PR PROTAC

PR PROTACs (Progesterone Receptor Proteolysis Targeting Chimeras) are a class of targeted protein degraders designed to selectively eliminate the progesterone receptor (PR) by hijacking the cellular ubiquitin-proteasome system. These bifunctional small molecules consist of a ligand that binds to the PR, a chemical linker, and a ligand that recruits an E3 ubiquitin ligase, such as Cereblon (CRBN) or Von Hippel-Lindau (VHL). By bringing the PR into close proximity with the E3 ligase, the PROTAC facilitates the polyubiquitination of the receptor, marking it for degradation by the 26S proteasome. This approach is being investigated primarily for the treatment of hormone receptor-positive breast cancer, where PR signaling is a key driver of tumor progression and resistance to existing endocrine therapies. Unlike traditional antagonists that only block receptor activity, PR PROTACs aim to completely deplete the protein, potentially offering a more effective therapeutic response. Research in this field is notably being advanced by the laboratory of Shaomeng Wang at the University of Michigan.

Other names

Progesterone receptor degraderPR degraderPR-targeting PROTAC