<br/>Proximity-based strategies to degrade proteins have revolutionized biomedicine, but the technology remains confined to proteins for which small molecule ligands exist. However, a large subset of the remaining “undruggable” human proteome engages in interactions with other biomolecules. Herein I describe our efforts in leveraging these interactions to create ligands that can be used as the protein-targeting moieties in bifunctional degraders. As a proof-of-principle, we demonstrate the degradation and subsequent functional modulation of a transcription factor with relevance to the beta-hemoglobinopathies and triple-negative breast cancer. This work establishes a new paradigm to target previously intractable proteins with cell-permeable, biomolecule-based degraders.

Chemical tools for expanding the “druggable” proteome

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.