(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-tert-butylphenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-tert-butylphenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide is a synthetic ligand designed to target the Von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, a popular platform for targeted protein degradation. As a VHL ligand, it serves as a critical component in the construction of PROTACs (Proteolysis Targeting Chimeras), driving research and innovation in the field of targeted protein degradation for both basic research and therapeutic applications.

Mechanism

This compound functions by precisely binding to the VHL E3 ubiquitin ligase, enabling the recruitment of this ligase to a specific target protein when conjugated via a suitable linker to the target-binding ligand in a PROTAC molecule. Upon formation of the ternary complex, the VHL ligase mediates ubiquitination of the target protein, leading to its recognition and rapid degradation by the cellular proteasome machinery. Its optimized chemical structure provides strong and selective VHL engagement, along with a functional handle for conjugation via the 4-hydroxypyrrolidine moiety, facilitating the development of effective and modular PROTACs.

Applications

(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[(1S)-1-(4-tert-butylphenyl)ethyl]-4-hydroxypyrrolidine-2-carboxamide is widely utilized in the discovery and development of VHL-based PROTAC molecules and protein degraders. Key applications include:

• Synthesis of bifunctional PROTACs for targeted degradation of disease-relevant proteins
• SAR (structure-activity relationship) studies in medicinal chemistry programs aiming to optimize degrader efficacy and selectivity
• Development of tool compounds for target validation and mechanism-of-action studies in cellular and in vivo systems
• Custom CRO projects for designing and synthesizing novel VHL ligase binders and linkable intermediates

This ligand is essential for researchers focusing on next-generation therapeutics, drug discovery, and advanced biological research utilizing the protein degradation platform.

• 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 and potent VHL ligand enables efficient recruitment of the E3 ubiquitin ligase complex.
• Optimized stereochemistry and functional groups make it ideal for developing next-generation PROTAC degraders targeting a wide range of proteins.