Pomalidomide-PEG5-NH2 hydrochloride

Background Introduction

Pomalidomide-PEG5-NH2 hydrochloride is a specialized E3 ligase ligand-linker conjugate commonly utilized in the design and synthesis of PROTACs (Proteolysis Targeting Chimeras). This compound features pomalidomide—a well-documented cereblon (CRBN) ligand—connected via a five-unit polyethylene glycol (PEG5) linker to an amino group, forming a versatile molecular tool for targeted protein degradation strategies in chemical biology and drug discovery research.

Mechanism

The mechanism of Pomalidomide-PEG5-NH2 hydrochloride centers on its role as an E3 ligase recruiter within PROTAC molecules. The pomalidomide moiety binds selectively to the cereblon (CRBN) E3 ubiquitin ligase, while the PEG5 linker confers flexibility and optimal spatial orientation for linkage to a ligand directed against a target protein. Upon binding, the bifunctional PROTAC brings the target protein into proximity with CRBN, promoting ubiquitination and subsequent proteasomal degradation of the target protein. This event-driven mechanism enables selective, catalytic elimination of disease-relevant proteins.

Applications

Pomalidomide-PEG5-NH2 hydrochloride is widely employed in the development and study of PROTACs and other heterobifunctional molecules for targeted protein degradation. Applications include: (1) Chemical biology research to probe protein function by targeted knockdown; (2) Preclinical drug discovery efforts to assess the tractability of undruggable targets; (3) Synthesis of customized PROTACs by conjugation to specific targeting ligands; and (4) Validation of cereblon-recruiting linker designs for optimizing cellular activity and drug-like properties. Its use accelerates the development of next-generation therapeutics in oncology, neurodegeneration, and autoimmune disease research.