Monofunctional intermediates for ligand-dependent target protein degradation

Abstract

The present disclosure provides monofunctional synthetic intermediates for the preparation of small-molecule drug conjugates. Coupling the monofunctional synthetic intermediates of this disclosure with an inhibitor of a target protein of interest, e.g., an oncogenic protein inhibitor, e.g., a BET bromodomain inhibitor or MDM2 inhibitor, provides a heterobifunctional small-molecule that simultaneously binds the target protein and a ubiquitin ligase, enabling ubiquitination and degradation of the target protein.