(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1R)-3-(methylamino)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-3-oxopropyl]pyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1R)-3-(methylamino)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-3-oxopropyl]pyrrolidine-2-carboxamide is a potent ligand specifically designed to recruit the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. VHL ligands have become a cornerstone in the development of PROTACs (Proteolysis Targeting Chimeras), which enable selective, catalytic degradation of target proteins in drug discovery and chemical biology. This advanced VHL ligand structure incorporates unique functional groups and stereochemistry, maximizing binding affinity and chemical flexibility for conjugation in degrader molecule design.

Mechanism

This compound operates by selectively binding to the VHL E3 ubiquitin ligase component. When linked through an appropriate linker to a ligand for a protein of interest, it forms a bifunctional molecule (PROTAC). The design ensures robust interaction with the VHL binding pocket, thus facilitating the recruitment of VHL to the target protein. This proximity triggers ubiquitination of the target, marking it for recognition and degradation by the proteasome. The incorporation of a fluorocyclopropanecarbonyl group and precise stereochemistry enhances ligand stability, affinity, and cellular permeability, crucial for efficient target degradation.

Applications

This VHL ligand is a valuable chemical tool in the synthesis of next-generation PROTACs and molecular glue degraders. Its robust binding and modular structure enable the rapid assembly of heterobifunctional molecules for research and therapeutic development. Key applications include:

• Construction of VHL-recruiting PROTACs for targeted protein degradation (TPD) platforms
• Drug discovery and validation of disease-relevant proteins by conditional knockdown
• Structure-activity relationship (SAR) studies to optimize degrader specificity and potency
• Custom synthesis for academic, biotech, and CRO research programs
• Application in chemical probes for mechanistic studies of ubiquitination and proteasome-mediated degradation

This compound plays a crucial role in advancing targeted protein degradation and opens new avenues for tackling previously undruggable proteins in pharmaceutical development.

• 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 E3 ligase ligand facilitates targeted protein degradation in PROTAC development.
• Optimized for high binding affinity and stability, ensuring efficient and reproducible PROTAC synthesis processes.