VH 032, propargyl

Background Introduction

VH 032, propargyl is a specially designed E3 ligase ligand-linker conjugate based on the widely used VH032 moiety, optimized for use in PROTAC (Proteolysis Targeting Chimera) technologies. The incorporation of a propargyl group enables convenient chemical conjugation with target-binding ligands, greatly enhancing versatility in targeted protein degradation research. As PROTAC-based therapeutics are rapidly advancing in drug discovery, VH 032, propargyl serves as a crucial tool for scientists developing next-generation targeted therapies.

Mechanism

VH 032, propargyl functions as an E3 ligase ligand-linker conjugate by leveraging its high-affinity binding to the von Hippel-Lindau (VHL) protein, a key component of the VHL E3 ubiquitin ligase complex. The propargyl functional group enables bioorthogonal conjugation (commonly through click chemistry) to a ligand for a protein of interest. When incorporated into bifunctional PROTAC molecules, the VH 032 moiety recruits the VHL E3 ligase to the target protein, facilitating its ubiquitination and subsequent degradation via the proteasome pathway. This mechanism enables specific and efficient elimination of disease-causing or pathogenic proteins within cells.

Applications

VH 032, propargyl finds broad application in the development of PROTAC molecules for research and drug discovery. It is highly suitable for scientists seeking to assemble custom PROTACs against a variety of target proteins in oncology, neurodegenerative diseases, and other therapeutic areas. Additionally, VH 032, propargyl is invaluable for studying protein homeostasis, validating novel drug targets, and generating chemical biology tool compounds. Its propargyl group makes it compatible with a range of conjugation chemistries, supporting modular design strategies in medicinal chemistry and chemical biology projects.