Molecular Glue (MG) Discovery: Current Challenges and Paths Forward
9:00 am - Tuesday 26th January 2027
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
