(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-(4-propan-2-ylphenyl)ethyl]pyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-(4-propan-2-ylphenyl)ethyl]pyrrolidine-2-carboxamide is a structurally optimized ligand recognized for its high affinity toward the Von Hippel-Lindau (VHL) E3 ubiquitin ligase. VHL ligands are central tools in the PROTAC (Proteolysis Targeting Chimera) field, enabling the recruitment of VHL to mediate targeted protein degradation. This molecule incorporates key functional groups that ensure high selectivity and potent ligase engagement, which are essential for the development of next-generation protein degraders.

Mechanism

This VHL ligand operates by specifically binding to the VHL E3 ligase complex, a pivotal player in the ubiquitin-proteasome pathway. When incorporated into a bifunctional PROTAC molecule, it brings the VHL E3 ligase into close proximity with a target protein by connecting via a chemical linker to a ligand for the desired target. This induced proximity facilitates the ubiquitination of the target protein, marking it for recognition and rapid degradation by the 26S proteasome. The unique stereochemistry and functional groups present in the ligand promote stable E3 ligase interaction and optimal PROTAC performance.

Applications

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-(4-propan-2-ylphenyl)ethyl]pyrrolidine-2-carboxamide is a premium chemical building block for constructing VHL-based PROTACs and targeted protein degraders. Its applications include:

• Synthesis of bifunctional molecules for targeted protein degradation utilizing VHL as the recruited E3 ligase
• Structure-activity relationship (SAR) studies focused on optimizing PROTAC efficacy and selectivity
• Chemical biology research exploring the mechanistic aspects of E3 ligase recruitment
• Development of therapeutic candidates and chemical probes for drug discovery

This compound is widely employed in academic research, CRO service projects, and pharmaceutical pipelines concentrating on targeted proteomics and innovative small molecule degrader strategies.

• 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 specifically designed for effective E3 ubiquitin ligase recruitment in PROTAC development.
• Optimized molecular structure enables robust target protein degradation, supporting advanced drug discovery and research workflows.