Molecular Glues - From Protein Degradation to Transcription Factor Reprogramming

This seminar from the Broad-MIT Seminar Series in Chemical Biology features Stanford University's Nathanael Gray discussing "Molecular Glues - from Protein Degradation to Transcription Factor Reprogramming." Explore how molecular glues—small molecules that exert pharmacological effects by inducing new protein-protein interactions—have experienced renewed interest in chemical biology. Learn about the development of a novel class of molecular glues targeting transcription factors, with specific focus on Bcl-6, a transcription factor critical to B-cell development that becomes an oncogene in lymphomas. Discover how Gray's team developed bivalent small molecules called transcription factor induced chemical inducers of proximity (TCIPs) that can convert Bcl6 from a transcriptional repressor to a potent activator of apoptotic cell death. The presentation demonstrates how these compounds modulate gene expression at picomolar concentrations and show efficacy in mouse models, providing proof-of-concept that transcription factors can be reprogrammed by molecular glues—opening therapeutic opportunities in oncology and other diseases.