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

Background Introduction

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-cyanophenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide is a highly specific and synthetically accessible ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase. VHL is one of the most frequently employed E3 ligases in the design and development of PROTAC (Proteolysis Targeting Chimera) molecules, which have emerged as a revolutionary modality in targeted protein degradation and drug discovery. This compound features enhanced selectivity and binding affinity toward VHL, making it an ideal building block for advanced degrader design.

Mechanism

This compound acts as a VHL E3 ligase recruiter by specifically binding to the VHL protein, a critical component of the CUL2-VHL E3 ubiquitin ligase complex. When linked to a ligand targeting a protein of interest via a chemically customizable linker, this molecule brings the target protein into proximity with VHL. This proximity enables the polyubiquitination of the target protein, which is subsequently recognized and degraded by the 26S proteasome machinery. The highly functionalized pyrrolidine and cyano-phenyl substructures facilitate strong and selective VHL engagement, ensuring efficient target degradation in PROTAC systems.

Applications

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-cyanophenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide is widely used in the development of VHL-based PROTACs for targeted protein degradation. Its robust VHL-binding profile, synthetic flexibility, and linker compatibility make it a cornerstone for:

• De novo PROTAC design and synthesis in drug discovery pipelines
• Validation and exploration of novel protein targets through induced degradation
• Modulation of disease-relevant proteins in cancer, neurodegeneration, and immunology research
• Structure-activity relationship (SAR) optimization and medicinal chemistry campaigns
• Utilization in CRO and academic research for constructing next-generation degraders

• 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 VHL ligand supports targeted and efficient E3 ligase recruitment in PROTAC development.
• Optimized stereochemistry enhances selectivity and potency for reliable protein degradation applications.