Workshop B: Accelerating Molecular Glue Discovery: Capture & Prioritize Early Hits with Screening Cascades to Advance Effective Leads

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.