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

Background Introduction

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-chlorophenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide is a highly specialized ligand designed to target the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. VHL-based ligands are essential for the construction of PROTACs (Proteolysis Targeting Chimeras), which harness the cellular ubiquitin-proteasome system to selectively degrade disease-related proteins. This compound offers improved potency and selectivity for VHL, providing a robust foundation for the synthesis of next-generation protein degraders.

Mechanism

This VHL ligand binds specifically to the VHL E3 ligase, forming a ternary complex when linked to a suitable ligand for a protein of interest. Upon binding, the VHL ligase facilitates the transfer of ubiquitin moieties from an E2 enzyme to the targeted protein, marking it for rapid degradation by the 26S proteasome. The stereochemistry and functional groups of this ligand ensure high affinity and optimal orientation, maximizing the efficiency of ubiquitination and degradation and enabling precise control in PROTAC-mediated targeted protein degradation.

Applications

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-chlorophenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide is widely used as a VHL E3 ligase ligand in PROTAC research and drug discovery. Its applications include:

• Building VHL-based PROTACs for targeted protein degradation in oncology, neurology, and immunology.
• Facilitating the design of bifunctional degraders for validation of new protein targets.
• Supporting structure-activity relationship (SAR) studies to optimize PROTAC efficacy and selectivity.
• Serving as a key intermediate in medicinal chemistry and custom synthesis for academic and pharmaceutical research.

This ligand's potency and modularity make it an excellent tool for advancing targeted protein degradation strategies and next-generation therapeutic development.

• 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
• Selective VHL ligand offers high affinity and specificity for E3 ligase recruitment in PROTAC development.
• Optimized chiral structure enhances stability and bioavailability, making it suitable for potent and precise protein degradation research.