Pomalidomide-PEG1-Alkyne

Background Introduction

Pomalidomide-PEG1-Alkyne is a versatile E3 ligase ligand-linker conjugate based on the immunomodulatory drug pomalidomide. It features a PEG1 spacer and a terminal alkyne functionality, making it suitable for click chemistry. As a key building block in targeted protein degradation technologies like PROTACs (Proteolysis Targeting Chimeras), this conjugate enables researchers to covalently attach E3 ligase ligands to ligands for protein targets.

Mechanism

Pomalidomide-PEG1-Alkyne operates by harnessing the well-characterized E3 ubiquitin ligase cereblon (CRBN), which is recruited by the pomalidomide moiety. The PEG1 linker provides optimal spatial orientation and solubility, while the alkyne group enables bioorthogonal conjugation via click chemistry to various targeting ligands. In a PROTAC molecule, this conjugate facilitates the proximity-induced ubiquitination and subsequent proteasomal degradation of the chosen protein target, thus allowing selective and catalytic protein knockdown.

Applications

This product is ideal for constructing custom PROTACs and molecular glues for targeted protein degradation studies. The alkyne handle allows efficient and specific ligation to azide-functionalized targeting moieties, enabling rapid library generation for drug discovery, mechanistic biology, and target validation research. Pomalidomide-PEG1-Alkyne is widely used in medicinal chemistry, chemical biology, and pharmaceutical research for the development of next-generation therapeutics and for exploring novel degradation-based intervention strategies.