Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules.

ABSTRACT: Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among TPD approaches, proteolysis-targeting chimeras (PROTACs) have shown marked advancement, with numerous candidates in clinical development. Despite their potential, most PROTACs utilize advanced small-molecule inhibitors, inherently limiting the scope of this approach. More generally, the fraction of the proteome tractable to small-molecule-induced degradation strategies is unknown. Here we describe a chemical proteomic strategy for the agnostic discovery of degradable proteins in cells using a new class of bifunctional degrader molecules called "AgnoTACs". Proteome-wide screening of 72 AgnoTACs

SUBMITTER: Forrest I 

PROVIDER: S-EPMC12670307 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature