Azido-Thalidomide

Background Introduction

Azido-Thalidomide is a highly versatile E3 ligase ligand-linker conjugate designed for use in the development of PROTACs (Proteolysis Targeting Chimeras). As a derivative of thalidomide containing an azide functional group, it facilitates modular construction of targeted protein degradation tools for research and drug discovery.

Mechanism

Azido-Thalidomide functions as a cereblon (CRBN) E3 ubiquitin ligase ligand, harnessing the ubiquitin-proteasome system for selective protein degradation. Its azide group enables bioorthogonal ‘click chemistry’ conjugation with a variety of alkyne-modified ligands, allowing rapid and flexible assembly of heterobifunctional PROTAC molecules. Once incorporated into a PROTAC, the thalidomide-based moiety binds to CRBN, recruiting the E3 ligase complex to a target protein, resulting in ubiquitination and proteasomal degradation of the target protein.

Applications

Azido-Thalidomide is ideal for chemical biology and drug discovery applications, particularly in the design and synthesis of next-generation PROTAC molecules. It is widely used for structure-activity relationship (SAR) studies, rapid prototyping of targeting chimeras, functional screening of protein degradation, and validation of novel therapeutic targets. Additionally, it supports the development of custom protein degraders in cancer, neurodegenerative disease, and immunology research.