(2S,4R)-N-[(1S)-1-(4-cyanophenyl)-3-(methylamino)-3-oxopropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-N-[(1S)-1-(4-cyanophenyl)-3-(methylamino)-3-oxopropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide is a potent and highly selective ligand for the Von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. VHL-based ligands, inspired by hydroxyproline derivatives, are essential building blocks for the design of VHL-recruiting PROTACs (Proteolysis Targeting Chimeras). These ligands facilitate precise protein degradation strategies in targeted protein degradation (TPD) research and drug discovery.

Mechanism

This compound specifically binds to the VHL E3 ubiquitin ligase by mimicking naturally occurring recognition motifs, particularly hydroxyproline-containing peptides. Upon conjugation to a ligand for the protein of interest through a suitable linker, this VHL ligand enables the formation of a ternary complex, bringing the E3 ligase into proximity with the target protein. This spatial orientation triggers ubiquitination of the target protein, leading to its degradation by the cellular proteasome. Its structural modifications, including the cyanophenyl and isoxazole groups, offer enhanced binding affinity, selectivity, and linker versatility for efficient PROTAC design.

Applications

(2S,4R)-N-[(1S)-1-(4-cyanophenyl)-3-(methylamino)-3-oxopropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide is especially valuable for:

• Synthesis of VHL-based PROTACs for targeted protein degradation in cellular and in vivo models
• Structure-activity relationship (SAR) analyses to optimize E3 ligase engagement
• Development of bifunctional degraders for disease-associated proteins, advancing small molecule drug discovery
• Generation of chemical probes to study protein function and protein-protein interactions in biological research

This ligand's versatility and strong binding profile make it an indispensable tool for academic research, pharmaceutical development, and custom PROTAC projects.

• 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 and specificity for VHL E3 ligase, enabling efficient targeted protein degradation in PROTAC design.
• Optimized structure for enhanced cellular permeability and bioavailability, supporting potent and selective therapeutic applications.