(2S,4R)-N-[(1S)-1-(4-bromophenyl)-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-bromophenyl)-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 VHL (Von Hippel-Lindau) E3 ligase ligand commonly utilized in the design of PROTACs (Proteolysis Targeting Chimeras). The VHL E3 ligase is a crucial component of the cellular ubiquitin-proteasome system (UPS) that plays a central role in protein homeostasis and targeted protein degradation. This ligand is functionalized for efficient conjugation, making it an ideal starting block for constructing bifunctional degrader molecules.

Mechanism

This compound binds specifically to the VHL E3 ubiquitin ligase complex through high-affinity interactions, primarily driven by its structurally optimized hydroxyproline core and complementary functional groups. When incorporated into a PROTAC molecule, (2S,4R)-N-[(1S)-1-(4-bromophenyl)-3-(methylamino)-3-oxopropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide tethers the target protein to the VHL E3 ligase, facilitating ubiquitination and subsequent proteasomal degradation. Its design allows for robust, site-specific linker attachment, supporting precise and efficient degrader synthesis.

Applications

This VHL ligand is widely employed in PROTAC research and protein degradation technology development, including:

• Synthesis of VHL-based PROTACs for targeted protein knockdown
• Drug discovery and development focused on undruggable targets
• Validation of novel biological pathways via induced proximity degradation
• Medicinal chemistry, structure-activity relationship (SAR) studies, and optimization of bifunctional molecule libraries
• Collaboration with CROs and academic groups for custom synthesis of protein degraders

Its modular structure supports a variety of conjugation strategies, making it suitable for high-throughput screening, target validation, and next-generation therapeutics design.

• 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
• Potent and selective VHL E3 ligase ligand enables efficient target protein ubiquitination in PROTAC research.
• Optimized for constructing high-affinity, cell-permeable PROTACs, facilitating targeted protein degradation studies.