Kaila Nishikawa L&S Sciences
Developing Molecular Glue Degraders for Target Protein Degradation
Since the mid-20th century, the field of drug discovery for disease regulation has focused on the concept of occupancy-driven pharmacology. However, more than 90 percent of the proteome is currently deemed undruggable due to a lack of surface-lying ligandable hotspots. Many of these undruggable proteins, such as transcription factors and protein complexes, are implicated in disease but cannot be targeted through active site directed inhibitors, creating a need for new therapeutic modalities that can control protein function. One method for targeting undruggable proteins is through the use of molecular glue degraders, small molecules that chemically elicit target protein degradation. My project seeks to determine the essential chemical elements that define molecular glue degraders and use these findings to create guidelines for the creation of effective molecular glues. My project will make it easier to target disease-related proteins currently deemed undruggable by current pharmaceutical techniques.