Potential for E3 Ligase Binders

The discovery of novel E3 ligases provides new targets for small molecule binding. E3 ligases play a crucial role in protein degradation and are attractive targets for drug development.

Interplay Bio can leverage our screening technology to:

• Identify small molecules that specifically bind to these novel E3 ligases
• Develop compounds that modulate E3 ligase activity
• Create a library of E3 ligase binders for further drug discovery efforts

Molecular Glue Development

Molecular glues are compounds that induce protein-protein interactions, often leading to targeted protein degradation.

The polypharmacology identified in our screening provides an excellent starting point for molecular glue development:

• The diverse set of identified interactions (E3 ligases, SUMO E3 ligase, deubiquitinases) offers multiple potential protein partners for glue formation
• Small molecules binding to these enzymes can be optimized to induce proximity with other proteins
• The screening technology can be adapted to identify compounds that simultaneously bind to multiple proteins, a key characteristic of molecular glues

Leveraging Polypharmacology

The identification of multiple targets within related pathways (ubiquitination, SUMOylation, deubiquitination) through a single screening effort demonstrates the power of polypharmacology in this approach.

This can be exploited to:

• Develop compounds with multiple mechanisms of action
• Create more effective degraders by targeting multiple components of the ubiquitin-proteasome system
• Fine-tune the balance between protein modification and degradation for therapeutic benefit
  

Interplay Bio has identified two novel E3 ligases, one SUMO E3 ligase, and two deubiquitinases demonstrating the power and specificity of our screening platform.

Interplay's success in discovering previously unknown enzymes in the ubiquitin pathway suggests:

• The technology can detect a wide range of protein-small molecule interactions
• It is sensitive enough to identify novel members of protein families
• The screening library contains diverse compounds capable of interacting with these enzyme classes