug discovery, requiring stabilization of ternary complexes where binary binding can be weak. Limited structural data and current AI tools constrain predictive power, so most glues are still discovered empirically through cereblon-based libraries. This workshop will explore strategies to overcome these challenges, integrating computational predictions with experimental validation, improving ternary complex modelling, and expanding discovery beyond known E3 ligases.

Join this session to:

• Navigate the three-body problem and data gaps by leveraging ternary complex stabilization highlights the complexity of rational glue design and enables the identification of truly predictive design principles
• Overcome computational and AI limitations by applying advanced modeling toternary complex energetics and cooperativity allows researchers to prioritize compounds more efficiently and reduce wasted experimental effort
• Transform screening versus rational design by shifting from empirical approaches toward predictive platforms unlocks the potential to explore new E3 ligases and expand chemical space, accelerating the discovery of first-in-class molecular glues

This workshop is perfect for teams seeking practical insights into overcoming data gaps, optimizing ternary complexes, and expanding their experimental toolkit for novel molecular glues.

Identifying early molecular glue hits requires sensitive assays, as standard binding or inhibition tests often fail to capture functional activity. Capturing hits requires carefully designed biochemical, cell-based, and proteomics assays that reflect ternary complex formation and target degradation. While ternary complexes remain central to glue discovery, recent insights suggest that maximal stability is not always optimal for degradation. This workshop will explore strategies for implementing tiered

screening cascades, validating hits across multiple contexts, and considering target expression, E3 ligase availability, and multi-protein complexes to improve translation into downstream studies.

This workshop will gather experts to discuss:

• Capturing relevant hits using biochemical, cell-based, and proteomics assays detects transient PPIs and ternary complexes effectively
• Prioritizing meaningful candidates with tiered screening cascades to confirm degradation, selectivity, and mechanism while reducing false positives
• Accounting for biological context by considering target expression, E3 ligase availability, and multi-protein complexes and the dynamic nature of ternary interactions to improve translation in vivo

This session is designed for chemists, biologists, and translational scientists looking to optimize screening cascades and improve the reliability of early-stage hit selection.