Pomalidomide-PEG2-OH

Background Introduction

Pomalidomide-PEG2-OH is a cutting-edge E3 ligase ligand-linker conjugate designed to facilitate the development of PROTACs (Proteolysis Targeting Chimeras). This compound integrates pomalidomide, a well-characterized cereblon (CRBN) E3 ligase ligand, with a PEG2 (polyethylene glycol) linker terminated with a hydroxyl (-OH) group, providing versatile functionality for downstream chemical conjugation. As PROTACs continue to revolutionize targeted protein degradation, linker-payload conjugates like Pomalidomide-PEG2-OH are essential building blocks in the creation of next-generation therapeutics.

Mechanism

Pomalidomide-PEG2-OH operates as an E3 ligase-recruiting module in bifunctional molecules such as PROTACs. Pomalidomide selectively binds to the CRBN substrate receptor within the CUL4 E3 ubiquitin ligase complex. The PEG2 linker provides optimal spatial flexibility, allowing the terminal -OH group to be further coupled to a ligand that binds the target protein of interest (POI). Once a PROTAC is assembled using this conjugate, it enables the simultaneous recruitment of the E3 ligase and the POI, facilitating ubiquitination and subsequent proteasomal degradation of the target.

Applications

Pomalidomide-PEG2-OH finds widespread use in the design and synthesis of PROTAC molecules for targeted protein degradation. Researchers use this conjugate to create custom PROTACs against disease-relevant targets in oncology, neurology, and beyond. Its structure ensures reliable CRBN engagement while providing a functional handle for linking novel target ligands. The product streamlines the drug discovery process by simplifying PROTAC construction, supporting SAR (Structure-Activity Relationship) studies, and enabling rapid prototyping of degrader compounds in biological assays.

• Hydrophilic PEG2 linker improves solubility and pharmacokinetic properties in PROTAC development.
• Pomalidomide-based E3 ligase ligand ensures high affinity CRBN recruitment for effective target protein degradation.