(2S,4R)-1-[(2R)-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-[(2R)-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 ligand utilized for recruiting the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex in targeted protein degradation applications. VHL ligase ligands are essential building blocks in the design and synthesis of PROTACs (Proteolysis Targeting Chimeras). This compound features structural motifs optimized for high affinity, selectivity, and chemical stability, advancing the development of next-generation targeted protein degraders.

Mechanism

This VHL ligand binds specifically to the VHL E3 ubiquitin ligase, facilitating the formation of an E3-substrate complex when tethered to a ligand for a protein of interest via an appropriate linker. The ternary complex formed enables VHL to transfer ubiquitin molecules onto the target protein, marking it for proteasomal degradation. The inclusion of specialized groups, such as the 1-fluorocyclopropanecarbonyl and 4-hydroxypyrrolidine motifs, enhance binding efficiency and chemical compatibility for PROTAC assembly.

Applications

This VHL E3 ligase ligand is widely used in the creation of VHL-based PROTACs, supporting a range of applications, including:

• Rational design and synthesis of bifunctional degraders targeting disease-relevant proteins
• Drug discovery platforms exploring undruggable or challenging targets
• Chemical biology research to elucidate protein function through selective degradation
• Medicinal chemistry optimization and SAR studies on tertiary VHL ligands
• Academic and pharmaceutical research for the validation of therapeutic targets

Its high-affinity interaction with the VHL E3 ligase makes this compound a preferred choice for developing efficient and selective targeted protein degradation tools.

• 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
• Potent and selective VHL E3 ligase ligand enables efficient ubiquitination and targeted protein degradation.
• Highly optimized for incorporation into PROTAC molecules for customizable targeted therapy development.