(2S,4R)-4-hydroxy-N-[(1S)-3-(methylamino)-3-oxo-1-phenylpropyl]-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-4-hydroxy-N-[(1S)-3-(methylamino)-3-oxo-1-phenylpropyl]-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide is a highly potent and selective ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase. The VHL ligase is a key component in the ubiquitin-proteasome system, responsible for the targeted degradation of hypoxia-inducible factors and a variety of neosubstrates when engaged by synthetic degraders such as PROTACs (Proteolysis Targeting Chimeras). VHL-based ligands like this compound are pivotal in drug discovery and targeted protein degradation research, enabling the rational design of next-generation therapeutics.

Mechanism

This compound binds specifically to the VHL E3 ligase complex. Upon conjugation to a ligand for a protein of interest via a suitable linker, it brings the target protein into close proximity with the VHL E3 ubiquitin ligase. This proximity induces the polyubiquitination of the target protein by the VHL complex, marking it for subsequent recognition and degradation by the cellular proteasome machinery. The stereochemistry and structural features of this VHL ligand confer high affinity, selectivity, and favorable pharmacological properties for efficient PROTAC assembly.

Applications

(2S,4R)-4-hydroxy-N-[(1S)-3-(methylamino)-3-oxo-1-phenylpropyl]-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide is widely utilized in PROTAC and targeted protein degradation research. Its applications include:

• Serving as a core VHL E3 ligase ligand for the synthesis of VHL-recruiting PROTACs
• Facilitating the development of bifunctional molecules for targeted protein degradation in oncology, neurology, and other therapeutic areas
• Supporting structure-activity relationship (SAR) studies and optimization of PROTAC degraders
• Enabling the design of customized molecular tools for target validation and mechanistic biology

This compound is ideal for academic research, CRO services, and pharmaceutical drug discovery aimed at leveraging the power of the ubiquitin-proteasome system for therapeutic protein knockdown.

• 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 for targeted protein degradation applications
• Crucial warhead for designing potent VHL-based PROTACs, enhancing efficacy and selectivity