Pomalidomide-PEG3-NH2 hydrochloride

Background Introduction

Pomalidomide-PEG3-NH2 hydrochloride is a versatile E3 ligase ligand-linker conjugate primarily used in the synthesis of PROTACs (Proteolysis Targeting Chimeras). This compound incorporates pomalidomide, an immunomodulatory agent well-known for binding to cereblon (CRBN), an E3 ubiquitin ligase. With a PEG3 (triethylene glycol) linker and an amine (NH2) functional group, Pomalidomide-PEG3-NH2 hydrochloride provides a flexible and hydrophilic scaffold for PROTAC design and customization.

Mechanism

Pomalidomide-PEG3-NH2 hydrochloride functions by recruiting the CRBN E3 ubiquitin ligase complex upon incorporation into a PROTAC molecule. The pomalidomide moiety specifically and effectively binds to the CRBN substrate recognition domain. The PEG3 linker offers enhanced solubility and spatial flexibility, aiding the bifunctional PROTAC in simultaneously binding the target protein and the E3 ligase. This proximity promotes ubiquitination and subsequent proteasomal degradation of the target protein, leading to its efficient downregulation within cells.

Applications

Pomalidomide-PEG3-NH2 hydrochloride is widely utilized in the rational design and synthesis of PROTAC molecules for targeted protein degradation research. Its applications include developing custom PROTACs for studies in oncology, neurodegeneration, and other disease models where protein degradation is a therapeutic strategy. The amine functional group enables straightforward conjugation with various target protein ligands via amide coupling or other chemistries, making this conjugate a valuable building block in academic, pharmaceutical, and biotech research environments focused on chemical biology and drug discovery.