Pomalidomide-PEG6-NH2 hydrochloride

Background Introduction

Pomalidomide-PEG6-NH2 hydrochloride is a versatile E3 ligase ligand-linker conjugate designed for modern PROTAC (Proteolysis Targeting Chimera) drug discovery and development. This compound combines the immunomodulatory drug pomalidomide—an established cereblon (CRBN) E3 ubiquitin ligase ligand—with a hydrophilic, flexible PEG6 linker terminated by a primary amine group in its hydrochloride salt form. Such conjugates have become essential building blocks for next-generation targeted protein degradation tools and related research applications.

Mechanism

Pomalidomide-PEG6-NH2 hydrochloride works by taking advantage of the PROTAC mechanism. The pomalidomide moiety selectively binds to the cereblon (CRBN) E3 ubiquitin ligase, while the PEG6 linker offers optimal spatial flexibility to connect to other functional small molecules or protein-targeting ligands. Once the complete PROTAC molecule is formed and introduced into a cell, it simultaneously binds the target protein and the CRBN E3 ligase, forming a ternary complex. This proximity induces ubiquitination of the target protein, earmarking it for degradation by the cell's proteasome system, and thereby allowing for the selective removal of disease-related or pathogenic proteins.

Applications

Pomalidomide-PEG6-NH2 hydrochloride is widely used in the synthesis of custom PROTACs and molecular glues targeting various proteins implicated in cancer, neurodegenerative diseases, and immune disorders. Researchers leverage its CRBN-binding and linker properties to rapidly create libraries of bifunctional degraders for screening or lead optimization. Additionally, the primary amine functionality enables flexible coupling chemistries, expanding its utility for attaching diverse ligands or payloads in chemical biology, drug discovery, and target validation studies. Its role in advancing targeted protein degradation therapies continues to drive innovation in translational research and pharmaceutical development.