VH032 analogue-1

Background Introduction

VH032 analogue-1 is a derivative of VH032, a well-established small-molecule ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. The VHL ligase plays a pivotal role in cellular protein homeostasis by targeting hypoxia-inducible factors (HIFs) and other substrates for ubiquitination and proteasomal degradation. VH032 analogue-1 has been structurally optimized to enhance binding affinity, solubility, and linker compatibility, making it a valuable building block for the development of VHL-based PROTACs (Proteolysis Targeting Chimeras).

Mechanism

VH032 analogue-1 functions as a high-affinity ligand for the VHL E3 ubiquitin ligase complex by binding to the hydroxyproline-binding pocket of the VHL protein. When incorporated into a PROTAC molecule as the E3 ligase recruiting moiety, VH032 analogue-1 mediates the formation of a ternary complex between VHL, the PROTAC, and the target protein. This promotes ubiquitination of the target protein by the VHL complex, marking it for rapid degradation via the ubiquitin-proteasome pathway. The optimized linker attachment point on VH032 analogue-1 facilitates the design of PROTACs with optimal molecular orientation and degradation efficiency.

Applications

VH032 analogue-1 is widely utilized in the rational design and synthesis of VHL-based PROTACs for targeted protein degradation. Its enhanced properties make it suitable for medicinal chemistry, SAR studies, and structure-guided PROTAC optimization. Key applications include:

• Development of VHL-recruiting PROTACs to degrade proteins implicated in cancer, neurodegenerative diseases, and immune disorders
• Construction of bifunctional degraders and molecular glues for chemical biology research
• Structure-activity relationship (SAR) explorations to optimize degrader potency, selectivity, and pharmacokinetics
• Custom synthesis projects for CROs, pharmaceutical companies, and academic laboratories pursuing targeted protein degradation technologies.

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Optimized for high-affinity binding to VHL E3 ligase, ensuring efficient target protein degradation in PROTAC applications
• Structurally designed for versatile conjugation, facilitating the creation of diverse PROTAC molecules for research and drug discovery