Pomalidomide 4'-PEG3-azide

Background Introduction

Pomalidomide 4'-PEG3-azide is a specialized E3 ligase ligand-linker conjugate frequently used in the design and synthesis of PROTACs (Proteolysis Targeting Chimeras). By fusing the immunomodulatory drug pomalidomide, a CRBN (Cereblon) E3 ligase recruiter, with a PEG3 linker terminating in an azide group, this product provides high utility and versatility in targeted protein degradation research and drug discovery.

Mechanism

The mechanism of action for Pomalidomide 4'-PEG3-azide centers on its bifunctional properties. The pomalidomide moiety selectively binds the CRBN E3 ubiquitin ligase complex, while the PEG3-azide linker enables bio-orthogonal click chemistry, facilitating conjugation with various ligands that target proteins of interest. Once incorporated into a PROTAC molecule, this conjugate enables the proximity-induced ubiquitination of the target protein, leading to its recognition and subsequent degradation via the proteasome pathway.

Applications

Pomalidomide 4'-PEG3-azide is primarily used in the synthesis of CRBN-based PROTACs and molecular glues for targeted protein degradation. The terminal azide allows for efficient, modular assembly of PROTACs using click chemistry, accelerating the rapid design of custom degraders against oncogenic proteins, transcription factors, or other disease-related targets. Additionally, it is valuable for chemical biology studies, drug screening platforms, and research in cellular signaling pathways where precise protein knockdown is desired.