Pre-Conference Workshop Day

Molecular glues hold promise to tackle high value protein targets and to unlock novel therapeutics. Mechanistically, molecular glues can reprogram protein function by stabilizing native protein interactions or creating neomorphic complexes that drive inhibition, activation, or degradation. However, prospective molecular glue discovery remains challenging because of uncertainty around protein-pair “glue-ability,” limited ability to identify weak and rare screening hits, coupled with complex three-body thermodynamics, nonlinear SAR, and in certain cases biological constraints. This workshop will discuss the key challenges associated with molecular glue discovery and optimization, in addition to how mathematical models can be used to integrate biochemical and cellular data to assess MG binding kinetics, cooperativity, performance, and provide rational, testable guidance for MG design.

• Understand key challenges around MG discovery and optimization
• Explore mathematical modelling-guided design principles
• Discuss practical paths toward more rational molecular glue discovery

For many organizations, identifying a molecular glue hit is only the first hurdle. Determining whether that hit is mechanistically meaningful, clinically relevant, and worth the significant investment required for optimization remains one of the field’s greatest challenges. Researchers increasingly recognize that no single screening technology is sufficient, leading to growing adoption of DELs, functional screening, in-cell discovery platforms, proteomics, and biophysical characterization methods. This workshop will examine how to construct robust screening and profiling cascades that distinguish genuine opportunities from false positives, establish confidence in mechanism of action, and support more informed go/no-go decisions throughout molecular glue discovery.

Join this workshop to:

• Compare DEL, functional, cellular, proteomic, and next-generation screening approaches to identify productive induced-proximity events and expand discovery beyond traditional cereblon-based degradation
• Design multi-parameter profiling cascades that evaluate cooperativity, selectivity, mechanism of action, and biological relevance using biophysical tools, proteomics, and disease-relevant cellular models