(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)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-cyanocyclopropanecarbonyl)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 VHL (von Hippel-Lindau) E3 ligase ligand designed for next-generation PROTAC (Proteolysis Targeting Chimera) research. As a synthetic VHL recruiter, this molecule features enhanced binding affinity and selectivity, combined with a robust linker-ready functional group, making it a valuable reagent for targeted protein degradation.

Mechanism

This compound functions by specifically binding to the VHL E3 ubiquitin ligase complex. Once incorporated as an E3 ligase ligand within a heterobifunctional PROTAC molecule, it recruits VHL to the target protein. This proximity facilitates the transfer of ubiquitin from the E2 conjugating enzyme to the substrate, tagging it for rapid degradation by the 26S proteasome. The precise stereochemistry and the cyanocyclopropanecarbonyl moiety ensure strong interaction with the VHL binding pocket, while the hydroxy group allows modular conjugation to a linker or payload.

Applications

(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)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 serves as a key building block in the development of VHL-based PROTACs and molecular degraders. Its applications include:

• Construction of PROTAC molecules for TPD (Targeted Protein Degradation) to investigate and drug challenging targets
• Synthesis of VHL-recruiting warheads for preclinical & academic research
• Structure-activity relationship (SAR) studies to optimize PROTAC efficacy and selectivity
• Medicinal chemistry campaigns focused on novel degrader design
• Custom synthesis pipelines for biotechnology, pharmaceutical, and CRO partners

With its high VHL recruitment capacity and convenient functionalization handle, this ligand accelerates the design and validation of next-generation targeted protein degraders.

• 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
• Optimized for targeting VHL E3 ligase, enabling efficient and selective protein degradation in PROTAC research.
• High purity and superior structural integrity ensure reliable results in drug discovery and development workflows.