Stephen Hinshaw
Senior Scientist Stanford University
Stephen is a senior research scientist in the Center for Therapeutics Discovery and at the Stanford Cancer Institute. At Stanford, his work focuses on using chemically induced proximity to discover powerful new pharmacology. He also drives challenging medicinal chemistry projects focused on high-value clinical targets. Before this, he was an undergraduate at Stanford and received a Ph.D. at Harvard from the Program in Genetics and Genomics, where he made contributions to the fields of cohesin biology and chromosome organization. After this, Stephen was a Helen Hay Whitney Postdoctoral Fellow supported by the Howard Hughes Medical Institute at Harvard Medical School, where he used cryo-EM to determine the molecular structures of protein complexes that underlie genetic inheritance in normal and cancerous cells.
Seminars
Identifying early molecular glue hits requires sensitive assays, as standard binding or inhibition tests often fail to capture functional activity. Capturing hits requires carefully designed biochemical, cell-based, and proteomics assays that reflect ternary complex formation and target degradation. While ternary complexes remain central to glue discovery, recent insights suggest that maximal stability is not always optimal for degradation. This workshop will explore strategies for implementing tiered
screening cascades, validating hits across multiple contexts, and considering target expression, E3 ligase availability, and multi-protein complexes to improve translation into downstream studies.
This workshop will gather experts to discuss:
- Capturing relevant hits using biochemical, cell-based, and proteomics assays detects transient PPIs and ternary complexes effectively
- Prioritizing meaningful candidates with tiered screening cascades to confirm degradation, selectivity, and mechanism while reducing false positives
- Accounting for biological context by considering target expression, E3 ligase availability, and multi-protein complexes and the dynamic nature of ternary interactions to improve translation in vivo
This session is designed for chemists, biologists, and translational scientists looking to optimize screening cascades and improve the reliability of early-stage hit selection.
- Explore innovative strategies to harness non-Cullin-based degradation mechanisms for targeted protein degradation
- Leverage structural insights to improve prediction accuracy and guide rational discovery of novel ligase-glue pairs
- Understand how bold discovery strategies and broader search spaces can accelerate breakthroughs in molecular glue therapeutics
