(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-cyclopropylphenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-cyclopropylphenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide is a synthetic ligand specifically designed for the recruitment of the Von Hippel-Lindau (VHL) E3 ubiquitin ligase, a core component frequently utilized in PROTAC (Proteolysis Targeting Chimeras) technology. VHL-based ligands are widely recognized for their efficiency in targeted protein degradation (TPD) and have become foundational in the next-generation drug discovery platforms.

Mechanism

This VHL ligand selectively binds to the VHL E3 ubiquitin ligase complex, facilitating the recruitment of VHL to a protein of interest when linked via a suitable linker to a specific target ligand. The resulting bifunctional PROTAC molecule bridges the E3 ligase and the target protein, instigating ubiquitination and subsequent proteasomal degradation of the target. The compound's pyrrolidine core and optimized side chains ensure high affinity and specificity for the VHL complex, making it an effective tool for designing potent PROTACs.

Applications

This VHL ligand plays a vital role in the synthesis and optimization of PROTACs for targeted protein degradation. Key applications include:

• Design and construction of VHL-recruiting PROTACs in drug discovery, especially for 'undruggable' targets
• Structure-activity relationship (SAR) studies for fragment-based ligand optimization
• Validation of VHL-mediated degradation pathways and E3 ligase selectivity
• Custom syntheses in academic and contract research settings, enabling the development of chemical probes and next-generation therapeutics

Due to its robust binding and modular linker compatibility, this ligand is an essential building block in the growing field of targeted protein degradation.

• 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
• High affinity for VHL E3 ligase enables efficient target protein degradation in PROTAC applications.
• Optimized stereochemistry ensures selective and potent recruitment of VHL, maximizing PROTAC efficacy and specificity.