Pomalidomide-PEG3-OH

Background Introduction

Pomalidomide-PEG3-OH is a synthetic E3 ligase ligand-linker conjugate widely utilized in the development of Proteolysis Targeting Chimeras (PROTACs). This compound features pomalidomide, a well-characterized cereblon (CRBN) E3 ligase ligand, covalently linked to a triethylene glycol (PEG3) spacer with a terminal hydroxyl group. The PEG3 linker provides optimal flexibility and solubility, making this conjugate a versatile building block for assembling innovative chemical probes and targeted protein degraders.

Mechanism

Pomalidomide-PEG3-OH operates as a bifunctional molecule in PROTAC technologies. The pomalidomide moiety binds selectively to the CRBN E3 ubiquitin ligase, a key component of the ubiquitin-proteasome system. The PEG3 linker, ending with a reactive hydroxyl group, enables straightforward conjugation to target protein ligands via esterification or other chemoselective coupling strategies. When incorporated into a PROTAC molecule, this conjugate facilitates the proximity-induced ubiquitination of the target protein, ultimately directing its proteasomal degradation and resulting in potent, selective, and catalytic removal of disease-related proteins.

Applications

Pomalidomide-PEG3-OH is widely used in the research and development of PROTACs for targeted protein degradation. Its primary applications include: (1) serving as a chemical handle in the synthesis of bifunctional molecules targeting a diverse range of disease-relevant proteins for therapeutic intervention in oncology, immunology, and neurodegenerative disorders; (2) enabling structure-activity relationship (SAR) studies to optimize linker length and flexibility in novel PROTAC designs; and (3) facilitating the creation of new chemical probes for the validation and investigation of protein function through selective degradation pathways. This makes Pomalidomide-PEG3-OH an essential component for academics and pharmaceutical companies pushing the frontiers of targeted protein degradation technologies.