(2S,4R)-N-[(1S)-1-(4-ethynylphenyl)-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-ethynylphenyl)-3-(methylamino)-3-oxopropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide is a highly specialized ligand designed to bind to the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. VHL ligands are widely used in the development of PROTACs (Proteolysis Targeting Chimeras) for their strong specificity and efficient induction of target protein degradation. This compound incorporates a functionalizable 4-ethynylphenyl group, enabling flexible linker attachment for custom PROTAC assembly.

Mechanism

This VHL ligand acts by engaging the VHL E3 ubiquitin ligase through high-affinity binding. When conjugated to a target protein ligand via a suitable linker, it forms a bifunctional PROTAC molecule. The PROTAC simultaneously brings the target protein and the VHL E3 ligase into proximity, facilitating ubiquitination of the target protein. This tagged protein is then recognized and degraded by the proteasome, resulting in selective, catalytic protein knockdown within cells.

Applications

This VHL E3 ligase ligand is highly valuable for designing and synthesizing VHL-recruiting PROTAC molecules and molecular glues. Its ethynyl functional group provides a convenient chemical handle for linker attachment, broadening its utility in customized PROTAC development. Key applications include:

• Construction of VHL-based PROTACs for targeted protein degradation studies
• Development of tool compounds for target validation and mechanism exploration
• Medicinal chemistry programs focused on SAR optimization and degrader enhancement
• Synthesis of advanced VHL ligands for academic and pharmaceutical drug discovery efforts

• 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
• Highly selective VHL ligand enables precise E3 ligase recruitment in PROTAC design
• Facilitates efficient protein degradation for advanced targeted protein knockdown research