Pomalidomide-PEG4-C-COOH

Background Introduction

Pomalidomide-PEG4-C-COOH is a versatile E3 ligase ligand-linker conjugate widely employed in the development of PROTACs (Proteolysis Targeting Chimeras). This molecular tool combines pomalidomide, a well-known cereblon (CRBN) E3 ligase ligand, with a PEG4 spacer and a carboxylic acid terminal group for streamlined conjugation. The product enables researchers to efficiently design and synthesize targeted protein degraders for advanced therapeutic research.

Mechanism

The mechanism of action relies on the ability of pomalidomide to bind with high affinity to the CRBN E3 ubiquitin ligase component. Pomalidomide-PEG4-C-COOH serves as a modular building block, where the PEG4 linker provides optimal spatial flexibility and solubility. The carboxylic acid (C-COOH) group at the terminus is chemically reactive, facilitating the attachment to a ligand for a protein of interest via amide bond formation. When conjugated, the PROTAC molecule simultaneously recruits the target protein and CRBN, promoting ubiquitination and subsequent proteasomal degradation of the target.

Applications

Pomalidomide-PEG4-C-COOH is ideal for the rational design and synthesis of cereblon-recruiting PROTACs, molecular glues, and related protein degradation technologies. It is extensively used in drug discovery and chemical biology to induce selective degradation of disease-associated proteins, enabling target validation and preclinical research in oncology, neurodegeneration, and beyond. With its ready-to-conjugate carboxylic acid group and flexible PEG4 chain, this E3 ligase ligand-linker conjugate is a valuable tool for generating customized degraders, accelerating the development of next-generation therapeutics.