(2R,3S,4S)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Background Introduction

(2R,3S,4S)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide is a highly specialized ligand designed for recruiting the Von Hippel-Lindau (VHL) E3 ubiquitin ligase. As part of the rapidly advancing field of targeted protein degradation, this compound serves as a critical E3 ligase ligand for constructing PROTACs (Proteolysis Targeting Chimeras) and other heterobifunctional degraders. VHL-based ligands provide an orthogonal approach to more commonly used CRBN ligands, enabling the selective degradation of disease-relevant proteins in drug discovery and research settings.

Mechanism

This compound functions as a high-affinity ligand for the VHL E3 ligase complex. By binding to the VHL protein, it acts as the E3 ligase-recruiting moiety in bifunctional PROTAC molecules. When chemically linked to a ligand that targets a protein of interest, the resulting PROTAC brings the target protein into close proximity with the VHL ligase, promoting target ubiquitination and subsequent recognition and degradation by the cellular proteasome system. Key features such as the fluorine and 4-hydroxy substitutions contribute to increased binding affinity and metabolic stability, optimizing its performance in degrader applications.

Applications

(2R,3S,4S)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide is ideal for a range of research and drug discovery projects focusing on targeted protein degradation. Main applications include:

• Synthesis of VHL-based PROTACs to induce selective degradation of oncoproteins, transcription factors, and other disease-associated targets.
• Medicinal chemistry and structure-activity relationship (SAR) studies to design optimized molecular degraders.
• Development of novel chemical probes to validate protein targets in cellular and animal models.
• Custom synthesis for academic, pharmaceutical, and CRO research initiatives focused on targeted protein degradation platforms.

• 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 specific VHL E3 ligase ligand for targeted protein degradation applications, enhancing selectivity in PROTAC design.
• Fluorine and thiazole modifications improve binding affinity and metabolic stability, supporting efficient and reliable PROTAC development.