(2S,4R)-N-[(1S)-1-(4-chlorophenyl)-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-chlorophenyl)-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. VHL is one of the most widely used E3 ligases in PROTAC (Proteolysis Targeting Chimera) research, making this compound valuable for targeted protein degradation strategies. This VHL ligand contains specialized linkable functional groups, enabling flexible conjugation for the design and synthesis of high-efficiency PROTACs.

Mechanism

This VHL ligand selectively binds to the VHL component of the CUL2-VHL E3 ubiquitin ligase complex. Upon binding, it recruits the ligase to proximity of a target protein (delivered via a tethered protein-targeting ligand), which facilitates the transfer of ubiquitin molecules to the target protein. This ubiquitination event signals for the rapid degradation of the targeted protein by the proteasome. The structural features of the ligand allow for robust and stable linker attachment, facilitating optimized PROTAC architectures with enhanced cellular activity and selectivity.

Applications

(2S,4R)-N-[(1S)-1-(4-chlorophenyl)-3-(methylamino)-3-oxopropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide is widely used as a VHL E3 ligase binding moiety in PROTAC and targeted degradation research. Common applications include:

• Development of VHL-based PROTACs for selective protein degradation and mechanistic studies
• Medicinal chemistry optimization of bifunctional degraders and linker SAR studies
• Construction of chemical probes for exploring protein function and disease-related targets
• Use in custom synthesis projects for academic, pharmaceutical, and biotechnology R&D focused on next-generation therapeutics

Its suitability for diverse linker attachment ensures compatibility with a wide range of target protein ligands, making it a go-to intermediate for PROTAC development and related targeted protein degradation technologies.

• 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 for efficient E3 ligase recruitment in PROTAC design.
• Optimized chemical structure supports robust targeted protein degradation with minimal off-target effects.