(2S,4R)-1-((S)-17-Amino-2-(tert-butyl)-4-oxo-6,9,12,15-tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

Background Introduction

(2S,4R)-1-((S)-17-Amino-2-(tert-butyl)-4-oxo-6,9,12,15-tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide is a highly specialized small molecule designed for targeted protein degradation research. As a novel E3 ligase ligand-linker conjugate, this compound plays a vital role in the development of Proteolysis Targeting Chimeras (PROTACs) for chemical biology and drug discovery. Its unique structure allows seamless integration with a variety of target binding ligands, making it a versatile tool in the field of targeted protein degradation.

Mechanism

This E3 ligase ligand-linker conjugate works by selectively recruiting an E3 ubiquitin ligase to a protein of interest when tethered to a target binding moiety. The ligand portion specifically binds an E3 ligase, while the attached linker provides chemical flexibility and distance optimization for subsequent PROTAC assembly. When incorporated into a bifunctional PROTAC molecule, this conjugate brings the E3 ligase in close proximity to the target protein, facilitating ubiquitination and subsequent proteasomal degradation. This mechanism effectively removes disease-relevant proteins from cells in a highly selective manner.

Applications

(2S,4R)-1-((S)-17-Amino-2-(tert-butyl)-4-oxo-6,9,12,15-tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide is widely used in the synthesis of customized PROTACs for target validation, mechanism-of-action studies, and preclinical drug discovery. Researchers employ this conjugate to expand the toolbox for targeted protein degradation by designing new PROTACs with improved cell permeability and selectivity. It is an essential building block for developing novel therapeutic strategies against cancer, neurodegenerative diseases, and other pathologies where traditional inhibitors fall short.