VH032 analogue-2

Background Introduction

VH032 analogue-2 is a structurally optimized small-molecule ligand designed to target the Von Hippel-Lindau (VHL) E3 ubiquitin ligase, a key player in the ubiquitin-proteasome system. Derived from the prototypical VHL ligand VH032, this analogue is engineered for improved synthetic accessibility, enhanced binding affinity, and increased chemical stability, making it an ideal building block for the rational design and construction of PROTACs (Proteolysis Targeting Chimeras) and targeted protein degraders.

Mechanism

VH032 analogue-2 functions by binding specifically to the VHL E3 ligase, thereby recruiting the VHL complex as part of the E3 ubiquitin ligase machinery. When conjugated via an appropriate linker to a ligand or inhibitor of a target protein, the PROTAC molecule brings the target protein into close proximity to the VHL E3 ligase. This proximity facilitates the transfer of ubiquitin moieties to the target protein, marking it for rapid recognition and degradation by the cellular proteasome system. The unique chemical design of VH032 analogue-2 allows for efficient incorporation into bifunctional PROTACs, ensuring optimal positioning and interaction between the E3 ligase and the target protein.

Applications

VH032 analogue-2 is widely utilized in cutting-edge drug discovery and chemical biology research related to targeted protein degradation. Its primary applications include:

• Serving as a crucial VHL-binding building block for PROTAC and molecular glue design
• Enabling the development of bifunctional degraders aimed at modulating disease-relevant proteins
• Facilitating structure-activity relationship (SAR) studies to optimize degrader efficacy, selectivity, and pharmacokinetic properties
• Supporting custom synthesis in both academic and industrial laboratories for the exploration of novel pharmaceutical modalities and personalized medicine platforms

VH032 analogue-2 is thus a valuable tool for researchers aiming to push the boundaries of targeted protein degradation and next-generation therapeutics.

• 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, enhancing PROTAC efficiency
• Well-suited for constructing stable VHL-based PROTACs targeting protein degradation applications