VH032-cyclopropane-F

Background Introduction

VH032-cyclopropane-F is a high-affinity ligand derivative of VH032, a landmark molecule that targets the von Hippel-Lindau (VHL) E3 ubiquitin ligase. Engineered with a cyclopropane ring and a fluorine atom, this compound offers increased metabolic stability and improved binding properties, making it invaluable for the assembly of VHL-based PROTACs (Proteolysis Targeting Chimeras). The innovative linker architecture of VH032-cyclopropane-F facilitates efficient conjugation to target ligands, streamlining the creation of advanced molecules for targeted protein degradation.

Mechanism

VH032-cyclopropane-F functions by specifically binding to the VHL E3 ligase, a key component of the CUL2-RBX1 E3 ubiquitin ligase complex. When incorporated into a PROTAC structure, this ligand enables the recruitment of VHL to a chosen target protein. The resulting ternary complex (target protein-PROTAC-VHL) promotes ubiquitination of the target via the ubiquitin-proteasome pathway, ultimately leading to its selective degradation. The tailored cyclopropane and fluorine modifications enhance ligand binding affinity and chemical robustness, supporting high-efficiency PROTAC design.

Applications

VH032-cyclopropane-F serves as an essential building block for the development of VHL-based PROTACs and other protein degraders. Its optimized properties make it highly suitable for:

• Synthesis of bifunctional degraders for targeted protein knockdown in cells
• Medicinal chemistry and structure-activity relationship (SAR) studies on VHL ligase recruitment
• Drug discovery programs aimed at novel therapeutic modalities for undruggable targets
• Custom development of molecular glues and tool compounds for mechanistic studies

VH032-cyclopropane-F is widely utilized in both academic and industrial settings, accelerating research in targeted protein degradation and the next generation of therapeutic strategies.

• 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, enabling efficient target protein degradation in PROTAC applications.
• Incorporates a cyclopropane-linked fluorine group for enhanced metabolic stability and improved pharmacokinetic properties.