(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-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-[(1S)-3-(methylamino)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-3-oxopropyl]pyrrolidine-2-carboxamide is a potent and selective ligand designed to engage the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. The VHL ligase has become a foundational building block in targeted protein degradation technologies, including PROTACs (Proteolysis Targeting Chimeras). This advanced VHL ligand is characterized by high binding affinity, structural tunability, and compatibility for linker attachment, making it exceptionally useful for constructing efficient and selective VHL-based degraders.

Mechanism

This VHL ligand binds specifically to the VHL E3 ligase component of the CUL2-VHL E3 ubiquitin ligase complex. When incorporated into a bifunctional PROTAC molecule, it recruits the VHL ligase to a target protein that is simultaneously bound by a target-specific ligand. The resulting proximity facilitates ubiquitin transfer to the target protein, marking it for recognition and rapid degradation by the proteasome. Strategic placement of a reactive handle or linker site allows facile conjugation to various target protein ligands, giving researchers flexibility to design and optimize PROTAC constructs.

Applications

This VHL E3 ligase ligand is a cornerstone molecule for the development of VHL-based PROTACs and molecular glue degraders. Its specific applications include:

• Synthesis of PROTACs targeting diverse disease-relevant proteins for chemical biology and early-stage drug discovery
• Structure-activity relationship (SAR) studies to optimize target degradation efficiency and selectivity
• Development of molecular glues that induce protein-protein interactions and targeted degradation via the VHL pathway
• Tool compound generation for E3 ligase biology research and target validation
• Custom linker-strategy design for academic and pharma-based PROTAC projects

Overall, this VHL ligand is essential for researchers seeking high-performing and readily modifiable building blocks in targeted protein degradation 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
• Designed for high-affinity binding to VHL E3 ligase, optimizing targeted protein degradation efficiency in PROTAC applications.
• Features excellent aqueous solubility and chemical stability, facilitating seamless incorporation into advanced bifunctional degraders.